Epilepsy severity mediates association between mutation type and ADHD symptoms in tuberous sclerosis complex.

The association between attention-deficit/hyperactivity disorder (ADHD) and tuberous sclerosis complex (TSC) is widely reported, with support for the role of epilepsy, yet the mechanisms underlying the association across development are unclear. The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of TSC. In Phase 1 of the study, baseline measures of epilepsy, cortical tuber load, and mutation were obtained with 125 children ages 0-16 years. In Phase 2, at an average of 8 years later, ADHD symptoms were measured for 81 of the participants. Structural equation modeling revealed an indirect pathway from genetic mutation, to cortical tuber load, to epileptic spasm severity in infancy, to ADHD symptoms in middle childhood and adolescence, in addition to a pathway linking current seizure severity to ADHD symptoms. Findings were retained when intelligence quotient (IQ) was entered as a correlated factor. The findings support a cascading developmental pathway to ADHD symptoms mediated by early-onset and severe epilepsy in the first 2 years of life. This warrants detailed investigation of seizure characteristics and cognitive and behavioral sequelae associated with ADHD from early in life, to further the understanding of the association between ADHD and early-onset epilepsy across syndromic and non-syndromic populations.

Silicon membranes for extracorporeal life support: a comparison of design and fabrication methodologies.

Extracorporeal life support is an advanced therapy that circulates blood through an extracorporeal oxygenator, performing gas exchange outside the body. However, its use is limited by severe complications, including bleeding, clotting, and hemolysis. Semiconductor silicon-based membranes have emerged as an alternative to traditional hollow-fiber semipermeable membranes. These membranes offer excellent gas exchange efficiency and the potential to increase hemocompatibility by improving flow dynamics. In this work, we evaluate two next-generation silicon membrane designs, which are intended to be mechanically robust and efficient in gas exchange, while simultaneously reducing fabrication complexity. The "window" design features 10 µm pores on one side and large windows on the back side. The "cavern" design also uses 10 µm pores but contains a network of interconnected buried caverns to distribute the sweep gas from smaller inlet holes. Both designs were shown to be technically viable and able to be reproducibly fabricated. In addition, they both were mechanically robust and withstood 30 psi of transmembrane pressure without breakage or bubbling. At low sweep gas pressures, gas transfer efficiency was similar, with the partial pressure of oxygen in water increasing by 10.7 ± 2.3 mmHg (mean ± standard deviation) and 13.6 ± 1.9 mmHg for the window and cavern membranes, respectively. Gas transfer efficiency was also similar at higher pressures. At 10 psi, oxygen tension increased by 16.8 ± 5.7 mmHg (window) and 18.9 ± 1.3 mmHg (cavern). We conclude that silicon membranes featuring a 10 µm pore size can simplify the fabrication process and improve mechanical robustness while maintaining excellent efficiency.

Correlation between the total number of features of paediatric pseudotumour cerebri syndrome and cerebrospinal fluid pressure.

PURPOSE: Accurate diagnosis of pseudotumour cerebri syndrome (PTCS) in children is challenging. We aimed to see if the clinical and radiological assessment that is carried out before lumbar puncture could predict subsequently recorded CSF pressures, and thus whether it could be used to increase diagnostic certainty of paediatric PTCS. METHODS: We used internationally recognised diagnostic criteria to derive a list of clinical, brain neuroimaging and venography features that were accepted to be associated with a diagnosis of PTCS. We performed a retrospective cohort study of children referred to our centre with suspected PTCS, identifying the presence or absence of those features for each child at initial presentation. The sum total scores of the features that were present were correlated with the child's recorded CSF pressure. RESULTS: The sum total scores were significantly positively correlated with recorded CSF pressures. The positive correlation was seen when clinical and brain neuroimaging features were included alone, and the correlation was slightly stronger when venography features were included in addition. CONCLUSION: Calculating the sum total of clinical, brain neuroimaging and venography features (where venography is performed) present at initial presentation can help in the management of children under investigation for PTCS. Children with high scores are more likely to have severely raised CSF pressures and thus may warrant more urgent LP investigations. By contrast, in children with subtle abnormalities in optic disc appearance such that disc oedema cannot be ruled out, a low score may add further reassurance and less urgency to proceed to LP.

Predicting and interpreting identification errors in military vehicle training using multidimensional scaling.

