ADHD is neurodevelopmental disorder which persists into adulthood. Presently, therapeutic approaches are mainly pharmacological and psychological whilst the role, scope and approaches of occupational therapists have not been adequately described.In this consensus statement we propose that by assessing specific aspects of a person’s occupation, occupational therapists can deploy their unique skills in providing specialist interventions for adults with ADHD. We also propose a framework with areas where occupational therapists can focus their assessments and give practice examples of specific interventions.Occupational therapists have much to offer in providing interventions for adults with ADHD. A unified and flexible approach when working with adults with ADHD is most appropriate and further research on occupational therapy interventions is needed. Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder with a pooled worldwide prevalence estimated at approximately 5% in school-aged children. The symptoms of childhood ADHD are found to persist in adulthood in up to 65% of cases, leading to a prevalence of the condition in that population to be approximately 2.5% .Attention-deficit hyperactivity disorder (ADHD) is characterised by clinical impairment in the areas of inattention and/or hyperactivity–impulsivity  and is aMany adults with ADHD and are used to their lifelong symptoms, have a limited awareness of how ADHD adversely affects their life; some report higher symptoms but lower impairments or vice versa and this may affect diagnostic accuracy. Also, adult diagnoses may be missed in clinical practice due to lack of knowledge about ADHD in adulthood among practitioners and due to the high frequency of comorbid psychiatric conditions .If an adult receives a diagnosis of ADHD, the treatment options open to them which are supported with robust evidence base is either or a combination of pharmacological or psychological . DespiteThe consensus aimed to provide practical guidance to occupational therapy professionals working with adults with ADHD, drawing on the scientific literature and the professional experience of the authors. To achieve this aim, professionals specialising in ADHD convened in London at expert workshop called “Occupational Therapy and Adult ADHD” on the 10th February 2017. The event was hosted by the UK Adult ADHD Network (UKAAN). UKAAN is an organisation founded in 2009 by a group of mental health specialists in response both to the NICE guidelines  , academic, educational and occupational specialists. Attendees engaged in discussions throughout the day, with the aim of reaching consensus.The day was structured around presentations on pre-selected topics of interest by invited experts, followed by a discussion after each presentation aiming to reach a consensus position on the topic. At the end of the day, there was a summary presentation of the points previously agreed and further discussion.Recovery approaches in adult ADHD.AHP into action: A Strategic Framework and OpportunityOccupational Therapists as Healthcare Professionals: roles, expertise, skills, future developments in the professions.Adult ADHD: implications for O/T interventionsPraxis difficulties in adult ADHDSensory integration difficulties in adult ADHDThe meeting started with a review of the status of non-pharmacological interventions in adult ADHD to set the scene. Then experts presented the following topics:The consensus group incorporated evidence from a broad range of sources. All consensus proceedings were audio-recorded and transcribed.Allied Health Professionals (AHPs) are health care professionals distinct from nursing, medicine, and pharmacy . They arA recent strategy developed to inform and inspire the healthcare system about how AHPs can be best utilised to support key healthcare transformation initiatives  suggest To deliver this work, the AHPs have entered into four commitments  and four priorities . Occupational Therapists are essential members of AHP group and committed to support the strategic objectives and priorities so their impact and contribution in the wider healthcare system is enhanced.The ability to synthesise and apply occupational concepts is what uniquely distinguishes occupational therapy from other health professions , 12. TheOccupational therapy practice emphasises the occupational nature of humans and the importance of occupational identity . It provThis support increases people’s independence and satisfaction in all aspects of life. “Occupation” as a term refers to practical and purposeful activities that allow people to live independently and have a sense of identity , 17. ThiOccupations are central to a person’s identity and sense of competence and have particular meaning and value to that individual. Occupational therapists are skilled in evaluating all aspects of the domain, their interrelationships, and the client within his or her contexts and environments Table . Originaeducational functioning [relationships [ADHD affects all aspects of Occupational Functioning: In terms of Client Factors, people with ADHD report low self-esteem  and selfctioning  with stuctioning  and overctioning –26. Simiionships  and therionships  which caionships  and loneionships .employment, there is evidence to imply poor performance; for example, young adults with ADHD were shown to change employment frequently, obtain fewer full time occupations and be more frequently fired [In terms of Performance Patterns, referring to ly fired . Similarly fired .Another study estimated that adult ADHD was associated with a 4–5% reduction in work performance, a 2.1 relative-odds of sickness absence and a 2.0 relative-odds of workplace accidents and injuries . A surveA possible explanation why these Contexts and Environments are affected, may be due to the cognitive impairment which has been documented in ADHD which leads to Performance Skills impairment. We know that both vigilance and sustained attention are impaired in adults with ADHD  so it isOne of the well documented deficits in ADHD is to their executive function; this is what allows an individual to plan a series of steps necessary to achieve a desired goal, keep these steps in mind whilst acting on the goal, monitor progress through these steps, and have the cognitive flexibility to adjust or change the steps if progress is not being made toward the original goal . In adulApart from deficits in attention and executive function, children  and adulOccupational therapists have skills and competencies unique in understanding and affecting change in adult ADHD which affects many domains of a person’s occupation. Although the theoretical case can be made, there is need for further research to evidence the effects for occupational therapy interventions in adult ADHD.Best practice requires that therapists thoughtfully choose the models that fit their views of the purpose and focus of therapy, as well as support their ability to understand and explain the specific challenges faced by their clients . “The thInterventions for ADHD are mainly focused on how symptom reduction can be achieved with either Medicines or Psychological Interventions . HoweverFrom previous work, we found that the framework proposed by the ADHD Star can be a useful guide to multidisciplinary interventions based on the ADHD Star domains ‘Focus and Attention’, ‘Friends and Social Life’, ‘Physical Health’, ‘How you Feel’ “Understanding your ADHD”, “Organising yourself”, “Thinking and reacting” and “Meaningful use of time” . To thisInterventions consider what the therapist and client identify to work on during a treatment session. Interventions are defined from the Occupational Therapy Practice Framework [Preparatory methods are techniques that prepare a client to participate in occupations and for our purpose can be a discussion and completion of the ADHD Star. Purposeful activities suggest that the client participate in activities that help improve skills that would enhance occupational performance, such as gardening, joining a social group, doing voluntary work etc. Occupation-based intervention is when a client, in therapy, engages in occupations that match his or her identified goals, which may include cooking in a kitchen, getting dressed in his or her room, and travelling independently. Observations are made on how the therapist describes the interventions to the client and if they relate to the client’s goals. The Occupational therapist will use a graded approach and adapt the demands of the occupation, the environmental context or the support provided to maximise independence, skill acquisition and self-efficacy.ramework  and inclIn considering which intervention approaches to recommend for ADHD, we used our clinical experience and the strategies suggested by Fleming  to solveWe propose that occupational therapy for adults with ADHD should focus on the following:1. Organising and adapting the physical and /or social environment to enable participation 2. Promoting social awareness and interactions within occupations 3. Encouraging self-management of symptoms through strategies such as sensory regulation, stress management techniques, adaptations to routines.The fact that treatment environments influence a client and their performance has been known for many years . In the For example, a common phenomenon of ADHD is an inability to organise one’s physical environment to support daily functioning. Adults with ADHD frequently report that their physical environment such as their workplace, homes, car interior and personal belongings  are very untidy and that despite their efforts to organise or maintain their physical environments over prolonged period, their attempts are not successful. Occupational Therapist led interventions can help individuals understand that organisation requires regular, repeated behaviours rather than just one singular attempt. Creating structure, establishing routines and assigning places for essential items are often key to maintaining organisation. Occupational Therapists can use their unique skills to help establish behavioural change to support organisation, for example: having regular set times to sleep, eat and leave for work.Not having set times for these activities can lead to an unstructured and disorganised day. Occupational therapists can also introduce colour-coded label systems to allow for easy identification and location of items, and work with the individual to create file and record systems to store important documentation, such as utility bills or medical appointments. This reduces the clutter from a physical space, as well as allowing for easy access to these documents.Social interactions of people with ADHD are often impaired. For example children with ADHD are reported to have problems with peer relations , are lesDuring social interaction, the person with ADHD already operates within a sense of personal capacity  developing a planned schedule for each day, (b) adhering to the schedule being mindful that distractions can affect one’s plans, and (c) understanding when it might be appropriate to exercise flexibility once a schedule is decided. In a reactive mode, people would allow distractions to alter their adherence to a schedule, take up activities based on which one arises last without completing any and just let someone else to organise their daily schedule. In this reactive mode, people just live managing daily crises. Learning to structure their life in a planned mode, rather than impulsively reacting to events as they arise is a critical skill for adults with ADHD along with the ability to remain calm and stop and think before reacting. It may take time to help adults with ADHD learn that every situation does not require immediate attention or response, and that prioritising daily demands can be a useful stress management skill.To achieve a planned mode, adults with ADHD need to develop new familiar and automatic aspects of daily life through a process of habituation. Habituation is defined as an internalised readiness to exhibit consistent patterns of behaviour guided by our habits and comes about as a consequence of repeated patterns of behaviour under certain temporal, physical and sociocultural contexts  OccupatiADHD has been associated with poor time perception –82 and iSensory Integration theory links neurological processes to functional behaviour, whereby sensations from within an individual’s body and their environment are processed to enable them to participate in everyday life. Successful Sensory Integration is an adaptive process and follows when information from several of the senses travels into the brain to be processed. There is evidence that children with ADHD have sensory sensory processing problems  and the Occupational therapists can help adults with ADHD to recognise the relationship between mood, performance, and sensory stimulation; and learn to monitor and regulate the amount and type of sensory stimulation that enters their nervous system at any one time. The latter skill involves the concept of a sensory diet–or the ideas that one’s day is comprised of many different types of sensory experiences that can have a cumulative effect, and that people have unique sensory requirements that must be met to function optimally in all occupational domains . For exaOccupational therapists have much to offer in providing interventions for adults with ADHD. They are part of a unique group of professionals outside medicine, nursing and psychology with much to offer in delivering care. Occupational therapists have a unique undersdanding of the human as an occupational being and are able to rely on established models of practice. Currently, the evidence base for adults with ADHD is still being developed and this consensus statement aims to bridge that gap by providing practical recommendations for the jobbing occupational therapy on how to approach ‘what works’ for this service user group.What we propose is a unified and flexible approach when working with adults with ADHD. It is already known that for adults with ADHD to engage with activities these need to be perceived as inspiring, include an apparent goal to stimulate performance and need facilitating support . What ouWe also identified a need for occupational therapists to conduct research into the proposed consensus-based areas of intervention to better demonstrate the efficacy of their approach.


