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Sample records for lisdexamfetamine dimesylate ldx

  1. Expert recommendation: contributions to clinical practice of the new prodrug lisdexamfetamine dimesylate (LDX) in the treatment of attention deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Alda, José A; Soutullo, César; Ramos-Quiroga, Josep A; Quintero, Javier; Hervás, Amaia; Hernández-Otero, Isabel; Sans-Fitó, Anna; Cardo-Jalón, Esther Cardo-Jalón; Fernández-Jaén, Alberto; Fernández-Pérez, Maximino; Hidalgo-Vicario, M Inés; Eddy-Ives, Lefa S; Sánchez, Javier

    2014-12-01

    Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobiological disorders in childhood, and is characterized by inappropriate levels of inattention, hyperactivity and/or impulsiveness, with an estimated prevalence of 5.29%. ADHD can have a negative impact upon all areas of the life of the patient. The main clinical guides accept multimodal treatment, involving both pharmacological and psychological measures, as the best management approach in ADHD (psychoeducational, behavioural and academic). Lisdexamfetamine dimesylate (LDX) is a new drug for the treatment of ADHD. A multidiscipline expert document has been developed, compiling the scientific evidence referred to this new molecule. The study also addresses the existing shortcomings in current drug therapy for ADHD and the contributions of LDX to routine clinical practice, in an attempt to help and guide physicians in the use of this new treatment. This document is endorsed by the ADHD and Psychoeducational Development task Group of the Spanish Society of Primary Care Pediatrics (Grupo de TDAH y Desarrollo Psicoeducativo de la Asociación Española de Pediatría de Atención Primaria, AEPap), the Spanish Society of Pediatric Neurology (Sociedad Española de Neurología Pediátrica, SENEP) and the Spanish Society of Out-hospital Pediatrics and Primary Care (Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria, SEPEAP).

  2. A Systematic Review of the Safety of Lisdexamfetamine Dimesylate

    OpenAIRE

    Coghill, David R.; Caballero, Beatriz; Sorooshian, Shaw; Civil, Richard

    2014-01-01

    Background Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). Methods A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). Results In short-term, parallel-group...

  3. Efficacy and Safety of Lisdexamfetamine Dimesylate in Adolescents with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Findling, Robert L.; Childress, Ann C.; Cutler, Andrew J.; Gasior, Maria; Hamdani, Mohamed; Ferreira-Cornwell, M. Celeste; Squires, Liza

    2011-01-01

    Objective: To examine lisdexamfetamine dimesylate (LDX) efficacy and safety versus placebo in adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: Adolescents (13 through 17) with at least moderately symptomatic ADHD (ADHD Rating Scale IV: Clinician Version [ADHD-RS-IV] score greater than or equal to 28) were randomized to…

  4. Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

    Science.gov (United States)

    Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

    2012-01-01

    Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

  5. Reading Performance as a Function of Treatment with Lisdexamfetamine Dimesylate in Elementary School Children Diagnosed with ADHD

    Science.gov (United States)

    Wigal, Sharon B.; Maltas, Stephanie; Crinella, Francis; Stehli, Annamarie; Steinhoff, Kenneth; Lakes, Kimberley; Schuck, Sabrina

    2012-01-01

    Background: Medication treatment studies of ADHD have typically not assessed effects on reading performance, although reading difficulties frequently co-occur in children with ADHD. The current study characterizes the effects of lisdexamfetamine dimesylate (LDX; Vyvanse[R], Shire US Inc.), at peak efficacy, on reading performance in children with…

  6. Lisdexamfetamine Dimesylate Effects on Binge Eating Behaviour and Obsessive-Compulsive and Impulsive Features in Adults with Binge Eating Disorder.

    Science.gov (United States)

    McElroy, Susan L; Mitchell, James E; Wilfley, Denise; Gasior, Maria; Ferreira-Cornwell, M Celeste; McKay, Michael; Wang, Jiannong; Whitaker, Timothy; Hudson, James I

    2016-05-01

    In a published 11-week, placebo-controlled trial, 50 and 70 mg/d lisdexamfetamine dimesylate (LDX), but not 30 mg/d LDX, significantly reduced binge eating days (primary endpoint) in adults with binge eating disorder (BED). This report provides descriptions of LDX effects on secondary endpoints (Binge Eating Scale [BES]; Three-Factor Eating Questionnaire [TFEQ]; Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE]; and the Barratt Impulsiveness Scale, version 11 [BIS-11]) from that study. Week 11 least squares mean treatment differences favoured all LDX doses over placebo on the BES (p ≤ 0.03), TFEQ Disinhibition and Hunger subscales (all p binge eating severity and obsessive-compulsive and impulsive features of BED in addition to binge eating days. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

  7. A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Childress Ann C

    2009-06-01

    Full Text Available Abstract Background Lisdexamfetamine dimesylate (LDX is indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD in children 6 to 12 years of age and in adults. In a previous laboratory school study, LDX demonstrated efficacy 2 hours postdose with duration of efficacy through 12 hours. The current study further characterizes the time course of effect of LDX. Methods Children aged 6 to 12 years with ADHD were enrolled in a laboratory school study. The multicenter study consisted of open-label, dose-optimization of LDX (30, 50, 70 mg/d, 4 weeks followed by a randomized, placebo-controlled, 2-way crossover phase (1 week each. Efficacy measures included the SKAMP (deportment [primary] and attention [secondary] and PERMP (attempted/correct scales (secondary measured at predose and at 1.5, 2.5, 5, 7.5, 10, 12, and 13 hours postdose. Safety measures included treatment-emergent adverse events (AEs, physical examination, vital signs, and ECGs. Results A total of 117 subjects were randomized and 111 completed the study. Compared with placebo, LDX demonstrated significantly greater efficacy at each postdose time point (1.5 hours to 13.0 hours, as measured by SKAMP deportment and attention scales and PERMP (P Conclusion In school-aged children (6 to 12 years with ADHD, efficacy of LDX was maintained from the first time point (1.5 hours up to the last time point assessed (13.0 hours. LDX was generally well tolerated, resulting in typical stimulant AEs. Trial registration Official Title: A Phase IIIb, Randomized, Double-Blind, Multi-Center, Placebo-Controlled, Dose-Optimization, Cross-Over, Analog Classroom Study to Assess the Time of Onset of Vyvanse (Lisdexamfetamine Dimesylate in Pediatric Subjects Aged 6–12 With Attention-Deficit/Hyperactivity Disorder. ClinicalTrials.gov Identifier: NCT00500149 http://clinicaltrials.gov/ct2/show/NCT00500149

  8. Treatment outcomes after methylphenidate in adults with attention-deficit/hyperactivity disorder treated with lisdexamfetamine dimesylate or atomoxetine

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    Joseph A

    2016-03-01

    Full Text Available Alain Joseph,1 Martin Cloutier,2 Annie Guérin,2 Roy Nitulescu,2 Vanja Sikirica3 1Global HEOR and Epidemiology, Shire, Zählerweg, Zug, Switzerland; 2Analysis Group, Inc., Montreal, Quebec, Canada; 3Global HEOR and Epidemiology, Shire, Wayne, PA, USA Purpose: To compare treatment adherence, discontinuation, add-on, and daily average consumption (DACON among adults with attention-deficit/hyperactivity disorder receiving second-line lisdexamfetamine dimesylate (LDX or atomoxetine (ATX, following methylphenidate.Patients and methods: A retrospective cohort study using US commercial claims databases (Q2/2009–Q3/2013.Results: At month 12, the LDX cohort (N=2,718 had a higher adherence level (proportion of days covered: 0.48 versus 0.30, P<0.001 and was less likely to discontinue (Kaplan–Meier estimate: 63% versus 85%, P<0.001 than the ATX cohort (N=674. There were no statistical differences in treatment add-on rates between cohorts (Kaplan–Meier estimate: 26% versus 25%, P=0.297. The LDX cohort had a lower DACON (1.10 versus 1.31, P<0.001 and was less likely to have a DACON >1 (adjusted odds ratio: 0.20, 95% confidence interval: 0.15–0.25, P<0.001 than the ATX cohort.Conclusion: Adults with attention-deficit/hyperactivity disorder treated with LDX following methylphenidate had a higher treatment adherence and lower discontinuation and DACON relative to those treated with ATX following methylphenidate. Keywords: ADHD, adult, adherence, lisdexamfetamine dimesylate, atomoxetine