We compared methods for predicting and understanding the source of confusion errors during military vehicle identification training. Participants completed training to identify main battle tanks. They also completed card-sorting and similarity-rating tasks to express their mental representation of resemblance across the set of training items. We expected participants to selectively attend to a subset of vehicle features during these tasks, and we hypothesised that we could predict identification confusion errors based on the outcomes of the card-sort and similarity-rating tasks. Based on card-sorting results, we were able to predict about 45% of observed identification confusions. Based on multidimensional scaling of the similarity-rating data, we could predict more than 80% of identification confusions. These methods also enabled us to infer the dimensions receiving significant attention from each participant. This understanding of mental representation may be crucial in creating personalised training that directs attention to features that are critical for accurate identification. PRACTITIONER SUMMARY: Participants completed military vehicle identification training and testing, along with card-sorting and similarity-rating tasks. The data enabled us to predict up to 84% of identification confusion errors and to understand the mental representation underlying these errors. These methods have potential to improve training and reduce identification errors leading to fratricide.

The tardigrade-derived mitochondrial abundant heat soluble protein improves adipose-derived stem cell survival against representative stressors.

Human adipose-derived stem cell (ASC) grafts have emerged as a powerful tool in regenerative medicine. However, ASC therapeutic potential is hindered by stressors throughout their use. Here we demonstrate the transgenic expression of the tardigrade-derived mitochondrial abundant heat soluble (MAHS) protein for improved ASC resistance to metabolic, mitochondrial, and injection shear stress. In vitro, MAHS-expressing ASCs demonstrate up to 61% increased cell survival following 72 h of incubation in phosphate buffered saline containing 20% media. Following up to 3.5% DMSO exposure for up to 72 h, a 14-49% increase in MAHS-expressing ASC survival was observed. Further, MAHS expression in ASCs is associated with up to 39% improved cell viability following injection through clinically relevant 27-, 32-, and 34-gauge needles. Our results reveal that MAHS expression in ASCs supports survival in response to a variety of common stressors associated with regenerative therapies, thereby motivating further investigation into MAHS as an agent for stem cell stress resistance. However, differentiation capacity in MAHS-expressing ASCs appears to be skewed in favor of osteogenesis over adipogenesis. Specifically, activity of the early bone formation marker alkaline phosphatase is increased by 74% in MAHS-expressing ASCs following 14 days in osteogenic media. Conversely, positive area of the neutral lipid droplet marker BODIPY is decreased by up to 10% in MAHS-transgenic ASCs following 14 days in adipogenic media. Interestingly, media supplementation with up to 40 mM glucose is sufficient to restore adipogenic differentiation within 14 days, prompting further analysis of mechanisms underlying interference between MAHS and differentiation processes.

A proposed framework for cerebral venous congestion.

BACKGROUND: While venous congestion in the peripheral vasculature has been described and accepted, intracranial venous congestion remains poorly understood. The characteristics, pathophysiology, and management of cerebral venous stasis, venous hypertension and venous congestion remain controversial, and a unifying conceptual schema is absent. The cerebral venous and lymphatic systems are part of a complex and dynamic interaction between the intracranial compartments, with interplay between the parenchyma, veins, arteries, cerebrospinal fluid, and recently characterized lymphatic-like systems in the brain. Each component contributes towards intracranial pressure, occupying space within the fixed calvarial volume. This article proposes a framework to consider conditions resulting in brain and neck venous congestion, and seeks to expedite further study of cerebral venous diagnoses, mechanisms, symptomatology, and treatments. METHODS: A multi-institution retrospective review was performed to identify unique patient cases, complemented with a published case series to assess a spectrum of disease states with components of venous congestion affecting the brain. These diseases were organized according to anatomical location and purported mechanisms. Outcomes of treatments were also analyzed. Illustrative cases were identified in the venous treatment databases of the authors. CONCLUSION: This framework is the first clinically structured description of venous pathologies resulting in intracranial venous and cerebrospinal fluid hypertension. Our proposed system highlights unique clinical symptoms and features critical for appropriate diagnostic work-up and potential treatment. This novel schema allows clinicians effectively to approach cases of intracranial hypertension secondary to venous etiologies, and furthermore provides a framework by which researchers can better understand this developing area of cerebrovascular disease.

Human factors and ergonomics assessment of food pantry work: A case study.