Introduction: Emotional fluctuations and mood swings are common among adults with Attention Deficit/Hyperactivity Disorder (ADHD). Here we investigated if these problems could be retrospectively traced back to childhood behavior.Methods: Adults with an ADHD diagnosis  and a population-based control sample  completed the Adult ADHD Self-report Scale (ASRS), the Wender Utah Rating Scale (WURS) and the Mood Disorder Questionnaire (MDQ). All participants also provided self-reported information about co-existent psychiatric and somatic diseases, and demographic data. Reports on the MDQ were used to define subgroups with [MDQ(+)] and without [MDQ(–)] life-time periods of emotional fluctuations and the WURS scale was used to retrospectively assess childhood ADHD related behaviors and symptoms.Results: 50.2% of the ADHD group and 5% of the controls were defined with emotional fluctuations [MDQ(+)]. Childhood behavior ratings of “impulsivity,” “loosing of control,” and “trouble with authorities” independently predicted emotional fluctuations reported in adulthood via logistic regression analyses. Inclusion of these three items in a classification analysis gave an accuracy score around 70% in identifying each of the two MDQ categories in the ADHD group.Discussion: The strong association between self-reported features of emotional problems in childhood and in adulthood suggests a trajectory that should be detected and remediated at an early age. Future longitudinal studies should prioritize the examination of developmental mechanisms explaining the persistence of emotional problems from childhood into adulthood. Attention-deficit/hyperactivity disorder (ADHD) is a childhood neurodevelopmental disorder characterized by impairing symptoms of inattention and/or hyperactivity/impulsivity that persist across situations and time  and adulthood (defined from MDQ scores) as reported by adults with an ADHD diagnosis and by a control sample recruited from the general population. From the information referred to above we had the following hypotheses: (1) A large proportion of the ADHD group would give reports on the MDQ indicating periods of emotional fluctuations [MDQ(+)]; (2) adults defined as MDQ(+) would show greater functional impairments as evidenced by lower educational success, higher current ADHD symptoms, and more co-occurring psychiatric disorders than the ADHD group not reporting emotional fluctuations [MDQ(–)]; (3) childhood behavior reflecting emotional fluctuations will be identified as predictors of emotional fluctuations in adulthood; and (4) the predictors of emotional fluctuations in the ADHD group would also be relevant in the control group, but will probably comprise more common mood related problems than in the ADHD group.http://www.uib. No/kgj-npd) where most of the participants in the ADHD group were recruited from a national registry of adults diagnosed in Norway from 1997 to May 2005. All participants had a formal diagnosis of ADHD before enrolled in the present study. Participants were diagnosed according to national guidelines recommended by expert teams according to the ICD-10 research criteria  defined according to the following criteria: seven or more answers of “yes” on the first 13 symptom items, “yes” on the next question (co-occurrence of symptoms), and at least a moderate impairment (“3 or more”) on the last item assessing impairment  reported information about gender, age, education, current occupational status, if they had been diagnosed with ADHD as a child and if they were diagnosed with dyslexia, a co-existent somatic disease  or other psychiatric disorders , or bipolar disorder]. The lifetime presence of co-existent disorders were assessed via self-reported answers to yes/no questions . None of the participants reported ID. A “yes” answer on the question: “Have you ever experienced significant anxiety or depression?” was used as a proxy for lifetime presence of anxiety/depression. The life-time presence of somatic disease was defined when at least one of the abovementioned diseases was reported to ever have been present.t-tests for continuous variables or chi-square tests for dichotomous variables). Logistic regressions were used to identify independent predictors associated with MDQ(±) classifications. All dichotomous variables were factorized, and the dispersion parameter for binominal family was set to be one. Two preparatory steps were performed, separately for the ADHD and the control group and with the MDQ classifications as the outcome variable. First, we included potential covariates  to eliminate covariates without significant unique contributions. Secondly, we included all the 25 dichotomized WURS variables as independent variables to select the ones with unique contributions to the MDQ- categorizations within the ADHD and the control group, respectively. The selected WURS and control variables were then included in four models, two for each group. Finally, we ran a classification analysis to investigate the prediction accuracy from the selected WURS items in the present sample.Version 3.3.2 of the R statistical program  was used for the statistical analyses, including descriptive exploratory analyses and group comparisons , of whom 74% (n = 53) were males. In the ADHD group, males reported higher scores than females on the MDQ-13 scale , while females reported higher scores on the total ASRS score  and the inattention  and hyperactivity/impulsivity  subscales. In the control group, males reported higher scores on the WURS scale  and a higher frequency of somatic diseases  = 3.374, p = 0.004] than males, while males showed higher scores on the MDQ-13 scale .In the ADHD group, about half of the adults were classified to the MDQ(+) category. Compared to those classified to the MDQ(–) category, participants in the MDQ(+) category showed lower education, reported more occupational difficulties, higher prevalence of a lifetime presence of anxiety/depression and BSD, and they obtained significantly higher scores on all the included symptom scales see . Within t(41.771) = 7.522, p < 0.001] and its two subscales (p < 0.001), the WURS  and the MDQ-13 .In the control group, only 5% of the adults were classified to the MDQ(+) category, with a balanced gender distribution. The controls classified in the MDQ(+) category showed a lower education level, a higher frequency of somatic diseases, dyslexia, and lifetime presence of anxiety/depression than the controls classified to the MDQ(–) category. The differences between the two MDQ categories were statistically significant both for the ASRS . Classification into these MDQ categories was explained by slightly different childhood symptoms in the ADHD and control groups; items reflecting childhood “impulsivity,” “loosing of self-control,” and “trouble with authorities” were unique contributors in the ADHD group, whereas being “angry, “irritable,” and having “trouble with authorities” contributed uniquely to the classification of controls. Among the control variables, lifetime presence of anxiety/depression had a significant unique contribution to explain allocation to the MDQ categories in both groups, while gender and symptoms of hyperactivity/impulsivity was added in the ADHD group and symptoms of inattention in the control group. The accuracy of predictions of MDQ category from the variables with unique contributions in the ADHD group was around 70%.The severity of emotional fluctuations should be emphasized. Its presence was defined when an adult reported ≥ 7 impairing symptoms. A prevalence of 50% in the ADHD group corresponds to the 50.6% with features of a BSD as reported by Halmøy et al.  from parThere are several noteworthy results from our study. The main contribution was provided by identification of childhood behavior predicting the emotional fluctuations reported in adulthood. By this, one may speculate that some of the WURS items could be seen as a childhood version of the MDQ. The “impulsivity” and “loosing of self-control” reported from childhood overlapped well with the core features of “emotional impulsivity” and “dysfunctional self-control” described by Barkley . AccordiThe core childhood predictors identified by the logistic regression analyses did also show some interesting similarities and differences between the ADHD and the control group. Although the unique contribution of childhood “impulsivity” was restricted to the ADHD group, reports on the impulsivity item provided high odds for being classified to the MDQ(+) category in both groups. In the control group, this was found together with very high odds from being “angry” as a child and having “trouble with authorities.” Taken together, these results indicate that at least some adults reporting lifetime emotional fluctuations in our sample may have shown symptoms associated with behaviors frequently seen in childhood ODD. The high co-occurrence between ODD and ADHD in childhood . The patients/participants provided their written informed consent to participate in this study.AL was responsible for the design and analyses, interpretation of results, and drafting the manuscript. EN