  9. Effect of lisdexamfetamine dimesylate on sleep in adults with attention-deficit/hyperactivity disorder

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    Weisler Richard

    2009-08-01

    Full Text Available Abstract Background Sleep problems are common in adults with attention-deficit/hyperactivity disorder (ADHD. This analysis aimed to evaluate the impact of lisdexamfetamine dimesylate (LDX on sleep quality in adults with ADHD. Methods This 4-week, phase 3, double-blind, forced-dose escalation study of adults aged 18 to 55 years with ADHD randomized participants to receive placebo (n = 62, or 30 (n = 119, 50 (n = 117, or 70 (n = 122 mg/d LDX, taken once a day in the morning. The self-rated Pittsburgh Sleep Quality Index (PSQI was administered at baseline and at week 4 to assess sleep quality. The PSQI global score assesses 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction each scored from 0 (no difficulty to 3 (severe difficulty. Results The mean baseline PSQI global score was 5.8 for LDX and 6.3 for placebo (P = .19 indicating poor overall sleep quality. At endpoint, least squares (LS mean change from baseline was -0.8 for LDX vs -0.5 for placebo (P = .33. The daytime functioning component showed significant improvement in LS mean change at endpoint for LDX compared with placebo (LDX -0.4 vs placebo 0.0, P = .0001. LS mean changes for the other 6 PSQI components did not significantly differ from placebo. Sleep-related treatment-emergent adverse events with an incidence ≥2% in the active treatment and placebo groups, respectively, were insomnia (19.3% and 4.8%, initial insomnia (5.0% and 3.2%, middle insomnia (3.6% and 0%, sleep disorder (0.6% and 3.2%, somnolence (0.3% and 3.2%, and fatigue (4.7% and 4.8%, and were generally mild or moderate in severity. Conclusion For most subjects, LDX was not associated with an overall worsening of sleep quality and significantly improved daytime functioning in adults with ADHD. Trial Registration clinicaltrials.gov Identifier: NCT00334880

  10. Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design

    Directory of Open Access Journals (Sweden)

    Gao Joseph

    2010-06-01

    Full Text Available Abstract Background Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX was assessed in adults (18-55 years with attention-deficit/hyperactivity disorder (ADHD using the simulated adult workplace environment. Methods After open-label dose optimization (4-week with LDX, 30-70 mg/d, subjects entered a 2-week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP total score (attempted+correct measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary and at each time point vs placebo (secondary, and ADHD Rating Scale IV (ADHD-RS-IV with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs, vital signs, and electrocardiograms. Results Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P P ≤ .0017 for each time point and change from predose (P P Conclusions LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours to last (14 hours postdose time point vs placebo in adults with ADHD. Trial Registration ClinicalTrials.gov Identifier: NCT00697515 Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX in Adults With Attention-Deficit Hyperactivity Disorder (ADHD http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1

  11. Efficacy of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder previously treated with methylphenidate: a post hoc analysis

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    Jain Rakesh

    2011-11-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide. Stimulants (methylphenidate [MPH] and amphetamine are considered first-line ADHD pharmacotherapy. MPH is a catecholamine reuptake inhibitor, whereas amphetamines have additional presynaptic activity. Although MPH and amphetamine can effectively manage ADHD symptoms in most pediatric patients, many still fail to respond optimally to either. After administration, the prodrug stimulant lisdexamfetamine dimesylate (LDX is converted to l-lysine and therapeutically active d-amphetamine in the blood. The objective of this study was to evaluate the clinical efficacy of LDX in children with ADHD who remained symptomatic (ie, nonremitters; ADHD Rating Scale IV [ADHD-RS-IV] total score > 18 on MPH therapy prior to enrollment in a 4-week placebo-controlled LDX trial, compared with the overall population. Methods In this post hoc analysis of data from a multicenter, randomized, double-blind, forced-dose titration study, we evaluated the clinical efficacy of LDX in children aged 6-12 years with and without prior MPH treatment at screening. ADHD symptoms were assessed using the ADHD-RS-IV scale, Conners' Parent Rating Scale-Revised short form (CPRS-R, and Clinical Global Impressions-Improvement scale, at screening, baseline, and endpoint. ADHD-RS-IV total and CPRS-R ADHD Index scores were summarized as mean (SD. Clinical response for the subgroup analysis was defined as a ≥ 30% reduction from baseline in ADHD-RS-IV score and a CGI-I score of 1 or 2. Dunnett test was used to compare change from baseline in all groups. Number needed to treat to achieve one clinical responder or one symptomatic remitter was calculated as the reciprocal of the difference in their proportions on active treatment and placebo at endpoint. Results Of 290 randomized participants enrolled, 28

  12. Time course of the effects of lisdexamfetamine dimesylate in two phase 3, randomized, double-blind, placebo-controlled trials in adults with binge-eating disorder.

    Science.gov (United States)

    McElroy, Susan L; Hudson, James I; Gasior, Maria; Herman, Barry K; Radewonuk, Jana; Wilfley, Denise; Busner, Joan

    2017-08-01

    This study examined the time course of efficacy-related endpoints for lisdexamfetamine dimesylate (LDX) versus placebo in adults with protocol-defined moderate to severe binge-eating disorder (BED). In two 12-week, double-blind, placebo-controlled studies, adults meeting DSM-IV-TR BED criteria were randomized 1:1 to receive placebo or dose-optimized LDX (50 or 70 mg). Analyses across visits used mixed-effects models for repeated measures (binge eating days/week, binge eating episodes/week, Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE] scores, percentage body weight change) and chi-square tests (Clinical Global Impressions-Improvement [CGI-I; from the perspective of BED symptoms] scale dichotomized as improved or not improved). These analyses were not part of the prespecified testing strategy, so reported p values are nominal (unadjusted and descriptive only). Least squares mean treatment differences for change from baseline in both studies favored LDX over placebo (all nominal p values binge eating days/week, binge-eating episodes/week, and percentage weight change and at the first posttreatment assessment (Week 4) for Y-BOCS-BE total and domain scores. On the CGI-I, more participants on LDX than placebo were categorized as improved starting at Week 1 in both studies (both nominal p values Eating Disorders Published by Wiley Periodicals, Inc.

  13. Time course of the effects of lisdexamfetamine dimesylate in two phase 3, randomized, double‐blind, placebo‐controlled trials in adults with binge‐eating disorder

    Science.gov (United States)

    Hudson, James I.; Gasior, Maria; Herman, Barry K.; Radewonuk, Jana; Wilfley, Denise; Busner, Joan

    2017-01-01

    Abstract Objective This study examined the time course of efficacy‐related endpoints for lisdexamfetamine dimesylate (LDX) versus placebo in adults with protocol‐defined moderate to severe binge‐eating disorder (BED). Methods In two 12‐week, double‐blind, placebo‐controlled studies, adults meeting DSM‐IV‐TR BED criteria were randomized 1:1 to receive placebo or dose‐optimized LDX (50 or 70 mg). Analyses across visits used mixed‐effects models for repeated measures (binge eating days/week, binge eating episodes/week, Yale‐Brown Obsessive Compulsive Scale modified for Binge Eating [Y‐BOCS‐BE] scores, percentage body weight change) and chi‐square tests (Clinical Global Impressions—Improvement [CGI‐I; from the perspective of BED symptoms] scale dichotomized as improved or not improved). These analyses were not part of the prespecified testing strategy, so reported p values are nominal (unadjusted and descriptive only). Results Least squares mean treatment differences for change from baseline in both studies favored LDX over placebo (all nominal p values binge eating days/week, binge‐eating episodes/week, and percentage weight change and at the first posttreatment assessment (Week 4) for Y‐BOCS‐BE total and domain scores. On the CGI‐I, more participants on LDX than placebo were categorized as improved starting at Week 1 in both studies (both nominal p values <  .001). Across these efficacy‐related endpoints, the superiority of LDX over placebo was maintained at each posttreatment assessment in both studies (all nominal p values <  .001). Discussion In adults with BED, LDX treatment appeared to be associated with improvement on efficacy measures as early as 1 week, which was maintained throughout the 12‐week studies. PMID:28481434

  14. An update on lisdexamfetamine dimesylate for the treatment of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Wigal, Sharon B; Raja, Pooja; Shukla, Ankita

    2013-01-01

    The efficacy and safety of stimulants for the pharmacologic management of attention deficit hyperactivity disorder (ADHD) is well documented. The US Food and Drug Administration approval of additional classes of medication even within stimulant treatments expands the prescribing options for practitioners. The focus of this paper is the prodrug amphetamine stimulant, lisdexamfetamine (LDX) , which is an example of such an agent with a novel delivery system. This review covers the proof-of-concept and later studies of LDX to describe its use to treat ADHD in pediatric and adult populations. A literature search and review of LDX were carried out using the PubMed database up to August 2012. Clinical studies of LDX in children and adults with ADHD demonstrate its tolerability and its efficacy in reducing ADHD symptoms. Future research should be less restrictive in order to address some of the unmet needs in ADHD treatment. The inclusion of patients with ADHD and co-occurring mental health disorders and/or medical conditions is typically not studied in clinical trials nor is the prior ADHD treatment exposure of study participants. The preschool age population also is understudied in recently approved ADHD treatments such as LDX. Finally, how to approach the treatment of participants or first-degree relatives with a medical history or presence of substance use disorder presents an ongoing clinical challenge.

  15. Functional outcomes from a head-to-head, randomized, double-blind trial of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder and an inadequate response to methylphenidate.

