Preferences related to attention-deficit/hyperactivity disorder and its treatment

Kate Van Brunt1, Louis S Matza1, Peter M Classi2, Joseph A Johnston21Center for Health Outcomes Research at United BioSource Corporation, Bethesda, MD, USA; 2Eli Lilly and Company, Indianapolis, IN, USAObjectives: A growing body of literature has highlighted the importance of considering patient preferences as part of the medical decision-making process. The purpose of the current review was to identify and summarize published research on preferences related to attention-deficit/hyperactivity disorder (ADHD) and its treatment, while suggesting directions for future research.Methods: A literature search identified 15 articles that included a choice-based assessment of preferences related to ADHD.Results: The 15 studies were grouped into four categories based on preference content: preference for a treatment directly experienced by the respondent or the respondent's child; preference for general treatment approaches; preference for a specific treatment attribute or outcome; and preference for aspects of ADHD-related treatment. Preference assessment methods ranged from global single items to detailed choice-based procedures, with few studies using rigorously developed assessment methods. Respondents included patients with ADHD, clinicians, parents, teachers, and survey respondents from the general population. Factors influencing preference include treatment characteristics, effectiveness for specific symptoms, side effects, and respondent demographics. Minimal research has examined treatment preferences of adults with ADHD.Discussion: Because there is no dominant treatment known to be the first choice for all patients, ADHD is a condition for which individual preferences can play an important role when making treatment decisions for individual patients. Given the potential role of preferences in clinical decision-making, more research is needed to better understand the preferences of patients with ADHD and other individuals who are directly affected by the disorder, such as parents and teachers.Keywords: patient preference, ADHD, parent preference, utilit

Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia

There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory-disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little of prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (3M:1F), in comparison with 21 consecutively recruited neurological memory-disordered patients and 14 healthy controls. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorised as: (i) fugue state, (ii) fugue-to-focal retrograde amnesia, (iii) psychogenic focal retrograde amnesia following a minor neurological episode, and (iv) patients with gaps in their memories. While neurological cases were characterised by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (p=0.012), perhaps reflecting a ‘learning episode’ predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognise the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time-periods, whereas the two focal retrograde amnesia groups showed a ‘reversed’ temporal gradient with relative sparing of recent memories. After 3-6 months, the fugue patients had improved to normal scores for facts and near-normal scores for events. By contrast, the two focal retrograde amnesia groups showed a lesser improvement and continued to show a reversed temporal gradient. In conclusion, the outcome in psychogenic amnesia, particularly those characterised by fugue, is better than generally supposed. Findings are interpreted in terms of Markowitsch’s and Kopelman’s models of psychogenic amnesia, and with respect to Anderson’s neuroimaging findings in memory inhibition

The role of pre-sleep cognitions in adolescent sleep-onset problems

© 2018 Elsevier BV. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (March 2018) in accordance with the publisher’s archiving policy.Study Objectives: To examine the relationship between pre-sleep cognitions and sleep-onset difficulties in an adolescent sample. Methods: Participants were 385 students (59% male) from grades 9 to 11, between 13 and 18 yrs old (M=15.6, SD=1.0), from 8 co-educational high schools of varied socioeconomic status in metropolitan Adelaide, South Australia. The cross-sectional study used a questionnaire battery including the Sleep Anticipatory Anxiety Questionnaire - Adolescent Version [SAAQ-A], completed during school time, followed by 8 days of sleep diary completion and wearing wrist actigraphy to obtain subjective and objective sleep onset latency [SOL]. Results: Significant relationships were found between somatic arousal (SAAQ-A subscale) and objective SOL, and between sleep-related cognitions (SAAQ-A subscale) and subjective SOL and SOL overestimation (sleep misperception). No relationships were found between subjective SOL and somatic or rehearsal and planning cognitions. Objective SOL was not related to rehearsal and planning, or sleep-related cognition scores, and sleep misperception had no relationship with somatic, and rehearsal and planning cognition scores. Conclusions: These findings are similar to those in clinical adult populations, but also notably different, for example the lack of association between negative sleep-related pre-sleep cognitions and objective sleep difficulty. This study’s results provide a basis for existing relationships between negative pre-sleep cognitions and subjective and objective sleep difficulties in this population to be examined causally in more detail

Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy

Deposition of amyloid beta (AB) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble A? from the brain. As CAA is associated with Alzheimer's disease and with intracerebral haemorrhage, the present study determines the unique sequence of changes that occur as A? accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, AB and smooth muscle actin and the immunostaining was analysed using Image J and confocal microscopy. Results showed that nidogen 2 (entactin) increases with age and decreases in CAA. Confocal microscopy revealed stages in the progression of CAA: AB initially deposits in basement membranes in the tunica media, replaces first the smooth muscle cells and then the connective tissue elements to leave artery walls completely or focally replaced by AB. The pattern of development of CAA in the human brain suggests expansion of AB from the basement membranes to progressively replace all tissue elements in the artery wall. Establishing this full picture of the development of CAA is pivotal in understanding the clinical presentation of CAA and for developing therapies to prevent accumulation of AB in artery walls. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock

Cognitive behavior therapy for comorbid Obsessive-Compulsive Disorder in high functioning Autism Spectrum Disorders:A randomized controlled trial

Background High rates of anxiety disorders, particularly obsessive compulsive disorder (OCD) are reported in people with Autism spectrum disorders (ASD). Group cognitive behavioral treatment (CBT) has been found effective for anxiety in young people with ASD but not been OCD specific. One uncontrolled pilot study of individual CBT for OCD for adults with ASD showed good treatment efficacy. Methods Forty-six adolescents and adults (mean age 26.9 years, 35 Males) with ASD and comorbid OCD were randomized to CBT for OCD or anxiety management (AM), a plausible control treatment. Treatments were matched in duration (mean of 17.4 sessions CBT; 14.4 sessions AM), the Yale–Brown Obsessive Compulsive Severity Scale (YBOCS) as primary outcome measure and evaluations blind to treatment group. Treatment response was defined as > 25% reduction in YBOCS total severity scores. Results Both treatments produced a significant reduction in OCD symptoms, within-group effect sizes of 1.01 CBT group and 0.6 for the AM group. There were no statistically significant differences between the two groups at end of treatment, although more responders in the CBT group (45 versus 20%). Effect sizes for self-rated improvement were small (0.33 CBT group; –0.05 AM group). Mild symptom severity was associated with improvement in the AM but not the CBT group. Family/carer factors were important for both groups, in that increased family accommodation was associated with poorer outcome. Conclusions Evidence-based psychological interventions, both AM and CBT, were effective in treating comorbid OCD in young people and adults with ASD

A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma.

PURPOSE: Patients with recurrent high-grade gliomas (HGG) are usually managed with alkylating chemotherapy ± bevacizumab. However, prognosis remains very poor. Preclinically, we showed that HGGs are a target for arginine depletion with pegargiminase (ADI-PEG20) due to epimutations of argininosuccinate synthetase (ASS1) and/or argininosuccinate lyase (ASL). Moreover, ADI-PEG20 disrupts pyrimidine pools in ASS1-deficient HGGs, thereby impacting sensitivity to the antifolate, pemetrexed. PATIENTS AND METHODS: We expanded a phase I trial of ADI-PEG20 with pemetrexed and cisplatin (ADIPEMCIS) to patients with ASS1-deficient recurrent HGGs (NCT02029690). Patients were enrolled (01/16-06/17) to receive weekly ADI-PEG20 36 mg/m2 intramuscularly plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 intravenously once every 3 weeks for up to 6 cycles. Patients with disease control were allowed ADI-PEG20 maintenance. The primary endpoints were safety, tolerability, and preliminary estimates of efficacy. RESULTS: Ten ASS1-deficient heavily pretreated patients were treated with ADIPEMCIS therapy. Treatment was well tolerated with the majority of adverse events being Common Terminology Criteria for Adverse Events v4.03 grade 1-2. The best overall response was stable disease in 8 patients (80%). Plasma arginine was suppressed significantly below baseline with a reciprocal increase in citrulline during the sampling period. The anti-ADI-PEG20 antibody titer rose during the first 4 weeks of treatment before reaching a plateau. Median progression-free survival (PFS) was 5.2 months (95% confidence interval (CI), 2.5-20.8) and overall survival was 6.3 months (95% CI, 1.8-9.7). CONCLUSIONS: In this recurrent HGG study, ADIPEMCIS was well tolerated and compares favorably to historical controls. Additional trials of ADI-PEG20 in HGG are planned