and AH commented on the drafts of the manuscripts. JH contributed as the head of the adult ADHD project and commented on drafts of the manuscript. JM commented on the design, results, and drafts of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder of childhood. Although abnormalities in several brain regions and disturbances of the catecholaminergic pathway have been demonstrated, the pathophysiology of ADHD is not completely understood, but as a multifactorial disorder, has been associated with an increase in oxidative stress and neuroinflammation. This review presents an overview of factors that increase oxidative stress and neuroinflammation. The imbalance between oxidants and antioxidants and also the treatment with medications are two factors that can increase oxidative damage, whereas the comorbidity between ADHD and inflammatory disorders, altered immune response, genetic and environmental associations, and polymorphisms in inflammatory-related genes can increase neuroinflammation. Evidence of an association with these factors has become valuable for research on ADHD. Such evidence opens up new intervention routes for the use of natural products as antioxidants that could have potential as a treatment against oxidative stress and neuroinflammation in ADHD. Diagnostic and Statistical Manual of Mental Disorders (DSM-5), should be carried out when symptoms impair academic, occupational, and social behavior, the onset is before 12 years of age and the symptoms can be observed in multiple settings in the clinical interview, including the gestational, developmental, and family history [Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children characterized by inattention, hyperactivity, and/or impulsivity ,2,3 that history . The wor history ,11,12,13 history ,15.Medications used for ADHD are divided into psychostimulants and non-psychostimulants, which have diverse delivery systems, formulations, and pharmacokinetic actions. Educational and psychosocial approaches are also used as a treatment for ADHD ,16. PsycThe second-line treatment is with non-psychostimulants such as atomoxetine (ATX), which is a selective norepinephrine transporter inhibitor, and selective α-2 adrenergic receptor agonists, namely clonidine and guanfacine ,21,22. NThe heritability of ADHD is high, with a range of 70–80% ,24. GenoThe pathophysiology related to ADHD remains unknown. However, ADHD is associated with abnormalities in the brain due to cognitive and functional deficits. Additionally, links between ADHD and the dopamine levels in specific brain regions have been found: patients with ADHD have attenuated dopaminergic activity ,33. In tOxidative stress is a state produced by an imbalance between antioxidants and oxidants in the cells. The imbalance occurs as a result of the inappropriate function of the antioxidant system or by an excessive level of reactive oxygen species (ROS). Oxidative stress in the brain can harm the integrity of neurons because the brain is rich in polyunsaturated fatty acids (PUFAs) that are highly susceptible to oxidation, producing ROS ,42. ThisMitochondrial dysfunction, genetic, and environmental factors can generate oxidative stress, and inflammation is a neuroprotective response to diverse types of tissue damage. If the tissue is inflamed, it causes an increase of ROS, which can lead to cell death ,47. The Numerous studies have demonstrated elevated levels of oxidative stress in ADHD, increasing the evidence for oxidative stress being a pathophysiological factor. The measurement of higher rates of ethane levels, as a non-invasive measure of oxidative breakdown of n-3 PUFAs in patients with ADHD, was also demonstrated . Furtherl-nitro-arginine methyl ester (l-NAME) [An increase in nitrosative stress  levels) and an impaired balance of oxidants and antioxidants were observed in children with ADHD . In the (l-NAME) . In cont(l-NAME) . On the (l-NAME) ,71. Also(l-NAME) . The outIn a randomized, double-blind, placebo-controlled study, it was found that children with ADHD had decreased total antioxidant status (TAS) . Also, tAs demonstrated in It has been demonstrated that treatment with MPH increases the generation of oxidative stress; in the brain of young rats, chronic treatment with MPH increased oxidative stress as assessed by thiobarbituric acid reactive species (TBARS) and protein carbonyl formation . Also, tThe auto-oxidation of catecholamines (dopamine and norepinephrine) can be easily generated and ROS formed ,90,91; RThe innate and adaptive immune systems work in harmony to support and determine effective and protective immune responses. The innate immune system works as the first line of defense, including the clearance of microbes such as viruses or bacteria, wound repair, and removal of cells that are in the process of dying. Moreover, the innate immune system can later activate the adaptive system. The cells in the central nervous system that participate in the innate immune response are microglia (which are immune cells in the brain), astrocytes, mast cells, natural killer cells, macrophages and oligodendrocytes, circulating phagocytes, and also monocytes, which are the precursors of macrophages and dendritic cells and play a role in innate immunity ,95. The Inflammation of the nervous system, commonly known as neuroinflammation, can be characterized by the activation of microglia , astrocytes, oligodendrocytes, and ependymal cells, by increasing levels of proteases, glutamate, ROS, NO, chemokines, toxic cytokines, and prostaglandins and by infiltration of T and B cells, neutrophils, monocytes/macrophages and dendritic cells ,97,98,99Microglia represents the resident immune cells of the CNS, with an important function in the elimination of waste products during inflammation or damage . The cytAstrocytes have unique functional and morphological characteristics that differ within specific areas of the brain, and brain disorders could be characterized by an inflammatory state of the astrocytes. Thus, astrocytes can drive the induction and progression of the inflammatory state, which is notably related to the disorder condition or severity . SynCAM1An association between cytokines and ADHD symptoms in children has been demonstrated. As a result, elevated levels of IL-16 (hyperactive-impulsive symptoms) and IL-13 (inattention) were found . In patiThe contribution of gene polymorphisms could be associated as a neurodevelopmental risk factor in the pathogenesis of ADHD. Thus, the findings of the IL-1 receptor antagonist (IL-1RA) gene variable number tandem repeat (VNTR) polymorphism in children with ADHD demonstrated that the 2-repeat allele was associated with reduced risk and the 4-repeat allele with increased risk for ADHD . NeverthA possible association between specific antibodies and immune dysregulation in ADHD has been evaluated and a significant positive immunoreactivity against anti-Purkinje cell antibodies in the cerebellum of children with ADHD was found . FurtherA marked comorbidity has been observed between ADHD and asthma , atopic Both maternal obesity and metabolic complications could increase the risk of ADHD in offspring ,121. MorN-Acetylcysteine is a precursor of the antioxidant glutathione, found in the onion and exerts antioxidant and anti-inflammatory activities [Increasing studies are looking for alternative therapies for ADHD, mainly focused on the neuroprotective effects of dietary and natural compounds as antioxidants because they may be alternative treatments with fewer side effects. Some nutritional or natural components which have been studied for having therapeutic benefits in ADHD are: Omega-3 fatty acids have antioxidant and anti-inflammatory activities and the two main are docosahexaenoic acid and eicosapentaenoic acid, found mainly in oily fish ,136,137.tivities . Sulforativities ,136. St.tivities . Passiontivities . Ginkgo tivities ,135,136.tivities ,135,136.The pathophysiological process of ADHD has been associated with an increase in oxidative stress and neuroinflammation. Accordingly, some of the factors discussed in this review appear to play a key role in the pathological process of ADHD. Several factors seem to increase oxidative stress, such as the imbalance between oxidants and antioxidants in patients and also the treatment with medications, both of which could increase the oxidative damage in patients. Moreover, several factors can also cause neuroinflammation in ADHD, such as an altered immune response, genetic and environmental associations, comorbidity between ADHD and inflammatory disorders, and also some polymorphisms in inflammatory-related genes. The aforementioned factors offer the potential for dietary and natural compounds as ADHD therapy, due to the potent antioxidant and anti-inflammatory properties such as the increase of antioxidant levels, reduce oxidative stress, and improve the inflammation. In summary, there are several pieces of evidence for the role of oxidative stress and neuroinflammation in the pathophysiology of ADHD. However, clinical trials and prospective, well-designed studies are still needed to confirm these hypotheses.