    Science.gov (United States)

    Nagy, Peter; Häge, Alexander; Coghill, David R; Caballero, Beatriz; Adeyi, Ben; Anderson, Colleen S; Sikirica, Vanja; Cardo, Esther

    2016-02-01

    Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in multiple domains of patients' lives. A secondary objective of this randomized, active-controlled, head-to-head, double-blind, dose-optimized clinical trial was to compare the effects of lisdexamfetamine dimesylate (LDX) and atomoxetine (ATX) on functional impairment in children and adolescents with ADHD. Patients aged 6-17 years with an ADHD Rating Scale IV total score ≥ 28 and an inadequate response to methylphenidate treatment (judged by investigators) were randomized (1:1) to once-daily LDX or ATX for 9 weeks. Parents/guardians completed the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at baseline and at week 9 or early termination. p values were nominal and not corrected for multiple comparisons. Of 267 randomized patients, 200 completed the study (LDX 99, ATX 101). At baseline, mean WFIRS-P total score in the LDX group was 0.95 [standard deviation (SD) 0.474; 95% confidence interval (CI) 0.87, 1.03] and in the ATX group was 0.91 (0.513; 0.82, 1.00). Scores in all WFIRS-P domains improved from baseline to endpoint in both groups, with least-squares mean changes in total score of -0.35 (95% CI -0.42, -0.29) for LDX and -0.27 (-0.33, -0.20) for ATX. The difference between LDX and ATX was statistically significant (p ADHD; LDX was statistically significantly more effective than ATX in two of six domains and in total score.

  16. Efficacy and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: sex and age effects and effect size across the day

    Directory of Open Access Journals (Sweden)

    Childress Ann C

    2010-12-01

    Full Text Available Abstract Background Efficacy and safety profiles by sex and age (6-9 vs 10-12 years and magnitude and duration of effect by effect size overall and across the day of lisdexamfetamine dimesylate (LDX vs placebo were assessed. Methods This study enrolled children (6-12 years with attention-deficit/hyperactivity disorder (ADHD in an open-label dose optimization with LDX (30-70 mg/d followed by a randomized, double-blind, placebo-controlled, 2-way crossover phase. Post hoc analyses assessed interaction between sex or age and treatment and assessed effect sizes for Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP and Permanent Product Measure of Performance (PERMP scales and ADHD Rating Scale IV measures. No corrections for multiple testing were applied on time points and subgroup statistical comparisons. Results 129 participants enrolled; 117 randomized. Both sexes showed improvement on all assessments at postdose time points; females showed less impairment than males for SKAMP and PERMP scores in treatment and placebo groups at nearly all times. Both age groups improved on all assessments at postdose time points. Children 10-12 years had less impairment in SKAMP ratings than those 6-9 years. Treatment-by-sex interactions were observed at time points for SKAMP-D, SKAMP total, and PERMP scores; no consistent pattern across scales or time points was observed. LDX demonstrated significant improvement vs placebo, by effect size, on SKAMP-D from 1.5-13 hours postdose. The overall LS mean (SE SKAMP-D effect size was -1.73 (0.18. In the dose-optimization phase, common (≥2% treatment-emergent adverse events (TEAEs in males were upper abdominal pain, headache, affect lability, initial insomnia, and insomnia; in females were nausea and decreased weight. During the crossover phase for those taking LDX, higher incidence (≥2% greater was observed in males for upper abdominal pain and insomnia and in females for nausea and headache. Overall incidence of

  17. Open-label administration of lisdexamfetamine dimesylate improves executive function impairments and symptoms of attention-deficit/hyperactivity disorder in adults.

    Science.gov (United States)

    Brown, Thomas E; Brams, Matthew; Gao, Joseph; Gasior, Maria; Childress, Ann

    2010-09-01

    Executive function (EF) impairment in attention-deficit/hyperactivity disorder (ADHD) may account for behavioral symptoms such as poor concentration, impaired working memory, problems in shifting among tasks, and prioritizing and planning complex sets of tasks or completing long-term projects at work or school. Poor self-regulation and control of emotional behaviors frequently are seen in patients with ADHD. This study assessed EF behaviors in adults with ADHD at baseline and after 4 weeks of treatment with lisdexamfetamine dimesylate (LDX). Executive function behavior was assessed using the Brown Attention-Deficit Disorder Scale (BADDS) during the 4-week open-label dose-optimization phase prior to a 2-period, randomized, double-blind, placebo-controlled crossover study of LDX (30-70 mg/day). The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts assessed ADHD symptoms. Change in EF behavioral symptoms was evaluated based on week 4 BADDS total and cluster scores; analyses of shifts from baseline among subjects with BADDS scores < 50, 50 to 59, 60 to 69, and ≥ 70; and scores less than or greater than baseline 90% confidence range (eg, reliably improved or worsened, respectively). Treatment-emergent adverse events (TEAEs) were described. At week 4, BADDS total and cluster scores were reduced (ie, improved; all P < 0.0001 vs baseline [n = 127]). The ADHD-RS-IV with adult prompts scores also improved (all P < 0.0001 vs baseline). At week 4, 62.7% of subjects had a BADDS total score of < 50, and 78.9% were reliably improved; 1.4% were reliably worsened. Common TEAEs (≥ 5%) during the dose-optimization phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), insomnia (18.3%), upper respiratory tract infection (9.9%), irritability (8.5%), nausea (7.7%), anxiety (5.6%), and feeling jittery (5.6%). Clinically optimized doses of LDX (30-70 mg/day) significantly improved EF behaviors in adults with ADHD. Treatment-emergent adverse events with LDX were

  18. Development, validation and comparison of two stability-indicating RP-LC methods using charged aerosol and UV detectors for analysis of lisdexamfetamine dimesylate in capsules

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    Graciela Carlos

    2016-11-01

    Full Text Available Two new stability-indicating liquid chromatographic methods using two detectors, an ultraviolet (UV and a charged aerosol detector (CAD simultaneously connected in series were validated for the assessment of lisdexamfetamine dimesylate (LDX in capsule. The method was optimized and the influence of individual parameters on UV and CAD response and sensitivity was studied. Chromatography was performed on a Zorbax CN column (250 mm × 4.6 mm, 5 μm in an isocratic elution mode, using acetonitrile and 20 mM ammonium formate at pH 4.0 (50:50, v/v as mobile phase and UV detection at 207 nm. The developed method was validated according to ICH guidelines and the parameters’ specificity, limit of detection, limit of quantitation, linearity, accuracy, precision and robustness were evaluated. CAD is designated to be a non-linear detector in a wide dynamic range, however, the method was linear over the concentration range of 70–130 μg mL−1 in both detectors. The method was precise and accurate. Robustness study was performed by a Plackett–Burman design, delivering results within the acceptable range. Neither the excipients nor the degradation products showed interference in the method after studies of specificity as well as under stress conditions. The results of the LC-UV and LC-CAD methods were statistically compared through ANOVA and showed no significant difference (p > 0.05. Both proposed methods could be considered interchangeable and stability-indicating, and can be applied as an appropriate quality control tool for routine analysis of LDX in capsule.

  19. Self-Reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study.

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    Adler, Lenard A; Dirks, Bryan; Deas, Patrick; Raychaudhuri, Aparna; Dauphin, Matthew; Saylor, Keith; Weisler, Richard

    2013-10-09

    This study examined the effects of lisdexamfetamine dimesylate (LDX) on quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) and clinically significant executive function deficits (EFD). This report highlights QOL findings from a 10-week randomized placebo-controlled trial of LDX (30-70 mg/d) in adults (18-55 years) with ADHD and EFD (Behavior Rating Inventory of EF-Adult, Global Executive Composite [BRIEF-A GEC] ≥65). The primary efficacy measure was the self-reported BRIEF-A; a key secondary measure was self-reported QOL on the Adult ADHD Impact Module (AIM-A). The clinician-completed ADHD Rating Scale version IV (ADHD-RS-IV) with adult prompts and Clinical Global Impressions-Severity (CGI-S) were also employed. The Adult ADHD QoL (AAQoL) was added while the study was in progress. A post hoc analysis examined the subgroup having evaluable results from both AIM-A and AAQoL. Of 161 randomized (placebo, 81; LDX, 80), 159 were included in the safety population. LDX improved AIM-A multi-item domain scores versus placebo; LS mean difference for Performance and Daily Functioning was 21.6 (ES, 0.93, PPsychological Health was 12.1; Life Outlook was 12.5; and Relationships was 7.3. In a post hoc analysis of participants with both AIM-A and AAQoL scores, AIM-A multi-item subgroup analysis scores numerically improved with LDX, with smaller difference for Impact of Symptoms: Daily Interference. The safety profile of LDX was consistent with amphetamine use in previous studies. Overall, adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A and AAQoL scales in line with medium/large ES; these improvements were paralleled by improvements in EF and ADHD symptoms. The safety profile of LDX was similar to previous studies. ClinicalTrials.gov, NCT01101022.