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Train Smart Study: protocol for a randomised trial investigating the role of exercise training dose on markers of brain health in sedentary middle-aged adults

Introduction Regular aerobic exercise is associated with improved cognitive function, implicating it as a strategy to reduce dementia risk. This is reinforced by the association between greater cardiorespiratory fitness and larger brain volume, superior cognitive performance and lower dementia risk. However, the optimal aerobic exercise dose, namely the intensity and mode of delivery, to improve brain health and lower dementia risk has received less attention. We aim to determine the effect of different doses of aerobic exercise training on markers of brain health in sedentary middle-aged adults, hypothesising that high-intensity interval training (HIIT) will be more beneficial than moderate-intensity continuous training (MICT). Methods and analysis In this two-group parallel, open-label blinded endpoint randomised trial, 70 sedentary middle-aged (45-65 years) adults will be randomly allocated to one of two 12-week aerobic exercise training interventions matched for total exercise training volume: (1) MICT (n=35) or HIIT (n=35). Participants will perform ∼50 min exercise training sessions, 3 days per week, for 12 weeks. The primary outcome will be measured as between-group difference in cardiorespiratory fitness (peak oxygen uptake) change from baseline to the end of training. Secondary outcomes include between-group differences in cognitive function and ultra-high field MRI (7T) measured markers of brain health (brain blood flow, cerebrovascular function, brain volume, white matter microstructural integrity and resting state functional brain activity) changes from baseline to the end of training. Ethics and dissemination The Victoria University Human Research Ethics Committee (VUHREC) has approved this study (HRE20178), and all protocol modifications will be communicated to the relevant parties (eg, VUHREC, trial registry). Findings from this study will be disseminated via peer-review publications, conference presentations, clinical communications and both mainstream and social media. Trial registration number ANZCTR12621000144819

Baseline factors predictive of serious suicidality at follow-up: findings focussing on age and gender from a community-based study

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-244X/10/41Background: Although often providing more reliable and informative findings relative to other study designs, longitudinal investigations of prevalence and predictors of suicidal behaviour remain uncommon. This paper compares 12-month prevalence rates for suicidal ideation and suicide attempt at baseline and follow-up; identifies new cases and remissions; and assesses the capacity of baseline data to predict serious suicidality at follow-up, focusing on age and gender differences. Methods: 6,666 participants aged 20-29, 40-49 and 60-69 years were drawn from the first (1999-2001) and second (2003-2006) waves of a general population survey. Analyses involved multivariate logistic regression. Results: At follow-up, prevalence of suicidal ideation and suicide attempt had decreased (8.2%-6.1%, and 0.8%-0.5%, respectively). However, over one quarter of those reporting serious suicidality at baseline still experienced it four years later. Females aged 20-29 never married or diagnosed with a physical illness at follow-up were at greater risk of serious suicidality (OR = 4.17, 95% CI = 3.11-5.23; OR = 3.18, 95% CI = 2.09-4.26, respectively). Males aged 40-49 not in the labour force had increased odds of serious suicidality (OR = 4.08, 95% CI = 1.6-6.48) compared to their equivalently-aged and employed counterparts. Depressed/anxious females aged 60-69 were nearly 30% more likely to be seriously suicidal. Conclusions: There are age and gender differentials in the risk factors for suicidality. Life-circumstances contribute substantially to the onset of serious suicidality, in addition to symptoms of depression and anxiety. These findings are particularly pertinent to the development of effective population-based suicide prevention strategies.A Kate Fairweather-Schmidt, Kaarin J Anstey, Agus Salim and Bryan Rodger