Bartonella species are increasingly recognized as agents of culture-negative endocarditis. However, to date, almost all human cases have been associated with two members of the genus, Bartonella henselae and Bartonella quintana. B. henselae infections are zoonotic, with domestic cats serving as reservoir hosts for the pathogen. Bartonella clarridgeiae also exploits cats as reservoir hosts, but its zoonotic potential is far less established.Bartonella species and so the patient was treated post-operatively with ceftriaxone and doxycycline, making a good recovery. Further PCR-based analysis of the patient’s aortic vegetation confirmed the presence of B. clarridgeiae. A 34-year-old male presented with palpitations after a history of aortic incompetence. During surgery for an aortic valve replacement, two vegetations were found on the aortic valve. PCR analysis of the vegetation demonstrated the presence of Bartonella species associated with endocarditis and provides clear evidence that B. clarridgeiae should be considered a zoonotic pathogen. This report expands the number of  Bartonella are characterized as haemotrophic intra-erythrocytic bacterial parasites of a wide range of mammals and several members of the genus are established or emerging zoonotic pathogens. Although cat scratch disease is the most common zoonotic manifestation, a wide spectrum of other syndromes has also been encountered .A specimen of aortic valve was submitted to the Bacterial Identification Section, Antimicrobial Resistance and Healthcare Associated Infections Unit, Public Health England for 16S rRNA gene sequencing, as described previously [escribed , performBartonella infection, the patient received ceftriaxone (2 g daily) and doxycycline (100 mg twice a day) for 6 weeks post-operatively and recovered well.Following the molecular detection of a B. clarridgeiae DNA in human heart valve tissue. We believe that this case represents the first report of human infection by B. clarridgeiae in Ireland and the first report anywhere implicating B. clarridgeiae in aortic root abscess and endocarditis. Furthermore, it is the first time definitive molecular methods have been used to implicate this species in human disease rather than just serology, the specificity of which has been questioned as significant cross-reactions have been observed among Bartonella species and other pathogens [B. henselae or B. quintana antigens, an observation in keeping with one previous B. clarridgeiae case report [Bartonella infections [This report describes the molecular documentation of athogens . Serum fe report  but conte report . This ine report  and/or vfections .Bartonella infection in the literature; B. henselae infection in a patient with a prosthetic aortic valve presenting with nonspecific constitutional symptoms, a skin rash and, subsequently, acute renal failure [Bartonella endocarditis have now been recognized [Bartonella species has been implicated, over 95 % were associated with either B. henselae or B. quintana, with only a handful of cases attributed to other species, Bartonella alsatica and Bartonella vinsonii [B. henselae and B. quintana represent the two most medically important Bartonella species worldwide and it is likely that their relative importance reflects the relatively high rate of human exposure to these species. B. quintana exploits humans as its reservoir host and is transmitted by body lice (Pediculus humanus) infections, and so is frequently associated with disease in those groups of society in which louse infestation is more common, such as homeless people and refugees [B. henselae exploits domestic cats as its reservoir host, a species that has frequent and intimate contact with a significant proportion of the human population [B. clarridgeiae is thought to exploit the same reservoir host, a survey of Irish cats revealed a far lower prevalence of B. clarridgeiae infection (0.8 %) than B. henselae infection (3.4 %), and hence a markedly diminished zoonotic hazard [We can only find evidence of a single case of aortic root abscess associated with  failure . Converscognized ; howeverinsonii . B. henrefugees . B. henpulation . Althougc hazard .B. henselae and B. clarridgeiae, it is likely that the zoonoses they cause share the same risk factors. The age of our patient (34) was close to the mean age of B. henselae endocarditis patients (39) and, like 67 % of these patients, he was male [Bartonella species, human zoonotic infection is likely to be mediated by arthropod vectors, although direct transmission may also occur; the first report of zoonotic B. clarridgeiae infection concerned a veterinarian who developed cat scratch disease following a cat bite [Given the similarities in the ecologies of was male . As withcat bite .Bartonella and other species [Bartonella specific assays performing markedly better than a broad-range bacterial PCR .The increasing use of PCR-based methods on aortic tissue will no doubt increase the detection of infectious endocarditis with  species . However species , with BB. clarridgeiae should be considered in cases of endocarditis and detection of infection may be achieved using PCR and amplicon sequencing on DNA extracted from heart valve tissue.This case report indicates that


Hoarding Disorder (HD) is under recognised and under-treated. Though HD develops by early adulthood, patients present only later in life, resulting in research based largely on samples of predominantly older females. Whilst formerly associated with Obsessive-Compulsive Disorder (OCD), it is now recognised that individuals with HD often have inattention symptoms reminiscent of Attention Deficit/Hyperactivity Disorder (ADHD). Here, we investigated HD in adults with ADHD. Patients in an ADHD clinic (n=88) reported on ADHD, HD and OCD-related symptoms, and compared with age, gender and education matched controls (n=90). Findings were assessed independently in an online UK sample to verify replication using a dimensional approach (n=220). Clinically significant hoarding symptoms were found in ~20% versus 2% of ADHD and control groups, respectively, with those with hoarding being on average in their thirties and with approximately half being male. Greater hoarding severity was noted even in the remaining patients compared with controls (d=0.89). Inattention was the only significant statistical predictor of hoarding severity in patients. Similarly, inattention, alongside depression and anxiety were the greatest predictors of hoarding in the independent sample where 3.2% identified as having clinically significant hoarding. Patients with ADHD had a high frequency of hoarding symptoms, which were specifically linked to inattention. HD should be routinely assessed in individuals with ADHD, as they do not typically disclose associated difficulties, despite these potentially leading to impaired everyday fimctioning. Research in HD should also investigate adults with ADHD, who are younger and with a greater prevalence of males than typical HD samples. Individuals with Hoarding disorder (HD) suffer from excessive clutter, difficulties discarding and often excessive accumulation, causing clinically significant distress or impairment in social and occupational functioning . Historiper se and its treatment is derived from individuals who self-identify. These samples are predominantly female . Patients with ADHD have persistent problems due to inattention and impulsivity, with over half experiencing functional impairments into adulthood . NotablyTo fully understand the association between hoarding and ADHD it is necessary to investigate hoarding in ADHD populations, with ADHD found in 2.5-3.5% of adults . A studyConsideration of the link between hoarding and ADHD exists amongst hoarding specialists, but not amongst adult ADHD clinical and scientific specialists . An invePatients with ADHD were recruited from the NHS Cambridge and Peterborough Foundation Trust Adult ADHD clinic. Diagnoses in clinic were according to DSM-5  and baseControl participants were recruited via advertisements in the local Cambridge community. Screening verified controls did not meet diagnostic threshold for ADHD and included a validated brief ADHD screener  in additThe Adult ADHD Self-Report Scale  assesseThe Savings Inventory Revised  containThe Obsessive Compulsive Inventory-Revised  is wideThe Frost Multidimensional Perfectionism Scale  containDepression and Anxiety Severity Scale  containThe Weiss fimctional Impairment Scale  containEligible and interested participants were sent a link to an online survey, with the data for patients who consented supplemented with in-clinic data . The survey consisted of a demographics section followed by questionnaires presented in random order . All participants provided informed consent before taking part in accordance with the Declaration of Helsinki and were compensated. The study was approved by an NHS Research Ethics Committee (16/WM/0368) and received Health Research Authority approval. The subsequent online study was approved by the University Ethics Panel. Testing procedures for the online sample were identical, with the following exceptions. Four attention check items were included to identify careless responding . Additioand OCIR-Hoarding greater than 6 and a rating of 4 in at least one CIR room. CIR average of 4  and model parameters are reported, with variance inflation factor (VIF) values used to inspect multicolinearity and Cook’s Distance to inspect the influence of individual data points. Values were acceptable, with VIF scores of less than 2.1 for all models.The ADHD and control groups did not differ significantly in gender, age and family status but did in living arrangements see . As expe2(1)=13.64, p<.001). Elevated hoarding in the SIR was also found in patients who were below the threshold compared to controls, . Similarly, these patients had higher OCI-hoarding compared with controls  and higher CIR values .There were 17 patients and 2 controls who scored above the threshold of clinically significant hoarding =0.01, p=.92), with 6 females of the 17 above threshold. There was also no difference in overall medication status with 71% and 82% of those above and below threshold being medicated respectively (χ2(1)=1.04, p=.31). Nor did there seem to be significant patterns in medication type  though a greater proportion above the cut-off were receiving SSRIs . Patients above the threshold reported significantly greater levels of ASRS-inattention  but not ASRS-hyperactivity/impulsivity or BIS impulsivity. This was consistent with their worse inattention symptoms in the BAARS-inattention subscale . Whilst those above the cut-off also had significantly greater BAARS-hyperactivity , this did not survive correction nor were there differences in BAARS- impulsivity or cognitive tempo. Additionally, those above threshold reported greater