  20. Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial

    Directory of Open Access Journals (Sweden)

    Coghill DR

    2014-10-01

    Full Text Available David R Coghill,1 Tobias Banaschewski,2 Michel Lecendreux,3 César Soutullo,4 Alessandro Zuddas,5 Ben Adeyi,6 Shaw Sorooshian7 1Division of Neuroscience, University of Dundee, Dundee, UK; 2Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; 3Paediatric Sleep Centre and National Reference Centre for Orphan Diseases: Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Robert-Debré University Hospital, Paris, France; 4Child and Adolescent Psychiatry Unit, Department of Psychiatry and Medical Psychology, University of Navarra Clinic, Pamplona, Spain; 5Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy; 6Shire, Wayne, PA, USA; 7Shire, Eysins, Switzerland Background: Following the approval of lisdexamfetamine dimesylate (LDX in several European countries for the treatment of attention-deficit/hyperactivity disorder (ADHD in children and adolescents with an inadequate response to methylphenidate (MPH treatment, the aim of the present analysis was to establish the response to LDX in subgroups of patients with different ADHD medication histories. Methods: This was a post hoc subgroup analysis of data from a 7-week, European, double-blind, dose-optimized, Phase III study. Patients aged 6–17 years were randomized 1:1:1 to LDX, placebo, or osmotic-release oral system methylphenidate (OROS-MPH. OROS-MPH was included as a reference arm rather than as a direct comparator. Efficacy was assessed in patients categorized according to their ADHD medication history using the ADHD Rating Scale IV and Clinical Global Impressions-Improvement (CGI-I scores. Results: The difference between active drug and placebo in least-squares mean change from baseline to endpoint in ADHD Rating Scale IV total score (95% confidence interval was similar between the overall study population (n

  1. Lisdexamfetamine dimesylate for the treatment of attention deficit hyperactivity disorder in adults with a history of depression or history of substance use disorder.

    Science.gov (United States)

    Kollins, Scott H; Youcha, Sharon; Lasser, Robert; Thase, Michael E

    2011-02-01

    To evaluate the efficacy and safety of lisdexamfetamine dimesylate in participants with attention deficit hyperactivity disorder and a history of depression and/or substance use disorder. History of these comorbidities was recorded from medical history forms completed by the study clinicians. An exploratory, post-hoc analysis was conducted using data from a randomized, double-blind, placebo-controlled, forced-dose titration study of lisdexamfetamine dimesylate. Adults with attention deficit hyperactivity disorder. Changes in Attention Deficit Hyperactivity Disorder Rating Scale IV total scores and Clinical Global Impressions-Improvement scale were used to evaluate the efficacy of lisdexamfetamine dimesylate. The incidence of treatment-emergent adverse events was also evaluated. The intention-to-treat population included 36 participants with a history of depression and 17 participants with a history of substance use disorder. Mean changes in Attention Deficit Hyperactivity Disorder Rating Scale IV and Clinical Global Impressions-Improvement from baseline to endpoint for these subpopulations were similar to those of participants without a history of depression and/or history of substance use disorder. Lisdexamfetamine dimesylate was generally well tolerated in all subgroups. The response to lisdexamfetamine dimesylate and the treatment-emergent adverse event profiles of participants with a history of depression and/or a history of substance use disorder were similar to those of participants with no history of these disorders. Larger studies that prospectively enroll participants with attention deficit hyperactivity disorder and these comorbid disorders are needed to more conclusively evaluate the safety and efficacy of stimulant treatment in these populations.

  2. Health-related quality of life and functional outcomes from a randomized-withdrawal study of long-term lisdexamfetamine dimesylate treatment in children and adolescents with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Banaschewski, Tobias; Johnson, Mats; Lecendreux, Michel; Zuddas, Alessandro; Adeyi, Ben; Hodgkins, Paul; Squires, Liza A; Coghill, David R

    2014-12-01

    The stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well tolerated treatment for the symptoms of attention-deficit/hyperactivity disorder (ADHD). Positive impacts of LDX on health-related quality of life and functional impairment have previously been demonstrated in a 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in Europe. Maintenance of these broad benefits, as well as symptomatic control, is a key goal of long-term management of ADHD. Secondary objectives of this multinational study in children and adolescents with ADHD were to assess the long-term maintenance of effectiveness of LDX in improving health-related quality of life and reducing functional impairment, as gauged using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE: PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively. Patients aged 6-17 years with diagnosed ADHD and a baseline ADHD Rating Scale IV total score of at least 28 were enrolled from the previous European study and from US sites. Patients who completed an open-label LDX treatment period of at least 26 weeks were randomized (1:1) to continue on their optimized dose of LDX or to switch to placebo for a 6-week, double-blind, withdrawal period. Parents completed CHIP-CE: PRF and WFIRS-P questionnaires at weeks 0, 8 and 26 of the open-label period and at weeks 0 and 6 of the randomized-withdrawal period, or at early termination. The endpoint of each period was defined as the last visit with valid data. Effect sizes were the difference (LDX minus placebo) in least-squares (LS)-mean change from baseline to endpoint divided by root-mean-square error. P values were nominal and not adjusted for multiple comparisons. The open-label and randomized full analysis sets comprised 262 and 153 (LDX n = 76; placebo n = 77) patients, respectively. Mean pretreatment CHIP-CE: PRF T-scores were more than one

  3. Lisdexamfetamine: A pharmacokinetic review.

    Science.gov (United States)

    Comiran, Eloisa; Kessler, Félix Henrique; Fröehlich, Pedro Eduardo; Limberger, Renata Pereira

    2016-06-30

    Lisdexamfetamine (LDX) is a d-amphetamine (d-AMPH) pro-drug used to treat Attention Deficit and Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED) symptoms. The in vivo pharmacodynamics of LDX is the same as that of its active product d-AMPH, although there are a few qualitative and quantitative differences due to pharmacokinetics. Due to the specific pharmacokinetics of the long-acting stimulants, this article revises the pharmacokinetic studies on LDX, the newest amphetamine pro-drug. The Medline/Pubmed, Science Direct and Biblioteca Virtual em Saúde (Lilacs and Ibecs) (2007-2016) databases were searched for articles and their list of references. As for basic pharmacokinetics studies, since LDX is a newly developed medication, there are few results concerning biotransformation, distribution and the use of different biological matrices for analysis. This is the first robust review on this topic, gathering data from all clinical pharmacokinetics studies available in the literature. The particular pharmacokinetics of LDX plays a major role in studying this pro-drug, since this knowledge was essential to understand some reports on clinical effects in literature, e.g. the small likelihood of reducing the effect by interactions, the effect of long duration use and the still questionable reduction of the potential for abuse. In general the already well-known pharmacokinetic properties of amphetamine make LDX relatively predictable, simplifying the use of LDX in clinical practice. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Update on optimal use of lisdexamfetamine in the treatment of ADHD

    Directory of Open Access Journals (Sweden)

    Madaan V

    2013-07-01

    Full Text Available Vishal Madaan, Venkata Kolli, Durga P Bestha, Manan J ShahDepartment of Psychiatry and Neurobehavioral Sciences, Division of Child and Family Psychiatry, University of Virginia Health System, Charlottesville, VA, USAAbstract: Lisdexamfetamine (LDX has been a recent addition to the treatment armamentarium for Attention Deficit Hyperactivity Disorder (ADHD. It is unique among stimulants as it is a prodrug, and has been found to be safe and well-tolerated medication in children older than 6 years, adolescents and adults. It has a smooth onset of action, exerts its action up to 13 hours and may have less rebound symptoms. LDX has proven to be effective in the treatment of ADHD in placebo controlled trials, and improved performance in simulated academic and work environments have been noticed. Both stimulant naïve and stimulant-exposed patients with ADHD appear to benefit from LDX. It has also shown some promise in improving emotional expression and executive function of patients with ADHD. Adverse effects such as decrease in sleep, loss of appetite and others have been reported with LDX use, just as with other stimulant formulations. Since most such studies exclude subjects with preexisting cardiac morbidity, prescribing precautions should be taken with LDX in such subjects, as with any other stimulant. Study subjects on LDX have been reported to have low scores on drug likability scales, even with intravenous use; as a result, LDX may have somewhat less potential for abuse and diversion. There is a need for future studies comparing other long acting stimulants with LDX in ADHD; in fact clinical trials comparing LDX with OROS (osmotic controlled-release oral delivery system methylphenidate are currently underway. Furthermore, the utility of this medication in other psychiatric disorders and beyond ADHD is being investigated.Keywords: lisdexamfetamine, ADHD, functional impairment, pharmacotherapy

  5. Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder

    Science.gov (United States)

    McElroy, Susan L.; Ferreira-Cornwell, M. Celeste; Radewonuk, Jana; Gasior, Maria

    2017-01-01

    Importance The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important. Objective To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder. Design, Setting, and Participants A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions−Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase. Interventions Lisdexamfetamine administration. Main Outcomes and Measures The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events. Results Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136

  6. Campaign for Levitation in LDX

    Science.gov (United States)

    Garnier, D. T.; Hansen, A. K.; Mauel, M. E.; Ortiz, E. E.; Boxer, A. C.; Ellsworth, J. L.; Karim, I.; Kesner, J.; Michael, P. C.; Zhukovsky, A.