BACKGROUND: Research assessing work processes in food pantries has been limited to the client's experience and aspects of food donations [3-5]. Research on food pantries has yet to focus on understanding and evaluating worker-environment interaction. OBJECTIVE: The present case study examined the interaction between workers and their work environment while performing common tasks in a food pantry. METHODS: Data were collected through naturalistic observations and structured interviews. A task analysis was performed on the data. RESULTS: Several potential issues in the pantry were identified including with the workspace layout, environmental conditions, and signage. Human factors and ergonomics principles were then utilized to provide insights and recommendations (e.g., use of numbered rather than color-coded signage). CONCLUSIONS: Recommendations were provided to the case study food pantry for enhancing safety and productivity. Further research is needed to assess the generalizability of our findings to other food pantries.

Borderline Intracranial Hypertension Manifesting as Chronic Fatigue Syndrome Treated by Venous Sinus Stenting.

Chronic fatigue syndrome and cases of idiopathic intracranial hypertension without signs of raised intracranial pressure can be impossible to distinguish without direct measurement of intracranial pressure. Moreover, lumbar puncture, the usual method of measuring intracranial pressure, can produce a similar respite from symptoms in patients with chronic fatigue as it does in idiopathic intracranial hypertension. This suggests a connection between them, with chronic fatigue syndrome representing a forme fruste variant of idiopathic intracranial hypertension. If this were the case, then treatments available for idiopathic intracranial hypertension might be appropriate for chronic fatigue. We describe a 49-year-old woman with a long and debilitating history of chronic fatigue syndrome who was targeted for investigation of intracranial pressure because of headache, then diagnosed with borderline idiopathic intracranial hypertension after lumbar puncture and cerebrospinal fluid drainage. Further investigation showed narrowings at the anterior ends of the transverse sinuses, typical of those seen in idiopathic intracranial hypertension and associated with pressure gradients. Stenting of both transverse sinuses brought about a life-changing remission of symptoms with no regression in 2 years of follow-up. This result invites study of an alternative approach to the investigation and management of chronic fatigue.

Brain Slump Caused by Jugular Venous Stenoses Treated by Stenting: A Hypothesis to Link Spontaneous Intracranial Hypotension with Idiopathic Intracranial Hypertension.

Spontaneous intracranial hypotension, of which brain slump is an extreme expression, is caused by a cerebrospinal fluid leak. The reason the leak develops in the first place, however, is unknown, and some cases can be very difficult to manage. We describe a patient with severe symptoms of spontaneous intracranial hypotension and brain slump documented by magnetic resonance imaging whose clinical syndrome and structural brain anomaly resolved completely after treatment directed exclusively at improving cranial venous outflow. Diagnostics included computed tomography (CT) venography, catheter venography, and jugular venoplasty. CT venography showed narrowing of both internal jugular veins below the skull base. Catheter venography confirmed that these were associated with pressure gradients. Jugular venoplasty performed on two separate occasions as a clinical test gave temporary respite. Lasting remission (2 years of follow-up) was achieved by stenting the dominant internal jugular vein. These findings and this outcome suggest a mechanism for the development of spontaneous intracranial hypotension that would link it to idiopathic intracranial hypertension and have cranial venous outflow obstruction as the underlying cause.

Measuring carotid stenosis on contrast-enhanced magnetic resonance angiography: diagnostic performance and reproducibility of 3 different methods.

BACKGROUND AND PURPOSE: The aim of this study was to compare diagnostic performance and reproducibility of 3 different methods of quantifying stenosis on contrast-enhanced magnetic resonance angiography (CEMRA), with intra-arterial digital subtraction angiography (DSA) as the reference standard. METHODS: 167 symptomatic patients scheduled for DSA, after screening Doppler ultrasound, were prospectively recruited to undergo CEMRA. Severity of stenosis was measured according to the North American Symptomatic Trial Collaborators (NASCET), European Carotid Surgery Trial (ECST), and the common carotid (CC) methods. Measurements for each method were made for 284 vessels (142 included patients) on both CEMRA and DSA in a blinded and randomized manner by 3 independent attending neuroradiologists. RESULTS: Significant differences in prevalence of severe stenosis were seen with the 3 methods on both DSA and CEMRA, with ECST yielding the least and NASCET the most cases of severe stenosis. Overall, all 3 methods performed similarly well in terms of intermodality correlation and agreement. No significant differences in interobserver agreement were found on either modality. With CEMRA, however, we found a significantly lower sensitivity for detection of severe stenosis with ECST (79.8%) compared with NASCET (93.0%), with DSA as reference standard. CONCLUSIONS: Uniformity of carotid stenosis measurement methods is desirable because patient management may otherwise differ substantially. All 3 methods are adequate for use with DSA. With CEMRA, however, this study supports use of the NASCET method because of improved sensitivity for detecting severe stenosis.