depression and anxiety , as well as concerns over mistakes  and parental criticism . WFIRS mean functional impairment was higher for the patients above compared to below the threshold .Within the ADHD group, we inspected whether patients with clinically significant hoarding symptoms differed from the remaining patients. We did not observe a significant age difference with all being in their 30’s on average . There was no significant gender difference  whereas BAARS-hyperactivity was significantly associated with SIR-clutter only (rs=0.32) and BAARS-impulsivity was not significantly associated with any SIR subscale. In contrast, in controls both ASRS-inattention and ASRS-hyperactivity were positivity associated with most hoarding indices.Associations between ADHD symptoms and hoarding indices was examined in the ADHD sample . ASRS-in2=0.33) found only inattention to be a significant predictor (2=0.37). Similar regression models including gender and age in both groups or without BlS-impulsivity given concerns over multicollinearity yielded the same results. Additional models indicated similar conclusions for each hoarding subscale when considered separately.In patients, a regression analysis with hoarding  as outcome and ADHD symptom subscales, BlS-impulsivity, anxiety and depression, and OC-related symptoms as predictors (Rredictor . In cont2=0.36). Again inattention was a significant predictor, in addition to depression and anxiety and ordering , with a mean age of 35.78 (SD=12.74). An additional four were removed having failed the attention checks. Clinically significant hoarding symptoms were found in 8 individuals (3.64%). Mean SIR clutter, discarding and acquisition values were 9.68 (SD=5.36), 6.65 (SD=4.64) and 6.61 (SD=4.81), respectively. Mean OCI-hoarding was 3.28 (SD=2.86) and mean CIR was 1.78 (SD=0.73). The association between ADHD and hoarding indices pointed to consistent medium to large associations with hoarding for both inattention and for hyperactivity/impulsivity see . A regreordering .The findings show significantly elevated hoarding symptoms in adult individuals with ADHD compared to controls matched for key demographic characteristics. Clinically significant levels of hoarding were reported by approximately 20% of ADHD patients, similar to levels previously reported in OCD cohorts . PatientConsideration of comorbid hoarding in ADHD should contribute to behavioral and pharmacotherapy treatment choices. For example, preliminary open-label data suggest atomoxetine may be effective for HD symptoms , as do sPresent findings point to a robust and unique association between hoarding and inattention extending previous OCD and HD studies to patients with ADHD . IndividDespite some overlap, inattention and impulsivity/hyperactivity are separate domains with domain specific genetic influences . A uniquCurrent findings also highlight the presence of patients with hoarding who were on average in their thirties. There was no gender difference in the ADHD sample, nor was gender associated with hoarding severity in the other samples. Patients above the hoarding cut-off were closer in demographic profile to that expected in the population compared to typical research studies . This imThe present study did not assess the phenomenology of hoarding, such as the presence of a strong emotional and sentimental attachment to possessions . This coThe present study relied on self-report rather than clinician-rated measures of hoarding with the study information mentioning ‘accumulation behaviors’, allowing potential biasing in the ADHD participants. However, the control group was provided with identical information and experienced the same procedures mitigating this concern, as did the replication in the online sample of the link with inattention. Additionally, multiple well-validated measures for ADHD and HD-related symptoms were collected, while employing previously established cut-off values for HD. This allowed us to avoid an overly liberal approach to hoarding difficulties. Moreover, present criteria yielded an online sample prevalence within the confidence intervals of a recent meta-analyses .In sum, this study points to a hidden population of adults who demonstrate clinically significant hoarding symptoms. Inattention symptoms were specifically linked to hoarding severity and this was replicated in an independent online sample. The results suggest hoarding symptoms should be assessed in patients with ADHD, particularly given insight issues. Moreover, HD research should actively investigate hoarding in such individuals given their age and gender ratio. A better understanding of the overlap between HD and ADHD will enrich theorizing and treatment development to ultimately improve functioning and outcomes for all.


Patient body size represents the main determinant of parenchymal enhancement and by adjusting the contrast media (CM) dose to patient weight may be a more appropriate approach to avoid a patient over dosage of CM. To compare the performance of fixed-dose and lean body weight (LBW)-adapted contrast media dosing protocols, in terms of image quality and parenchymal enhancement.n = 50) received 120 mL of CM while in LBW group (n = 50) the amount of CM was computed according to the patient’s LBW. LBW protocol group received a significantly lower amount of CM . Arterial kidney signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) and pancreatic CNR were significantly higher in LBW group . LBW group provided significantly higher arterial liver, kidney, and pancreatic contrast enhancement index (CEI) and portal venous phase kidney CEI . Significantly lower portal vein SNR and CNR were observed in LBW-Group .One-hundred cancer patients undergoing multiphasic abdominal CT were prospectively enrolled in this multicentric study and randomly divided in two groups: patients in fixed-dose group (LBW-adapted CM administration for abdominal CT reduces the volume of injected CM and improves both image quality and parenchymal enhancement. Lean body weight (LBW) group received significantly lower amount of contrast media.Higher arterial contrast enhancement index (CEI) and kidney portal-venous CEI in LBW-group.LBW protocol may be considered for routine to improve CT performance.Contrast-enhanced CT is the imaging modality of choice for the study of the abdomen in a large spectrum of diseases. Patient body size is known to be a major determinant of parenchymal enhancement, and it has been shown that adjusting the contrast media (CM) dose to patient weight may be a more appropriate approach than administering a fixed dose of CM, allowing to reduce inter-patient variability and unnecessary healthcare costs related to CM over dosage –6. HowevDue this lack of standardization, multiple weight-adapted CM dosing regimens have been proposed, based on a large variety of body size indexes, including total body weight (TBW), body mass index (BMI), lean body weight (LBW), and body surface area (BSA), but no consensus on has been reached so far –13.Dosing CM according to patient TBW does not require complicated calculations and, given its quickness and ease of use, can be readily implemented in the daily routine; nonetheless, it fails to take into account differences in body composition. In particular, TBW-adapted regimens may lead to an overestimation of CM volume in overweight and obese patients, in which scarcely perfused adipose tissue contributes for a considerable proportion of body weight , 15. DifPromising results have been reported by previous studies investigating CM dosing protocols based on LBW rather than TBW, which resulted in a reduced inter-patient variability of parenchymal and vascular enhancement , 18. TaiTherefore, our aim was to perform a prospective multicenter study to compare the performance of fixed-dose and LBW-adapted CM dosing protocols for multiphasic abdominal CT, in terms of image quality and parenchymal enhancement.2); (d) pregnancy; (e) deviation from injection and acquisition protocol and (f) presence of image artifacts deemed to impair quantitative measurement. Data on patient age, gender, height, primary cancer, TBW, LBW and BMI were recorded for all participants.This prospective randomized multicenter study was conducted at two centers  and was approved by the Institutional Review Board of both participating institutions. Written informed consent was obtained from all patients and the study was compliant with the Health Insurance Portability and Accountability Act. From November 2018 to March 2019 oncologic patients clinically referred for multiphasic contrast-enhanced abdominal CT were prospectively enrolled. Exclusion criteria were as follows: (a) age < 18 years; (b) history of allergic reactions to iodinated CM; (c) kidney failure , was intravenously injected at a fixed flow rate of 3.0 mL/s (Iodine delivery rate of 1.05 gI/s) through an 18-gauge antecubital access by using an automated dual-syringe power injector  and followed by a 50 mL saline chaser administered at the same flow rate.W is the patient weight in kilograms and H is the patient height in meters. For each CT examination, the volume of administered CM was recorded.Patients were randomly assigned into one of two CM dosing protocols using a randomization list on a 1:1 basis. Patients in the fixed dose protocol group received a fixed CM dose of 120 mL [42 g of iodine (gI) ]. Patients in the LBW protocol group received 0.7 gI per kg of LBW . The res follows :\documenImaging was performed by using a 64-row multidetector CT scanner  or with a 256-slice CT , based on the reference centre. However, both in fixed dose protocol group and in the LBW protocol group the number of CT scans performed with two different CT scanners were equivalent, as reported in Table z-axis tube current modulation  was applied with a noise index of 28 (min/max tube current: 200/600 mAs).Scanning parameters for 64-row CT have been set as follows: tube voltage, 120 kVp; beam pitch, 1.375:1; detector configuration, 64 × 0.625 mm. A For 256-slice CT, scanning parameters were: tube voltage, 120 kVp; beam pitch, 1; detector configuration, 2 × 128 rows × 0.625 mm; tube load from 200 to 600 mAs depending on automatic mA current modulation , with a Dose Right Index (DRI) of 22 and a Liver DRI of + 2.All examinations were performed with patient in supine position and in a cranio-caudal direction, from the diaphragmatic dome to the pubic symphysis. The scan delay was determined using a bolus-tracking software program , with the placement of a 100 HU-threshold region-of-interest (ROI) within the abdominal aorta at the level of the celiac tripod. All patients in the two centres underwent a hepatic dynamic scan, including a pre-enhanced phase, a late arterial phase acquired 16 s after reaching the threshold, and a portal venous phase acquired 70 s after reaching the threshold.Image