    2006-10-01

    In the past year, preparations have been made for the first flight of the Levitated Dipole Experiment (LDX). LDX, which consists of a 560 kg superconducting coil floating within a 5 m diameter vacuum chamber, is designed to study fusion relevant plasmas confined in a dipole magnetic field. During the spring, a high temperature superconducting levitation coil was integrated into the LDX facility. Testing was undertaken to verify the thermal performance of the coil under expected levitation conditions. In addition, a real-time operating system digital control system was developed that will be used for the levitation control. In July, plasma experiments were conducted with all superconducting magnets in operation. While still supported, roughly 75% of the weight of the floating coil was magnetically lifted by the levitation coil above. A series of plasma experiments were conducted with the same magnetic geometry as will be the case during levitation. During August, the second generation launcher system will be installed. The launcher, which retracts beyond the plasma's last closed field lines during operation, is designed to safely catch the floating coil following an unexpected loss of control. After this installation, levitation experiments will commence.

  7. Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial.

    Science.gov (United States)

    Hudson, James I; McElroy, Susan L; Ferreira-Cornwell, M Celeste; Radewonuk, Jana; Gasior, Maria

    2017-09-01

    The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important. To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder. A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions-Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase. Lisdexamfetamine administration. The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events. Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131) for placebo. Lisdexamfetamine demonstrated superiority over

  8. Lisdexamfetamine: chemistry, pharmacodynamics, pharmacokinetics, and clinical efficacy, safety, and tolerability in the treatment of binge eating disorder.

    Science.gov (United States)

    Ward, Kristen; Citrome, Leslie

    2018-02-01

    The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing. D-amphetamine acts primarily to increase the concentrations of synaptic dopamine and norepinephrine. Metabolism of LDX to d-amphetamine occurs when peptidases in red blood cells cleave the covalent bond between d-amphetamine and l-lysine. D-amphetamine is then further metabolized by CYP2D6. Excretion is primarily through renal mechanisms. In clinical trials, LDX demonstrated statistical and clinical superiority over placebo in reducing binge eating days per week at doses of 50 and 70 mg daily. Commonly reported side effects of LDX include dry mouth, insomnia, weight loss, and headache, and its use should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia or coronary artery disease. As with all CNS stimulants, risk of abuse needs to be assessed prior to prescribing.

  9. Novel pharmacologic treatment in acute binge eating disorder – role of lisdexamfetamine

    Directory of Open Access Journals (Sweden)

    Guerdjikova AI

    2016-04-01

    Full Text Available Anna I Guerdjikova,1,2 Nicole Mori,1,2 Leah S Casuto,1,2 Susan L McElroy1,2 1Lindner Center of HOPE, Mason, OH, USA; 2Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA Abstract: Binge eating disorder (BED is the most common eating disorder and an important public health problem. It is characterized by recurrent episodes of excessive food consumption accompanied by a sense of loss of control over the binge eating behavior without the inappropriate compensatory weight loss behaviors of bulimia nervosa. BED affects both sexes and all age groups and is associated with medical and psychiatric comorbidities. Until recently, self-help and psychotherapy were the primary treatment options for patients with BED. In early 2015, lisdexamfetamine dimesylate, a prodrug stimulant marketed for attention deficit hyperactive disorder, was the first pharmacologic agent to be approved by the US Food and Drug Administration for the treatment of moderate or severe BED in adults. This article summarizes BED clinical presentation, and discusses the pharmacokinetic profile, efficacy, and safety of lisdexamfetamine dimesylate in the treatment of BED in adults. Keywords: binging, overeating, Vyvanse, stimulant, approved medication

  10. Predicted effect size of lisdexamfetamine treatment of attention deficit/hyperactivity disorder (ADHD) in European adults: Estimates based on indirect analysis using a systematic review and meta-regression analysis.

    Science.gov (United States)

    Fridman, M; Hodgkins, P S; Kahle, J S; Erder, M H

    2015-06-01

    There are few approved therapies for adults with attention-deficit/hyperactivity disorder (ADHD) in Europe. Lisdexamfetamine (LDX) is an effective treatment for ADHD; however, no clinical trials examining the efficacy of LDX specifically in European adults have been conducted. Therefore, to estimate the efficacy of LDX in European adults we performed a meta-regression of existing clinical data. A systematic review identified US- and Europe-based randomized efficacy trials of LDX, atomoxetine (ATX), or osmotic-release oral system methylphenidate (OROS-MPH) in children/adolescents and adults. A meta-regression model was then fitted to the published/calculated effect sizes (Cohen's d) using medication, geographical location, and age group as predictors. The LDX effect size in European adults was extrapolated from the fitted model. Sensitivity analyses performed included using adult-only studies and adding studies with placebo designs other than a standard pill-placebo design. Twenty-two of 2832 identified articles met inclusion criteria. The model-estimated effect size of LDX for European adults was 1.070 (95% confidence interval: 0.738, 1.401), larger than the 0.8 threshold for large effect sizes. The overall model fit was adequate (80%) and stable in the sensitivity analyses. This model predicts that LDX may have a large treatment effect size in European adults with ADHD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. New and extended-action treatments in the management of ADHD: a critical appraisal of lisdexamfetamine in adults and children

    Directory of Open Access Journals (Sweden)

    Diana Domnitei

    2010-05-01

    Full Text Available Diana Domnitei, Vishal MadaanDepartment of Psychiatry, Creighton University Medical Center, Omaha, NE, USAAbstract: Treatment guidelines from the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics state that stimulant medications have the most evidence for safety and efficacy in the treatment of childhood attention deficit hyperactivity disorder (ADHD. Longer-acting stimulants are thus considered as first-line for management of ADHD symptoms. Over the years, concerns about the abuse potential of stimulants have led to the development of alternative formulations of these agents. One such recent development, lisdexamfetamine (LDX was FDA approved for treating ADHD in children in early 2007 and in adults in early 2008. LDX is a prodrug, which when orally ingested, is converted to l-lysine and active d-amphetamine, which is responsible for its therapeutic activity. This unique formulation may lead to a possible reduction of the abuse potential, by bypassing the first-pass metabolism. In fact, a statistically significant difference for the ‘liking’ effects on the Drug Questionnaire Response has been reported with intravenous LDX compared to d-amphetamine. LDX appears to have an efficacy and tolerability profile comparable to other extended-release stimulant formulations used to treat ADHD, but reduced potential for abuse-related liking effects when compared to equivalent amounts of immediate-release d-amphetamine. The most common adverse events include decreased appetite, insomnia, upper abdominal pain, headache, irritability, weight loss, and nausea.Keywords: lisdexamfetamine, attention deficit hyperactivity disorder, adults, children

  12. Safety and Tolerability of Lisdexamfetamine

    DEFF Research Database (Denmark)

    Hansen, Melissa Voigt; Darling, Lise; Holst, Helle

    2015-01-01

    BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder in children. Pharmacotherapy plays a main role in multimodal treatment, albeit adverse effects are a concern. Lisdexamfetamine is a newer pharmacological option and post-marketing studies on adverse ...

  13. Lisdexamfetamine

    Science.gov (United States)

    ... one else can take it accidentally or on purpose. Keep track of how many capsules are left ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  14. Comparison of therapy augmentation and deviation rates from the recommended once-daily dosing regimen between LDX and commonly prescribed long-acting stimulants for the treatment of ADHD in youth and adults.

    Science.gov (United States)

    Setyawan, Juliana; Hodgkins, Paul; Guérin, Annie; Gauthier, Geneviève; Cloutier, Martin; Wu, Eric; Erder, M Haim

    2013-10-01

    To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants. ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large U.S. administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models. Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28-3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73-4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically

  15. Lisdexamfetamine for treatment of attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Cowles, Brian J

    2009-04-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of the prodrug lisdexamfetamine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults and describe its potential place in therapy. Primary literature published between January 1, 1990, and August 1, 2008, was selected from PubMed using the search key words lisdexamfetamine, Vyvanse, and NRP104. References of selected publications were also reviewed. Posters and abstracts of research presented at national meetings were reviewed when available. The product labeling for Vyvanse was also used. Preference was given to published, randomized, and controlled research describing the pharmacokinetics, efficacy, and safety of lisdexamfetamine. Noncontrolled studies, postmarketing reports, and poster presentations were considered secondly. All published studies were included. Lisdexamfetamine is a prodrug of dextroamphetamine covalently bound to l-lysine, which is activated during first-pass metabolism. The unique pharmacokinetic profile owing to lisdexamfetamine's prodrug design and rate-limited enzymatic biotransformation allows for once-daily dosing with a duration of activity of approximately 12 hours. Lisdexamfetamine has been proven to reduce the symptoms of ADHD both in children aged 6-12 years and adults aged 18-55 years, decreasing ADHD rating scale scores by approximately 27 and 19 points, respectively. Adverse effects with an incidence greater than 10% during preclinical trials included appetite suppression, insomnia, and headache. Lisdexamfetamine's unique pharmacokinetic properties may provide additional safety with regard to reducing abuse potential. As with other central nervous system (CNS) stimulants, concerns regarding sudden cardiac death and adverse effects on growth also apply to lisdexamfetamine. Lisdexamfetamine provides another amphetamine-based CNS stimulant option for treatment of children and adults with ADHD. However, its use may be limited by a

  16. Performance of the Conduction-Cooled LDX Levitation Coil

    Science.gov (United States)

    Michael, P. C.; Schultz, J. H.; Smith, B. A.; Titus, P. H.; Radovinsky, A.; Zhukovsky, A.; Hwang, K. P.; Naumovich, G. J.; Camille, R. J.