Standardized whole brain mapping of tubers and subependymal nodules in tuberous sclerosis complex.

Tuberous sclerosis complex is associated with radiologically visible abnormalities of brain structure, principally tubers and subependymal nodules. We reviewed the literature on neuroimaging of tubers and subependymal nodules and found qualitative evidence of bilateral, predominantly frontal distribution of tubers and bilateral, predominantly subcortical distribution of subependymal nodules in prior studies of pediatric samples. We studied 25 high-functioning adults with tuberous sclerosis complex and normal IQ, acquiring both dual spin-echo and fluid-attenuated inversion recovery magnetic resonance imaging sequences to optimize radiologic diagnosis of tubers and nodules. Individual lesion maps were then coregistered in a standard stereotactic space to facilitate construction of lesion density maps and estimation of lesion density in cortical and subcortical regions reliably defined by a parcellated template image. We found the highest frequency of tubers in frontal lobes and the highest density of tubers in parietal regions. There was significant regional variation in tuber density but no significant lateralization of frequently bilateral tubers. Nodules were located predominantly in the caudate nucleus and were not significantly lateralized. Tuber and nodule volumes were significantly positively correlated. Tuber volume was larger, on average, in patients with a lifetime history of epilepsy, but there was no correlation between IQ and these measures of lesion load. Contemporary image processing tools can be used to enhance quantitative, whole brain analysis of lesion load in patients with tuberous sclerosis complex.

Spontaneous arteriovenous malformation of the external auditory meatus.

Arteriovenous malformations (AVM) of the head and neck are rare. They usually occur intracranially and derive their vascular supply from the intracranial vessels. In the English literature there has not been any documented case of AVMs in and around the external auditory meatus (EAM). The authors present the first case, a spontaneous AVM deriving its vascular supply from the posterior auricular artery. The diagnostic difficulties and management strategies of spontaneous AVMs are discussed.

Stent-Mediated Redistribution of Cerebral Venous Outflow in the Treatment of Severe Intractable Headache: A Case Report.

We describe a patient with multiple symptoms but whose primary complaint was of headache, in whom no firm diagnosis was made in two years, who was resistant to all treatment, until a markedly asymmetrical cranial venous outflow came to be regarded, not as normal variant anatomy but as fundamental to the clinical problem. Deliberately altering this anatomy in favour of a more symmetrical arrangement by stenting a hypoplastic transverse sinus brought about an immediate, profound and sustained clinical improvement. This result challenges the existing consensus on what is acceptable as normal in respect of cranial venous outflow. It raises intriguing questions about the relationship between neurological symptoms and the vagaries of cranial venous outflow anatomy. It suggests there may be new opportunities in the investigation of chronic headache.

What do lumbar puncture and jugular venoplasty say about a connection between chronic fatigue syndrome and idiopathic intracranial hypertension?

Introduction: Similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) invite speculation that they may be related. Cranial venous outflow obstruction plays a role in the development of IIH. Could it be a factor in chronic fatigue? This paper attempts to evaluate an investigative approach to chronic fatigue syndrome that allows for this possibility. Methods: Since 2007, patients attending a specialist clinic at our institution diagnosed with chronic fatigue syndrome and with prominent headache have been offered CT venography, lumbar puncture and a trial of cerebrospinal fluid withdrawal looking for IIH. Also, if CT venography revealed focal narrowing of the jugular veins, patients were offered catheter cerebral venography and jugular venoplasty attempting to establish their clinical significance. Results: In the 29 patients investigated to date, the mean cerebrospinal fluid (CSF) pressure was 19 cm H2O (range 12 - 41 cm H2O). Twenty-five patients responded positively to CSF withdrawal and in 5 the CSF pressures were high enough to allow an unequivocal diagnosis of IIH while in the remaining 20, symptoms improved with lumbar puncture even though CSF pressures were within the normal range. Twenty-one patients had focal narrowing of one or both internal jugular veins on CT venography. Fourteen of these have had jugular venoplasty, all of whom reported an improvement in symptoms afterwards lasting from a few minutes to more than 1 month. Conclusions: Chronic fatigue syndrome may represent an incomplete form of IIH. Cranial venous outflow obstruction deserves further investigation as a possible aetiological factor.

Maintenance of efficacy of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder: randomized-withdrawal study design.