datasets were reconstructed at the CT scanner console with the following parameters: slice thickness of 1.25 mm and spacing of 1.25 mm. Iterative reconstruction programs, “ASiR 40%; GE Healthcare” and “iDose4—level 2; Philips Healthcare”, were applied, as vendors suggested.2 in the liver , renal cortex of both kidneys, pancreas, and left psoas muscle in both arterial and portal venous phase. Supplementary ROIs were placed in the suprarenal abdominal aorta on arterial phase images and in the portal vein on portal venous phase images. All measurements were performed three times at the same levels and then averaged to ensure consistency. The mean of the 3 averaged liver ROIs was obtained to define the liver HU; kidney HU was defined as the mean of right and left kidney averaged ROIs. Image noise was defined as the SD measured in a circular ROI placed in subcutaneous fat tissue.In both centres, a reader with at least 3 years of experience (DDS) in abdominal radiology analysed all images. Attenuation measurements in HU and standard deviation (SD) values, were obtained in axial scans, by positioning a circular ROI of approximately 1 cmArterial liver, pancreatic, kidney and aortic signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as portal venous phase liver, pancreatic, kidney, and portal vein SNR and CNR were calculated as follows :\documenLiver, kidney and pancreas contrast enhancement on both arterial and portal venous phase was quantified by calculating the contrast enhancement index (CEI) as follows :\documenSubjective image quality was assessed independently by two experienced abdominal radiologists (M.Z. and N.P.) at each centre. All readers were unaware of which CM dosing protocol had been used. Image datasets were primarily displayed with standard window settings for evaluation of soft tissue . However, readers were allowed to freely adjust window width and level values according to their preferences. The enhancement of the liver, kidneys, and pancreas was rated by using a 5-point Likert scale as follows: 1 = very poor; 2 = poor; 3 = fair; 4 = good; 5 = excellent .http://www.medcalc.org; 2017). Continuous variables were expressed as mean ± SD or mean with ranges. Ordinal variables were expressed as median with ranges. Patient characteristics , SNR, CNR, and CEI, were compared between the two groups. The Kolmogorov–Smirnov test was used to assess data distribution. For normally distributed data, Student’s t test was applied. In case of non-normally distributed data, Mann–Whitney U test was performed. The x2 test was used to calculate differences in gender and type of primary cancer between the two study groups.Statistical analysis was performed by using the MedCalc5 Statistical Software version 17.9.7 , kidney failure (n = 3), deviation from injection protocol (n = 2) and the presence of artifacts (n = 3). Therefore, 100 patients were finally enrolled in the study population: 50 patients in the fixed dose protocol group and 50 patients in the LBW protocol group. No significant differences were observed between the two groups in terms of patient age, gender, BMI, and LBW . Detailed patient characteristics are reported in Table One-hundred-ten consecutive patients were prospectively included in the study, 10 individuals were excluded due to previous allergic reactions to iodinated CM n = , kidney p < 0.001) and corresponding volume , as shown in Table The administered CM dose was significantly lower in LBW protocol group compared to fixed dose protocol group, both in terms of gI , pancreatic arterial CNR , pancreatic arterial CEI , kidney arterial SNR , and kidney arterial CNR . Kidney CEI was superior in LBW protocol group in comparison with fixed dose group for both arterial  and portal venous phase .LBW protocol group accounted for significantly higher liver arterial CEI  and CNR  were observed in LBW protocol group compared to fixed dose group.Significantly lower portal vein SNR . Results of objective image quality analysis are summarized in Table No significant differences were observed in any of the remaining image quality parameters evaluated on both arterial and portal venous phases . No patients scored very poor or poor enhancement in both groups.Detailed results are reported in Table κ = 0.81 (95% CI 0.76–0.87)) and LBW protocol (κ = 0.87 (95% CI 0.81–0.93)) groups.Overall inter-rater agreement was excellent for both fixed dose protocol , additional studies would be required to demonstrate the reproducibility of our result when using CM with different iodine concentrations. Second, we solely evaluated the performance of LBW-adapted protocol in terms of image quality, further analysis to determine also the effects on lesions’ conspicuity and diagnostic accuracy was not investigated. Third, we calculated the LBW of each patient by using James formula; however, several prediction formulas for LBW have been previously reported and their application may yield results different from those observed in our study , 28. HowIn conclusion, the results of this prospective randomized multicenter study demonstrate that dosing CM according to patient’s LBW rather than administering a fixed dose of CM allows for a significant reduction of the injected CM volume with no detrimental effects on image quality and parenchymal enhancement. Implementation of an LBW-adapted protocol should be considered in oncologic patients in order to reduce costs and minimize the risks of contrast-induced acute kidney adverse events.


The aim of this study was to analyse whether the global trend in drug prescriptions for attention-deficit hyperactivity disorders (ADHD), as observed during the last years and often criticized as medicalization, have remained stable or shifted.This observational study was based on a secondary analysis of data from a large German database including patients with an ADHD diagnosis between 2008 and 2018. Prescription data comprised all important ADHD drugs.A total of 620 practices delivered data from a total of 77,504 patients  with a diagnosis of AHDH. Nearly 38%  of all patients received, at least, one prescription for an ADHS medicine between 2008 and 2018. The number of patients receiving a drug steadily increased annually until 2012 and then slowly fell, but unevenly distributed across the age groups. While the number of younger patients ( ≤ 16 years) receiving a prescription fell by 24% and the defined daily doses (DDDs) remained stable, the number of patients between 17 and 24 years receiving a prescription increased by 113% and the DDDs by 150%. Respectively, the number of older adults (≥ 25 years) with a prescription increased by 355% and the DDDs by 515%. Nearly one-third of older adults received an ADHD medicine only once.The ever-increasing prescription of ADHD medicines stopped some years ago for children. ADHS and its pharmacological management are increasingly observed among older adolescents and adults, with a different pattern of drug persistence compared with children.The online version of this article (10.1007/s00228-020-02948-3) contains supplementary material, which is available to authorized users. Attention-deficit/hyperactivity disorder (ADHD) is among the most common neurobehavioural problem afflicting children and adolescents. Individuals suffering from this disorder exhibit hyperactivity, inattention, impulsivity and problems in social interaction and academic performance . In a suThe number of prescriptions and the number of children who take ADHD drugs have increased dramatically in various European countries , and recThere are several concerns about the pharmacological management of ADHD. Methylphenidate, the most commonly prescribed medicine, is associated with an increased risk of non-serious adverse events, such as sleep problems and decreased appetite . MoreoveDespite these concerns, new guidelines on the management of ADHD recommend a more liberal use of these drugs. For example, the guideline of the National Institute for Health and Care Excellence (NICE) recommends pharmacotherapy as first-line treatment for adults , althougAdditionally, and in remarkable contrast to these concerns, we witness a constantly repeated warning of an allegedly insufficient awareness of “adult ADHD”  and its In other words, we face a mixture of fears of overtreatment of children/adolescents and undertreatment of adults. In this situation, new and valid data that highlight the prescription of these drugs are key for optimal treatment and rational discourse. According to Beau-Lejdstrom and Magno Zito , it is eThis observational study was based on a secondary analysis of data from a large database provided by IMS/IQVIA . For datThe IMS® Disease Analyzer contains anonymized data obtained from the practice computers from office-based physicians specializing in various disciplines. The database records, in addition to other data, ICD-10-coded diagnoses, prescriptions, referrals and dates of appointments. The database contains data from 2498 practices  and appeThe authors obtained data from a part of the database that included all patients with at least one diagnosis of ADHD (ICD-10-CM: F90 attention-deficit hyperactivity disorders) between 2008 and 2018, including information on physician specialty, patient’s age and sex, diagnosis expressed as ICD 10 codes (up to level 4), date of diagnosis and referrals. Prescription data comprised date of visit, product expressed as an anatomical therapeutic chemical (ATC) code, strength and pack size.All data are physician-related and patient-related only for a single practice so that a patient could not be followed if he or she changed practice.Analysis included drugs approved for treatment of ADHD in Germany: dexamfetamine, lisdexamfetamine and methylphenidate as stimulants and atomoxetine and guanfacine as non-stimulant drugs.Defined daily doses (DDDs) were calculated from the prescribed strength and pack size for each prescription. For persistence, according to the date of the first prescription, we calculated the months between the first and last prescription until there were no further prescriptions within 360 days.For some analyses, we divided the patients into 3 age groups as follows: children, adolescents (16 years and younger), young persons (from 17 years to 24 years) and adults (25 years and older), similar to a classification in a French observational cohort study that assessed patterns of methylphenidate use in children and adults . We deliIn most instances, the unit of analysis was the ADHD diagnosed patient with a prescribed ADHD medication. Only descriptive statistics, such as absolute and relative frequencies, as well as the means, medians and interquartile ratios (IQRs), were calculated. For a sensitivity analysis, we changed the stop criterion for persistence from 360 days to a gap of up to 180 days.A total of 620 practices, including 437 primary care