    2004-06-01

    The Levitated Dipole Experiment (LDX) was developed to study plasma confinement in a dipole magnetic field. Plasma is confined in the magnetic field of a 680-kg Nb3Sn Floating Coil (F-coil) that is electromagnetically supported at the center of a 5-m diameter by 3-m tall vacuum chamber. The Levitation Coil (L-coil) is a 2800-turn, double pancake winding that supports the weight of the F-coil and controls its vertical position within the vacuum chamber. The use of high-temperature superconductor (HTS) Bi-2223 for the L-coil minimizes the electrical and cooling power needed for levitation. The L-coil winding pack and support plate are suspended within the L-coil cryostat and cooled by conduction to a single-stage cryocooler rated for 25-W heat load at approximately 20 K. The coil current leads consist of conduction-cooled copper running from room temperature to 80 K and a pair of commercially-available, 150-A HTS leads. An automatically filled liquid-nitrogen reservoir provides cooling for the coil's radiation shield and for the leads' 80-K heat stations. This paper discusses the L-coil system design and its observed cryogenic performance.

  17. Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Patrick C. Dolder

    2017-09-01

    Full Text Available Rationale: Lisdexamfetamine is a prodrug of D-amphetamine used for the treatment of attention-deficit/hyperactivity disorder (ADHD. Lisdexamfetamine is thought to have a prolonged pharmacokinetic profile compared with oral D-amphetamine, possibly associated with lower drug liking and a lower risk of oral misuse. However, differences in the pharmacokinetics and pharmacodynamics of lisdexamfetamine and D-amphetamine have not been directly compared.Methods: Equimolar doses of D-amphetamine (40 mg and lisdexamfetamine (100 mg, and placebo were administered in 24 healthy subjects in a randomized, double-blind, placebo-controlled, cross-over study. Plasma concentrations of amphetamine, subjective effects, and vital signs were repeatedly assessed. The pharmacokinetic parameters were determined using compartmental modeling.Results: The increase in plasma concentrations of amphetamine had a 0.6 ± 0.6 h (mean ± SD longer lag time and reached peak levels 1.1 ± 1.5 h later after lisdexamfetamine administration compared with D-amphetamine administration, but no differences in maximal concentrations or total exposure (AUC were found between the two treatments. Consistent with the pharmacokinetics, the subjective and cardiovascular stimulant effects of lisdexamfetamine also occurred later compared with D-amphetamine. However, no differences in peak ratings of potentially abuse-related subjective drug effects (e.g., drug liking, drug high, stimulation, happy, well-being, and self-confidence were observed after lisdexamfetamine administration compared with D-amphetamine administration. Lisdexamfetamine and D-amphetamine also produced similar peak increases in mean arterial blood pressure, heart rate, body temperature, pupil size, and adverse effects.Conclusion: The pharmacokinetics and pharmacodynamics of lisdexamfetamine are similar to D-amphetamine administered 1h later. Lisdexamfetamine is likely associated with a similar risk of oral abuse as D

  18. Short fatigue cracks nucleation and growth in lean duplex stainless steel LDX 2101

    Energy Technology Data Exchange (ETDEWEB)

    Strubbia, R., E-mail: strubbia@ifir-conicet.gov.ar [Instituto de Física Rosario – CONICET, Universidad Nacional de Rosario (Argentina); Hereñú, S.; Alvarez-Armas, I. [Instituto de Física Rosario – CONICET, Universidad Nacional de Rosario (Argentina); Krupp, U. [Faculty of Engineering and Computer Science, University of Applied Sciences Osnabrück (Germany)

    2014-10-06

    This work is focused on the fatigue damage of lean duplex stainless steels (LDSSs) LDX 2101. Special interest is placed on analyzing short fatigue crack behavior. In this sense, short crack initiation and growth during low cycle fatigue (LCF) and short crack nucleation during high cycle fatigue (HCF) of this LDSS have been studied. The active slip systems and their associated Schmid factors (SF) are determined using electron backscattered diffraction (EBSD). Additionally, the dislocation structure developed during cycling is observed by transmission electron microscopy (TEM). Regardless of the fatigue regime, LCF and HCF, short cracks nucleate along intrusion/extrusions in ferritic grains. Moreover, during the LCF phase boundaries decelerate short crack propagation. These results are rationalized by the hardness of the constitutive phases and the dependence of screw dislocation mobility in the ferrite phase on strain rate and stress amplitude.

  19. Cell therapy in the treatment of bipolar mania in an animal model: a proof of concept study

    Directory of Open Access Journals (Sweden)

    Bruna M. Ascoli

    2017-05-01

    Full Text Available Abstract Introduction The rationale of mesenchymal stem cells (MSCs as a novel therapeutic approach in certain neurodegenerative diseases is based on their ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar disorder (BD in preclinical, imaging and postmortem studies. Therefore, the development of new strategies to stimulate the neurogenesis process in BD is crucial. Objectives To investigate the behavioral and neurochemical changes induced by transplantation of MSCs in a model of mania-like behavior induced by lisdexamfetamine dimesylate (LDX. Methods Wistar rats (n=65 received one oral daily dose of LDX (10 mg/kg or saline for 14 days. On the 8th day of treatment, the animals additionally received intrahippocampal saline or MSC (1 µL containing 25,000 cells or lithium (47.5 mg/kg as an internal experimental control. Two hours after the last administration, behavioral and neurochemical analyses were performed. Results LDX-treated rats had increased locomotor activity compared to saline-saline rats (p=0.004, and lithium reversed LDX-related hyperactive behavior (p0.05 in the hippocampus of rats. Conclusion Even though these results suggest that a single intrahippocampal injection of MSCs was not helpful to treat hyperactivity induced by LDX and neither influenced BDNF secretion, we cannot rule out the possible therapeutic effects of MSCs. Further research is required to determine direct effects of LDX on brain structures as well as in other pathophysiological targets related to BD.

  20. Evaluation of the Duration of Action and Comparative Effectiveness of Lisdexamfetamine Dimesylate and Behavioral Treatment in Youth With ADHD in a Quasi-Naturalistic Setting.

    Science.gov (United States)

    Manos, Michael J; Caserta, Donald A; Short, Elizabeth J; Raleigh, Kristina L; Giuliano, Kimberly C; Pucci, Nicole C; Frazier, Thomas W

    2015-07-01

    This study compared the relative effects of three treatment conditions: long-acting stimulant medication (MED), behavior modification, and medication/behavioral treatments combined (COM) in children with ADHD. A total of 25 children, aged 6 to 12 years, received the three treatment conditions during a 7-week Summer Treatment Program in an alternating treatments design. Counselors completed behavioral ratings from 0.5 to 12.5 hr post dose, and parents completed nighttime ratings. Ratings for SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) and for following instructions indicated COM and MED improved symptoms over BEH treatment beginning 3 hr post dose (p = .008), with ratings maintained 12.5 hr post dose (p = .001 and .006). Results for frustration tolerance indicated significant improvement in all three conditions until 9 hr post dose. MED and COM separated from BEH at 3 hr post dose, and sustained benefit was observed across the day for two of three measures. BEH appears to have an additive effect, extending the duration of frustration tolerance. © 2012 SAGE Publications.

  1. Weldability aspects of a newly developed duplex stainless steel LDX 2101

    Energy Technology Data Exchange (ETDEWEB)

    Westin, E.M. [Avesta Research Centre, Avesta (Sweden). Outokumpu Stainless; Brolund, B. [SSAB Tunnplat, Borlaenge (Sweden); Hertzman, S. [Outokumpu Stainless Research Foundation, Stockholm (Sweden)

    2008-06-15

    Duplex grades have, due to balanced chemical compositions of both filler and base metals, a weldability that allows for successful welding using a majority of the technically relevant techniques of today. In order to fulfil the performance requirements several aspects must be considered. In the heat affected zone (HAZ) the austenite reformation must be reasonably high and in the weld metal the microstructure must be stable so that e.g. high productivity welding and multi-pass welding are possible, without precipitation of detrimental phases in previous passes. This paper addresses the effect of alloying elements and thermal cycles on phase balance in the high temperature HAZ (HTHAZ) of the newly developed lean duplex grade LDX 2101 (EN 1.4162, UNS S32101). Bead-on-plate welds and simulated weld structures have been produced and investigated using metallography, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results are analysed using the thermodynamic database Thermo-Calc and a model for phase transformation based on a paraequilibrium assumption for ferrite-austenite transformation. In the temperature region outside the paraequilibrium domain, growth controlled by diffusion of substitutional elements was considered. The analysis follows a model by Cahn regarding grain boundary nucleated growth and the Hillert-Engberg model on kinetics of spherical and planar growth. (orig.)