OBJECTIVE: In this phase 3 extension study, the long-term maintenance of efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) was evaluated using a randomized-withdrawal study design. METHOD: European and US patients (6-17 years; N = 276) with ADHD were entered into a 26-week open-label trial of LDX treatment. Those who completed the open-label period (n = 157) were randomized 1:1 to their optimized dose of LDX (30, 50, or 70 mg per day) or placebo for a 6-week randomized-withdrawal period (RWP). The primary efficacy measure was the proportion of patients meeting treatment failure criteria (≥50% increase in ADHD Rating Scale IV total score and ≥2-point increase in Clinical Global Impressions-Severity of Illness [CGI-S] score, compared with RWP start point). Safety and tolerability were also evaluated. RESULTS: During the RWP (LDX, n = 78; placebo, n = 79), significantly fewer patients receiving LDX met treatment failure criteria (15.8%) compared with those receiving placebo (67.5%; difference = -51.7%; 95% confidence interval = -65.0, -38.5; p < .001 ). Most treatment failures occurred at or before the week 2 visit after randomization. Treatment-emergent adverse events were reported in 39.7% and 25.3% of patients receiving LDX and placebo, respectively, during the RWP. CONCLUSIONS: These data demonstrate the maintenance of efficacy of LDX during long-term treatment in children and adolescents with ADHD. The rapid return of symptoms on LDX withdrawal demonstrates the need for continuing treatment. The safety profile of LDX was consistent with that of other stimulants. Clinical trial registration information-Double-Blind, Placebo-Controlled, Randomized Withdrawal, Extension, Safety and Efficacy Study of LDX in Children and Adolescents Aged 6-17; http://clinicaltrials.gov; NCT00784654.

Looking for idiopathic intracranial hypertension in patients with chronic fatigue syndrome.

Introduction: Headache is common in chronic fatigue syndrome, a condition of unknown cause in which there are no clinical signs. Fatigue is common in idiopathic intracranial hypertension, a headache condition of unknown cause in which the only clinical signs are those of raised intracranial pressure, signs which may be absent. Might, therefore, idiopathic intracranial hypertension be present in some patients diagnosed with chronic fatigue syndrome? Could the two conditions be related? Patients and methods: From June 2007, patients attending a specialist clinic who fulfilled the diagnostic criteria for chronic fatigue syndrome and in whom headache was an especially prominent symptom were offered CT venography and lumbar puncture, looking for evidence of raised intracranial pressure. Results: Of the 20 patients who accepted lumbar puncture, eight had pressures of 20 cm H2O or greater, including three who had pressures of 25 cm H2O or greater. Mean pressure was 19 cm H2O. Conclusions: Some patients with headache and a diagnosis of chronic fatigue syndrome have unrecognised and occult idiopathic intracranial hypertension. The possibility that the two conditions are related cannot be excluded.

Lumbar puncture, chronic fatigue syndrome and idiopathic intracranial hypertension: a cross-sectional study.

OBJECTIVE: Unsuspected idiopathic intracranial hypertension (IIH) is found in a significant minority of patients attending clinics with named headache syndromes, if it is specifically sought out. Chronic fatigue syndrome is frequently associated with headache. Could the same be true of chronic fatigue? Moreover, there are striking similarities between the two conditions. Could they be related? Attempting to answer these questions, we describe the results of a change in clinical practice aimed at capturing patients with chronic fatigue who might have IIH. DESIGN: Cross-sectional. SETTING: Hospital outpatient and radiology departments. PARTICIPANTS: Patients attending a specialist clinic with chronic fatigue syndrome and headache who had lumbar puncture to exclude raised intracranial pressure. MAIN OUTCOME MEASURES: Intracranial pressure measured at lumbar puncture and the effect on headache of cerebrospinal fluid drainage. RESULTS: Mean cerebrospinal fluid pressure was 19 cm H2O (range 12-41 cm H2O). Four patients fulfilled the criteria for IIH. Thirteen others did not have pressures high enough to diagnose IIH but still reported an improvement in headache after drainage of cerebrospinal fluid. Some patients also volunteered an improvement in other symptoms, including fatigue. No patient had any clinical signs of raised intracranial pressure. CONCLUSIONS: An unknown, but possibly substantial, minority of patients with chronic fatigue syndrome may actually have IIH. An unknown, but much larger, proportion of patients with chronic fatigue syndrome do not have IIH by current criteria but respond to lumbar puncture in the same way as patients who do. This suggests that the two conditions may be related.