physicians, 92 paediatricians, 64 neurologists and 27 psychiatrists, delivered data from a total of 77,504 patients with a diagnosis of ADHD. The patients were, on average, 18.9 (median: 12) years old at the time of the first diagnosis of ADHD and/or the first ADHD prescription; 30.8% of them were female.Nearly 38%  of all patients received at least one prescription for an ADHD medicine during the time period under study; 26%  of them were female.The number of patients receiving a drug steadily increased annually from 6613 in 2008 to 8969 in 2012 and then fell to 7533 in 2018  is still by far the most prescribed medicine for ADHD, followed by lisdexamfetamine, which was first prescribed in 2013, and atomoxetine. The three substances differ in regard to the targeted population. Methylphenidate was the dominant substance 10 years ago, with more than 90% of patients receiving this drug. This number decreased for children/adolescents from 92% to 81% of the patients  and from 98% to 91% for adults (from 99% to 91% DDDs). Lisdexamfetamine increased, especially in children/adolescents . The share of atomoxetine grew, but not steadily, in adults and decreased in children/adolescents.When we considered the patient’s age at therapy initiation, we observed some age differences Fig. . During n = 29,396). These patients received their prescriptions of an ADHD medicine for 22 months, on average . The results differed substantially according to the age of the patients. While especially the patients younger than 12 years remained under treatment, on average, for 2 years or longer, adult patients received medication for a much shorter time  of all patients had at least one other diagnosis from Chapter 5 ICD-10-CM . This figure was somewhat higher in children/adolescents (76%) than in those aged 17 to 24 years (60%) or ≥ 25 years (63%). More importantly, the single diagnoses differed markedly between the age groups  diagnosis and no other diagnosis from ICD-Chapter 5 ICD-10-CM received a drug, it was 37.6% of those with at least one additional F-diagnosis  use ADHD medicines, on average, for a much shorter period of time than children and adolescents. Psychiatric comorbidities were frequent among persons with an ADHD diagnosis but did not seem to be decisive for a drug prescription.We had access to a large and continuous data set from community practices, covering general practices as well as paediatric, neurological and psychiatric practices in Germany. The data comprised the last 10 years, with diagnoses and drug prescriptions as well as the age and sex for persons with an ADHD diagnosis. The sample of practices was deemed to be representative of German practices  and was A limitation of the data source is that it only documents prescribed medications but not whether they are really dispensed from a pharmacy. However, comparing our main results with global prescription data from German health insurance companies, our study approach seemed to yield valid results. Lohse and Müller-Oerlinghausen , 25, forWe could follow up the participants using a pseudonymized code but only within one practice and not across several practices. We probably underestimated, to a certain degree, drug supply and persistence of those who received their prescriptions from more than one practice or changed the practice during the time period under study. Patients, however, do not change practice frequently in Germany, with more than 85% of the patients visiting only the same, or maximum two general practitioners (GPs) and more than 90% visiting only the same or a maximum of 2 paediatricians, neurologists or psychiatrists . HoweverThe frequency and quantity of prescriptions of methylphenidate are still a major concern in the scientific and public communities (not only) in Germany . PortionThe cessation or slight decrease in methylphenidate use in recent years seen in our study was also observed in another German pharmacoepidemiological study . AccordiMoreover, and in remarkable contrast to these concerns, we witnessed a constantly repeated warning of an allegedly insufficient awareness of “adult ADHD”, including an ongoing debate whether a significant proportion of adults remain undiagnosed and, consequently, untreated , 17–19. First, many studies have documented an increase in adults diagnosed with ADHD who are receiving respective medicines worldwide, with relative increases in medication use per year of 17 to 19% for adults until 2015, compared with only 9 to 15% for non-adults . Two US Second, based on an estimated transition rate from childhood to adult ADHD of approximately 50% , severalThird, recent research  suggestsThe obvious sensitivity towards such ADHD symptoms together with therapeutic attempts also contradicts the hypothesis that doctors neglect adult ADHD. Although some adults may still be undertreated or do not receive medicines at all, the lack of persistence observed in our study may be, at least partly, explained by “overtreatment” of those adults who were treated empirically with ADHD medicines for symptoms similar to ADHD symptoms but stopped the treatment probably because they did not experience a benefit. Different patterns of methylphenidate use among adults were also observed in Pauly et al.’s study where drug persistence decreased with age and adults who used methylphenidate had more psychiatric disorders than the younger ones .The ever-increasing prescription of ADHD medicines, a major concern of the public and many researchers, stopped some years ago and even decreased in some age groups. While new guidelines obviously did not lead to an increasing trend in methylphenidate use among children, we should not overrate the decline in the use of these medicines. The reduction was very small, so the use of methylphenidate is still high.However, there are still not enough data about the benefits and risks of long-term therapy, and post-marketing surveillance studies in community populations may be helpful. Even so, a stronger focus on the role of comedication—particularly interacting comedication or medication classes like atypical antipsychotics possibly prescribed for ADHD—may be helpful to better understand the decision to prescribe or not to prescribe an ADHD medicine and drug persistence.What is surprising is the call to give adults and their pharmacological supply more attention. Considering the strong rise in drug supply of adults and the notable prescriptions pattern for this patient group, our analysis shows that doctors pay greater attention towards adults with a possible diagnosis of ADHD and a possible undertreatment of them.Our pharmacoepidemiological analysis does not allow for inferences about the adequacy of the drug trends or the benefits of the medicines prescribed. At best, this analysis deepens our knowledge about recent trends and indicates risks and blind spots  in the sESM 1(DOCX 14.6 kb).ESM 2(DOCX 16.5 kb).


There is a growing trend of using energy drinks and caffeinated beverages to improve cognitive performance that is widespread and well-studied among children and teenagers with Attention Deficit Hyperactive Disorder (ADHD), but little is known about adult ADHD (A-ADHD). As a consequence, the use of highly caffeinated drinks and their impact on ADHD symptoms are poorly understood. This is especially true in populations where A-ADHD and the use of these beverages are largely represented, such as in military samples. From the All Army Study (AAS) of the Army Study to Assess Risk and Resilience in Service members (STARRS) data, 1,239 A-ADHD soldiers and 17,674 peers without any psychiatric comorbidity were selected. The two groups were compared on: (1) the presence of substance use disorder (SUD) diagnosis both over their lifetime and in the previous 30 days; (2) patterns of alcohol and caffeine use using chi-square analyses. Lastly, the relationship between substance use and severity of A-ADHD symptoms was assessed using Pearson’s correlations. Soldiers with a diagnosis of A-ADHD had a higher prevalence of SUD diagnosis compared to their peers without psychiatric comorbidity. They also tended to use more alcohol, caffeine pills, energy drinks, and other caffeinated drinks. Alcohol use was positively correlated with A-ADHD symptoms; on the contrary, energy drinks, caffeine pills and other caffeinated drinks showed negative correlations with some aspects of A-ADHD symptomatology. The use of caffeinated compounds appears to be increased among military soldiers with ADHD, and they may help reducing A-ADHD symptoms and improve cognitive performance. These results suggest a possible role for caffeine as a potential pharmacological tool in the treatment of adult ADHD. Attention Deficit/Hyperactivity Disorder (ADHD) is characterized by excessive inattention and/or hyperactivity and impulsivity, as well as executive dysfunction, a broad spectrum of emotional dysregulation with scarce self-control, lack of motivation and functional impairment. In terms of epidemiology, ADHD is estimated to affect 3% to 9% of school-aged children and approximately 4% of adults worldwide ,2,3,4,5.Although ADHD is often thought of as a childhood disorder, it often continues beyond adolescence, as shown in long-term controlled follow-up studies. In fact, the disorder seems to persist in a considerable number of adults previously diagnosed with ADHD in childhood . A relevNevertheless, the discipline of a highly structured training context as in military ones might represent a fertile environment for developing organizational skills for A-ADHD soldiers. Moreover, physical training and exercise might reduce at least some of their symptomatology, as shown in a comparative study of soldiers with and without a history of ADHD in all-volunteer military setting in the USA. Rates of retention, promotion, and mental health-related outcomes during a 5-year period, in fact, showed efficient levels of functioning in those subjects . HoweverSubstance use disorder (SUD) is among the most common comorbid psychiatric conditions in A-ADHD. Substance abuse or dependency is approximately twice as common in individuals with A-ADHD compared to the general population, as a diagnosis of ADHD in childhood leads to a higher vulnerability to substance use and abuse, with an increased risk of developing SUDs among individuals in their 20s and 30s. This reciprocal interaction probably originates from various sources including neurobiological factors and shared genetic risk factors, other comorbid psychiatric disorders, behavioural and temperamental characteristics such as novelty-seeking or impulsivity. In particular, the main drugs of use in the A-ADHD population are alcohol,  nicotineLittle is known about the role of “licit” drugs, such as energy drinks and other caffeinated compounds and their impact on A-ADHD symptomatology and severity. The lack of findings is striking given