  2. DESIGN, FABRICATION AND TEST OF THE REACT AND WIND, NB(3)SN, LDX FLOATING COIL CONDUCTOR

    International Nuclear Information System (INIS)

    SMITH, B.A.; MICHAEL, P.C.; MINERVINI, J.V.; TAKAYASU, M.; SCHULTZ, J.H.; GREGORY, E.; PYON, T.; SAMPSON, W.B.; GHOSH, A.; SCANLAN, R.

    2000-01-01

    The Levitated Dipole Experiment (LDX) is a novel approach for studying magnetic confinement of a fusion plasma. In this approach, a superconducting ring coil is magnetically levitated for up to 8 hours a day in the center of a 5 meter diameter vacuum vessel. The levitated coil, with on-board helium supply, is called the gloating Coil (F-Coil). Although the maximum field at the coil is only 5.3 tesla, a react-and-wind Nb 3 Sn conductor was selected because the relatively high critical temperature will enable the coil to remain levitated while it warms from 5 K to 10 K. Since pre-reacted Nb 3 Sn tape is no longer commercially available, a composite conductor was designed that contains an 18 strand Nb 3 Sn Rutherford cable. The cable was reacted and then soldered into a structural copper channel that completes the conductor and also provides quench protection. The strain state of the cable was continuously controlled during fabrication steps such as: soldering into the copper channel, spooling, and coil winding, to prevent degradation of the critical current. Measurements of strand and cable critical currents are reported, as well as estimates of the effect of fabrication, winding and operating strains on critical current

  3. Effect of aging time on intergranular corrosion behavior of a newly developed LDX 2404 lean duplex stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hui [School of Materials Engineering, Shanghai University of Engineering Science, Shanghai 201620 (China); Zhang, Ziying, E-mail: zzying@sues.edu.cn [School of Materials Engineering, Shanghai University of Engineering Science, Shanghai 201620 (China); Zhang, Huizhen [School of Management, University of Shanghai for Science and Technology, Shanghai 200093 (China); Hu, Jun [School of Materials Engineering, Shanghai University of Engineering Science, Shanghai 201620 (China); Li, Jin [Department of Materials Science, Fudan University, Shanghai 200433 (China)

    2016-07-05

    The effect of aging at 700 °C for various times on the intergranular corrosion behavior of LDX 2404 duplex stainless steel is investigated by morphological observation and electrochemical detection. Scanning electronic microscopy and transmission electronic microscopy analysis reveal that Cr{sub 2}N, M{sub 23}C{sub 6} and the sigma and chi phases nucleate simultaneously at the initial stages of aging. The granular particles of sigma phase grow larger but fewer with the increase of aging time. The electrochemical detection results show that intergranular corrosion become more severe and the corrosion type evolves from intergranular corrosion into general corrosion as the holding time extends to 48 h. - Highlights: • The IGC behavior of aged LDX 2404 is investigated. • Cr{sub 2}N, M{sub 23}C{sub 6} and the σ and χ phases nucleate simultaneously at the initial stages of aging. • IGC resistance decreases with the increase of aging time. • The corrosion type evolves from IGC into general corrosion for longer aging times.

  4. Dgroup: DG00973 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG00973 Chemical ... DGroup Lisdexamfetamine ... D08130 ... Lisdexamfetamine (INN) D04747 ... Lisdexamfe...tamine dimesylate (USAN); Lisdexamfetamine mesilate (JAN) ... Neuropsychiatric agent ... DG01970 ... Age...nts for ADHD ATC code: N06BA12 Psychostimulant, Central sympathomimetic agent Active form of prodrug: Dextroamphetamine (Dexamfe

  5. Udvikling af cerebrale infarkter hos en 17-årig mand i behandling med sertralin og lisdexamfetamin

    DEFF Research Database (Denmark)

    Martinussen, Malene; Debes, Nanette Mol; Christensen, Catrine

    2016-01-01

    A 17-year-old male with ADHD who was treated with sertraline and lisdexamfetamine presented with transient episodes of speech impairment and right-sided hemiparesis preceded by headaches. Magnetic resonance imaging revealed three cerebral ischaemic lesions. Treatment was initiated with aspirin an...

  6. Udvikling af cerebrale infarkter hos en 17-årig mand i behandling med sertralin og lisdexamfetamin

    DEFF Research Database (Denmark)

    Martinussen, Malene; Debes, Nanette Mol; Christensen, Catrine

    2017-01-01

    A 17-year-old male with ADHD who was treated with sertraline and lisdexamfetamine presented with transient episodes of speech impairment and right-sided hemiparesis preceded by headaches. Magnetic resonance imaging revealed three cerebral ischaemic lesions. Treatment was initiated with aspirin an...

  7. Pharmacological Treatment of Binge Eating Disorder: Update Review and Synthesis

    Science.gov (United States)

    Reas, Deborah L.; Grilo, Carlos M.

    2015-01-01

    Introduction Binge-eating disorder (BED), a formal eating-disorder diagnosis in the DSM-5, is characterized by recurrent binge-eating, marked distress about binge-eating, and the absence of extreme weight compensatory behaviors. BED is more prevalent than other eating-disorders, with broader distribution across age, sex, and ethnic/racial groups, and is associated strongly with obesity and heightened risk for psychiatric/medical comorbidities. Areas Covered This article provides an overview of pharmacotherapy for BED with a focus on III randomized controlled trials (RCTs). The search with minimal methodological inclusion requirements yielded 22 RCTs investigating several different medication classes; most were pharmacotherapy-only trials with eight trials testing combination approaches with psychological-behavioral methods. Expert Opinion The evidence base regarding pharmacotherapy for BED remains limited, although this year the FDA approved the first medication (i.e., lisdexamfetamine dimesylate; LDX) specifically for moderate-to-severe BED. Data from RCTs suggests certain medications are superior to placebo for reducing binge-eating over the short-term; almost no data exist regarding longer-term effects of pharmacotherapy for BED. Except for topiramate, which significantly reduces both binge-eating and weight, tested medications yield minimal weight loss and LDX is not indicated for weight loss. Psychological-behavioral and combination approaches with certain medications yield superior outcomes to pharmacotherapy-only acutely and over longer-term follow-up. PMID:26044518

  8. Phase synchronization of oxygenation waves in the frontal areas of children with attention-deficit hyperactivity disorder detected by optical diffusion spectroscopy correlates with medication

    Science.gov (United States)

    Wigal, Sharon B.; Polzonetti, Chiara M.; Stehli, Annamarie; Gratton, Enrico

    2012-12-01

    The beneficial effects of pharmacotherapy on children with attention-deficit hyperactivity disorder (ADHD) are well documented. We use near-infrared spectroscopy (NIRS) methodology to determine reorganization of brain neurovascular properties following the medication treatment. Twenty-six children with ADHD (ages six through 12) participated in a modified laboratory school protocol to monitor treatment response with lisdexamfetamine dimesylate (LDX; Vyvanse, Shire US Inc.). All children refrained from taking medication for at least two weeks (washout period). To detect neurovascular reorganization, we measured changes in synchronization of oxy (HbO2) and deoxy (HHb) hemoglobin waves between the two frontal lobes. Participants without medication displayed average baseline HbO2 phase difference at about -7-deg. and HHb differences at about 240-deg.. This phase synchronization index changed after pharmacological intervention. Medication induced an average phase changes of HbO2 after first medication to 280-deg. and after medication optimization to 242-deg.. Instead first medication changed of the average HHb phase difference at 186-deg. and then after medication optimization to 120-deg. In agreement with findings of White et al., and Varela et al., we associated the phase synchronization differences of brain hemodynamics in children with ADHD with lobe specific hemodynamic reorganization of HbO2- and HHB oscillations following medication status.