European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder.

This study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6-17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ≥ 28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70 mg/day), OROS-MPH (18, 36, or 54 mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 (95% confidence interval [CI]: -21.5 to -15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 (95% CI: -15.9 to -10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70-86), 14% (8-21), and 61% (51-70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital signs were modest and consistent with the known profile of LDX. LDX was effective and generally well tolerated in children and adolescents with ADHD.

A post hoc comparison of the effects of lisdexamfetamine dimesylate and osmotic-release oral system methylphenidate on symptoms of attention-deficit hyperactivity disorder in children and adolescents.

INTRODUCTION: There are limited head-to-head data comparing the efficacy of long-acting amfetamine- and methylphenidate-based psychostimulants as treatments for individuals with attention-deficit hyperactivity disorder (ADHD). This post hoc analysis provides the first parallel-group comparison of the effect of lisdexamfetamine dimesylate (lisdexamfetamine) and osmotic-release oral system methylphenidate (OROS-MPH) on symptoms of ADHD in children and adolescents. STUDY DESIGN: This was a post hoc analysis of a randomized, double-blind, parallel-group, dose-optimized, placebo-controlled, phase III study. SETTING: The phase III study was carried out in 48 centres across ten European countries. PATIENTS: The phase III study enrolled children and adolescents (aged 6-17 years) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for a primary diagnosis of ADHD and who had a baseline ADHD Rating Scale IV (ADHD-RS-IV) total score of 28 or higher. INTERVENTION: Eligible patients were randomized (1:1:1) to receive a once-daily, optimized dose of lisdexamfetamine (30, 50 or 70 mg/day), placebo or OROS-MPH (18, 36 or 54 mg/day) for 7 weeks. MAIN OUTCOME MEASURES: In this post hoc analysis, efficacy was assessed using the ADHD-RS-IV and Clinical Global Impressions-Improvement (CGI-I) scale. Responders were defined as those achieving at least a 30% reduction from baseline in ADHD-RS-IV total score and a CGI-I score of 1 (very much improved) or 2 (much improved). The proportion of patients achieving an ADHD-RS-IV total score less than or equal to the mean for their age (based on normative data) was also determined. Endpoint was the last on-treatment visit with a valid assessment. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs. RESULTS: Of the 336 patients randomized, 332 were included in the safety population, 317 were included in the full analysis set and 196 completed the study. The mean (standard deviation) ADHD-RS-IV total score at baseline was 40.7 (7.31) for lisdexamfetamine, 41.0 (7.14) for placebo and 40.5 (6.72) for OROS-MPH. The least-squares (LS) mean change (standard error) in ADHD-RS-IV total score from baseline to endpoint was -24.3 (1.16) for lisdexamfetamine, -5.7 (1.13) for placebo and -18.7 (1.14) for OROS-MPH. The difference between lisdexamfetamine and OROS-MPH in LS mean change (95% confidence interval [CI]) in ADHD-RS-IV total score from baseline to endpoint was statistically significant in favour of lisdexamfetamine (-5.6 [-8.4 to -2.7]; p < 0.001). The difference between lisdexamfetamine and OROS-MPH in the percentage of patients (95% CI) with a CGI-I score of 1 or 2 at endpoint was 17.4 (5.0-29.8; p < 0.05; number needed to treat [NNT] 6), and the difference in the percentage of patients (95% CI) achieving at least a 30% reduction in ADHD-RS-IV total score and a CGI-I score of 1 or 2 was 18.3 (5.4-31.3; p < 0.05; NNT 6). The difference between lisdexamfetamine and OROS-MPH in the percentage of patients (95% CI) with an ADHD-RS-IV total score less than or equal to the mean for their age at endpoint was 14.0 (0.6-27.4; p = 0.050). The overall frequency of TEAEs and the frequencies of decreased appetite, insomnia, decreased weight, nausea and anorexia TEAEs were greater in patients treated with lisdexamfetamine than in those treated with OROS-MPH, whereas headache and nasopharyngitis were more frequently reported in patients receiving OROS-MPH. CONCLUSIONS: This post hoc analysis showed that, at the doses tested, patients treated with lisdexamfetamine showed statistically significantly greater improvement in symptoms of ADHD than those receiving OROS-MPH, as assessed using the ADHD-RS-IV and CGI-I. The safety profiles of lisdexamfetamine and OROS-MPH were consistent with the known effects of stimulant medications.