that worldwide consumption of these products has steadily increased in the past two decades, and they are advertised for their claimed properties of increasing energy and athletic performance and supporting weight loss . These bIn contrast, the positive influence of caffeine and derivates on working memory, alertness and, in general, cognitive performance is well-established, with some authors recommending low  doses ofto explore the use of caffeine, caffeinated drinks and alcohol among soldiers with A-ADHD in order to cope with the cognitive impairment of their condition in the light of the SMH;to investigate the impact of these compounds on ADHD clinical features and symptom severity.The aims of the present study were:The analyses were conducted using data from the All Army Study (AAS) of the Army Study to Assess Risk and Resilience in Service members (STARRS) database, comprising 674,335 United States (US) Army soldiers recruited in quarterly samples from active duty Army personnel.The AAS study was designed to assess factors related to suicidal risk in military personnel, since suicide rates in the US military has become the second main cause of death behind combat deaths, after the beginning of the Iraq and Afghanistan conflicts, exceeding demographically-matched civilian rates since 2008 ,26,27.From the All Army Study (AAS) of the Army Study to Assess Risk and Resilience in Service members (STARRS) database we focused on the military personnel deployed in Operation Iraqi Freedom/Operation Enduring Freedom  for matching demographics and for the sake of stressor exposure as all models were adjusted for person-year, sex and race-ethnicity. Of these subjects, we selected 1239 soldiers with A-ADHD and 17,674 peers without evidence of psychiatric disorders taken from the original sample, i.e., scoring negatively for all the psychiatric diseases assessed by the questionnaire. Moreover, the population of A-ADHD subjects was diagnosed in childhood, therefore previous to deployment.The AAS is a self-administered questionnaire that was completed between 2011 and 2013, at relatively random times other than at the very beginning or very end of deployment firstly in 2010–2011 in Iraq, and secondly, in 2012–2013, to a supplemental sample unit of soldiers in Afghanistan.The survey examines current  and lifetime presence of eight internalizing disorders: major depressive episode (MDE), posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), agoraphobia (AGO), specific phobia (SP), social phobia (SO), and obsessive-compulsive disorder (OCD), attention deficit and hyperactivity disorder (ADHD); as well as one externalizing disorder: substance abuse or dependence (SUB/D). Diagnoses were established without DSM-IV diagnostic hierarchy or organic exclusion rules .To assess A-ADHD symptomatology, the survey used the Adult ADHD Self-Report Scale Screener (ASRS-S) . The fulThe Composite International Diagnostic Interview (CIDI) screening scales for mental health disorders were used to determine the number of current and lifetime mental health disorders. The CIDI Substance Abuse Module, in particular (CIDI-SAM) assesses tobacco, alcohol, drug and caffeine usage in the past 30 days. This measure was developed for clinical and research use, including epidemiological studies; it has demonstrated adequate validity and reliability .The use of over-the-counter stimulant substances was assessed, including use of energy drinks , other caffeinated drink ; caffeinated gum and caffeine or energy pills . Each of the items were investigated in terms of frequency of use on the following scale: every or nearly every day, 3–4 days a week, 1–2 days a week, less than 1 day a week or never, using the past 30 days as the time frame. In addition, the quantity of daily consumption of cigarettes, caffeinated products and energy and alcoholic drinks was assessed. Quantity of daily use was dichotomized as low (less than three per day) or high (3 or more per-day), corresponding to the intake of up to 400 mg/day of caffeine as recommended by the recently released Dietary Guidelines, Health Canada and the European Food Safety Authority.For alcohol, the Dietary Guidelines for Americans defines moderate drinking as up to 1 drink per day for women and two drinks for men .Since our sample was mainly represented by male individuals, we chose to apply the two-drink a day limit to all our samples .Furthermore, alcohol use was divided into “any drinking”  and “heavy drinking”  for each week in the past 30 days.Finally, none of the data in the analyses included caffeinated alcoholic beverages.p < 0.05, without operating any correction for multiple comparisons.These analyses focused on AAS participants who met criteria for current A-ADHD who were compared to soldiers without evidence of any psychiatric conditions. Chi-square tests were used to compare these groups on: the presence of SUD diagnosis over the lifetime and in the previous 30 days; alcohol and caffeine use. Lastly correlations between use of substances and severity of A-ADHD symptoms were assessed according to the Spearman correlations. SAS system software (version 9.4) was used for our analyses. In consideration of the exploratory nature of the study, we referred to levels of significance of Demographic data are reported in In this sample of US Army soldiers, individuals with A-ADHD displayed a higher proneness to suffer from SUD, scoring higher in every domain of the substance use section of the survey, compared to the those without current a psychiatric diagnosis, as a self-relief tool to alleviate ADHD distress, again supporting the SMH.As previously mentioned, both children and teenagers with ADHD likely develop an increased tendency towards Energy, Caffeine and Caffeinated drink (ECC) consumption and caffeine misuse, with higher rates of intoxication and dependence compared to their peers .In line with these findings, the same trend seems to remain also in adulthood, as our data might confirm, consistently and with the general higher tendency of patients with ADHD to develop SUD, regardless of the drug involved.Thus, the goal of this study was to evaluate the hypothesis of a higher tendency towards use of stimulant compounds in adults with ADHD. The findings are consistent with this hypothesis, since soldiers with ADHD consumed more caffeinated beverages compared to their non-ADHD colleagues on a weekly basis.Significantly, in the military population a high rate of energy drink intake is common, and caffeine has been proved to improve reaction time, vigilance and logical reasoning during extended periods with restricted opportunities for sleep, to help sustain workplace safety and productivity . Since mHowever, it is important to note that R squared values were very small, thereby affecting the strength of these correlations, which did not involve most of ADHD clinical features, but only some of them, as reported.Besides this, the relationship between ADHD symptom severity and use of caffeine seems to point towards a lower impairment of ADHD symptoms in ECC users, defining an inverse correlation among stimulating compounds (caffeine) and ADHD symptom severity which is not replicated when alcohol use is assessed. In fact, alcohol use seems to worsen clinical features except for fast driving where no differences are detected between caffeine use and alcohol users, as both positively affect ADHD driving capacity with a lesser tendency towards dangerous driving. In particular, a possible explanation for the association between A-ADHD and alcohol use that emerges from our analysis could be found in the search for a “relief from relief” effect, where the excessive noradrenergic activation derived from the intake of caffeinated compounds to improve the impaired cognition is compensated with alcohol due to its sedative and hypnotic properties. Therefore, they may try to counterpoise the caffeine-triggered worsening of insomnia and anxiety with alcohol intake, again following the self-medication hypothesis.For years, the role of caffeine and, more recently, caffeinated drinks has been strongly debated, in consideration of the risk of developing impulsive behaviours up to aggression, irritability and dysphoric mood, increased heart rate, high blood pressure and seizures, together with possible intoxication and withdrawal, especially during the developmental age.In contrast, the positive influence of caffeine and derivatives on working memory, alertness and, in general, cognitive performance has always been undeniable, with some authors suggesting low doses of caffeine in ADHD children, together with prescribed stimulants as a complementary compound, amplifying their therapeutic effects . ComparaThese soldiers with A-ADHD, in fact, although not being completely representative of A-ADHD in the general population, might be considered as high-functioning, with the disease at a low degree in terms of symptom severity and social impairment. In recent work, Nock and colleagues  analysedThe major limitation of this study is its absence of information regarding possible current specific treatments for A-ADHD. Regarding the presence of psychiatric comorbidity in A-ADHD soldiers, we decided not to adjust for their existence, because the majority of analyses conducted were Chi-square tests, which do not allow the inclusion of covariates for adjustment. Besides, the control sample was without psychiatric comorbidities, and caffeine tends not to have a positive effect on mood and anxiety disorders.The AAS source data were collected among military personnel and thus, it may not be perfectly representative of the general population. The survey was designed before the release of DSM-5 and, consequently, the diagnostic criteria in it still refers to the previous edition of the manual, DSM-IVR. Furthermore, this is a retrospective analysis; we cannot infer incidence rates of the diseases we focused on. At the time of filling out the questionnaire, some soldiers had already been deployed; others were still waiting for a call to combat. Therefore, some heterogeneity in our sample cannot be excluded.Finally, the effects on ADHD symptoms are subjective; therefore, neuropsychological studies are recommended to confirm our results.Given the lack of data regarding A-ADHD and the use of ECC, we investigated the role of caffeine and caffeinated compounds on cognition and impulsive behaviour, finding a positive influence of caffeine at variable degrees. Therefore, our data may suggest the use of caffeine as an adjuvant and a promising treatment tool to implement the efficacy of currently prescribed stimulants.However, more efforts have yet to be made in this field of research to identify the correct therapeutic dosage of caffeine and to lessen the impact of side effects, perhaps by discovering new molecules such as adenosine receptor antagonists.