  9. Lisdexamfetamine in the treatment of moderate-to-severe binge eating disorder in adults: systematic review and exploratory meta-analysis of publicly available placebo-controlled, randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Fornaro M

    2016-07-01

    Full Text Available Michele Fornaro,1,2 Marco Solmi,3–5 Giampaolo Perna,2,6 Domenico De Berardis,2,7 Nicola Veronese,5,8 Laura Orsolini,2,9 Licinia Ganança,1,10 Brendon Stubbs11,12 1New York State Psychiatric Institute, Columbia University, New York City, NY, USA; 2Polyedra Research Group®, Ascoli, 3Department of Neurosciences, University of Padua, 4Department of Mental Health, National Health Service, Padova, 5IREM Institute for Clinical Research and Education in Medicine, Padova, 6Department of Clinical Neurosciences, Hermanas Hospitalarias – Villa San Benedetto Menni Hospital, FoRiPsi, Albese con Cassano, Como, 7Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, National Health Service, Hospital “G Mazzini”, Teramo, 8Department of Medicine (DIMED, University of Padua, Padova, Italy; 9Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, UK; 10Department of Psychiatry, School of Medicine, University of Lisbon, Lisbon, Portugal; 11Department of Health Service and Population Research, Institute of Psychiatry, King’s College London, 12Department of Physiotherapy, South London and Maudsley NHS Foundation Trust, London, UK Background: Preliminary placebo-controlled evidence paved the ground to the US Food and Drug Administration approval extension of lisdexamfetamine for the treatment of moderate-to-severe binge eating disorder (BED in adults.Objectives: To provide a preliminary qualitative and quantitative synthesis of the placebo-controlled, randomized clinical trials (RCTs considering the efficacy and tolerability of lisdexamfetamine in the acute and/or maintenance treatment of moderate-to-severe BED in adults.Methods: A preliminary, yet comprehensive, systematic review was performed by accessing a broad range of resources providing publicly available data about lisdexamfetamine at the time of inquiry (March 2016. Study

  10. Relationships between clinical scales and binge eating days in adults with moderate to severe binge eating disorder in two Phase III studies.

    Science.gov (United States)

    Citrome, Leslie; Kando, Judith C; Bliss, Caleb

    2018-01-01

    In two Phase III studies, lisdexamfetamine dimesylate (LDX) reduced binge eating (BE) days/week in adults with moderate to severe binge eating disorder (BED) and was associated with improvement based on the Clinical Global Impressions-Improvement (CGI-I) scale. In this study, post hoc analyses examined the relationships between clinical observations and clinical rating scales in individuals with BED. NCT01718483 (ClinicalTrials.gov/ct2/show/NCT01718483); NCT01718509 (ClinicalTrials.gov/ct2/show/NCT01718509). Two 12-week, double-blind, placebo-controlled studies randomized (1:1) adults meeting Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition, Text Revision, BED criteria and with protocol-defined moderate to severe BED (study 1, N=383; study 2, N=390) to placebo or dose-optimized LDX (50 or 70 mg). Assessments included the number of BE days/week, CGI-Severity (CGI-S) and CGI-I scores, and Yale-Brown Obsessive Compulsive Scale modified for Binge Eating (Y-BOCS-BE) total scores. For these post hoc analyses, data were pooled across studies and treatment arms. Statistical assessments included Spearman correlations and equipercentile linking analyses (ELA). Reported P -values are nominal (descriptive and not adjusted for multiplicity). At baseline, nominally significant correlations with CGI-S scores were reported for BE days/week ( r =0.374; P <0.0001) and Y-BOCS-BE total scores ( r =0.319; P <0.0001). Baseline ELA for CGI-S further characterized this relationship: a CGI-S score of 4 (moderately ill) corresponding to 3.504 BE days/week and a Y-BOCS-BE total score of 18.6. Nominally significant correlations with CGI-I scores were reported for changes from baseline at study endpoint for BE days/week ( r =0.647; P <0.0001) and Y-BOCS-BE total scores ( r =0.741; P <0.0001). ELA for CGI-I scores at study endpoint showed that a CGI-I score of 1 (very much improved) corresponds to a reduction from baseline of 4.504 BE days/week and 19.4 points for Y

  11. Pharmacokinetic variability of long-acting stimulants in the treatment of children and adults with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Ermer, James C; Adeyi, Ben A; Pucci, Michael L

    2010-12-01

    Methylphenidate- and amfetamine-based stimulants are first-line pharmacotherapies for attention-deficit hyperactivity disorder, a common neurobehavioural disorder in children and adults. A number of long-acting stimulant formulations have been developed with the aim of providing once-daily dosing, employing various means to extend duration of action, including a transdermal delivery system, an osmotic-release oral system, capsules with a mixture of immediate- and delayed-release beads, and prodrug technology. Coefficients of variance of pharmacokinetic measures can estimate the levels of pharmacokinetic variability based on the measurable variance between different individuals receiving the same dose of stimulant (interindividual variability) and within the same individual over multiple administrations (intraindividual variability). Differences in formulation clearly impact pharmacokinetic profiles. Many medications exhibit wide interindividual variability in clinical response. Stimulants with low levels of inter- and intraindividual variability may be better suited to provide consistent levels of medication to patients. The pharmacokinetic profile of stimulants using pH-dependent bead technology can vary depending on food consumption or concomitant administration of medications that alter gastric pH. While delivery of methylphenidate with the transdermal delivery system would be unaffected by gastrointestinal factors, intersubject variability is nonetheless substantial. Unlike the beaded formulations and, to some extent (when considering total exposure) the osmotic-release formulation, systemic exposure to amfetamine with the prodrug stimulant lisdexamfetamine dimesylate appears largely unaffected by such factors, likely owing to its dependence on systemic enzymatic cleavage of the precursor molecule, which occurs primarily in the blood involving red blood cells. The high capacity but as yet unidentified enzymatic system for conversion of lisdexamfetamine

  12. Cognitive remission: a novel objective for the treatment of major depression?

    Science.gov (United States)

    Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A; Maes, Michael; Fernandes, Brisa S; Berk, Michael; Carvalho, André F

    2016-01-22

    Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.

  13. Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants

    Directory of Open Access Journals (Sweden)

    Weyandt LL

    2014-09-01

    Full Text Available Lisa L Weyandt, Danielle R Oster, Marisa E Marraccini, Bergljot Gyda Gudmundsdottir, Bailey A Munro, Brynheld Martinez Zavras, Ben Kuhar Department of Psychology, University of Rhode Island, Kingston, RI, USA Abstract: Attention-deficit/hyperactivity disorder (ADHD is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity that cause functional impairment. Recent research indicates that symptoms persist into adulthood in the majority of cases, with prevalence estimates of approximately 5% in the school age population and 2.5%–4% in the adult population. Although students with ADHD are at greater risk for academic underachievement and psychosocial problems, increasing numbers of students with ADHD are graduating from high school and pursuing higher education. Stimulant medications are considered the first line of pharmacotherapy for individuals with ADHD, including college students. Although preliminary evidence indicates that prescription stimulants are safe and effective for college students with ADHD when used as prescribed, very few controlled studies have been conducted concerning the efficacy of prescription stimulants with college students. In addition, misuse of prescription stimulants has become a serious problem on college campuses across the US and has been recently documented in other countries as well. The purpose of the present systematic review was to investigate the efficacy of prescription stimulants for adolescents and young adults with ADHD and the nonmedical use and misuse of prescription stimulants. Results revealed that both prostimulant and stimulant medications, including lisdexamfetamine dimesylate, methylphenidate, amphetamines, and mixed-amphetamine salts, are effective at reducing ADHD symptoms in adolescents and adults with ADHD. Findings also suggest that individuals with ADHD may have higher rates of stimulant misuse than individuals without the disorder, and

  14. Is adjunctive pharmacotherapy in attention-deficit/hyperactivity disorder cost-effective in Canada: a cost-effectiveness assessment of guanfacine extended-release as an adjunctive therapy to a long-acting stimulant for the treatment of ADHD.

    Science.gov (United States)

    Lachaine, Jean; Sikirica, Vanja; Mathurin, Karine

    2016-01-16

    Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in children, with worldwide prevalence of ADHD varying from 5.9 to 7.1 %, depending on the reporter. In case of inadequate response to stimulants, combination therapy of stimulants and an adjunctive medication may improve the control of ADHD symptoms, reduce the dose-limiting adverse events, and help control comorbidities. To date, the only medication to be used for adjunctive therapy to psychostimulants is guanfacine extended release (GXR). The aim of this study was to assess the economic impact of GXR as an adjunct therapy with long-acting stimulants (GXR + stimulant) compared to long-acting stimulant monotherapy (stimulant alone) in the treatment of children and adolescents with ADHD in Canada. A Markov model was developed using health states defined based on the clinician-reported Clinical Global Impression-Severity (CGI-S) score (normal, mild, moderate, severe). Transition probabilities were calculated based on patient-level data from a published study. Long-acting stimulants available in Canada were considered in the base-case model: amphetamine mixed salts, methylphenidate HCl formulations, and lisdexamfetamine dimesylate. Analyses were conducted from a Canadian Ministry of Health (MoH; Ontario) and a societal perspective over a 1-year time horizon with weekly cycles. Over a 1-year time horizon, GXR + stimulant was associated with 0.655 quality-adjusted life year (QALY), compared to 0.627 QALY with stimulant alone, for a gain of 0.028 QALY. From a MoH perspective, GXR+ stimulant and stimulant alone were associated with total costs of $CA1,617 and $CA949, respectively (difference of $CA668), which resulted in an incremental cost-effectiveness ratio (ICER) of $CA23,720/QALY. From a societal perspective, GXR + stimulant and stimulant alone were associated with total costs of $CA3,915 and $CA3,582, respectively (difference of $CA334), which resulted in an ICER of $CA11

  15. 77 FR 47114 - Manufacturer of Controlled Substances; Notice of Application; AMRI Rensselaer, Inc.

    Science.gov (United States)

    2012-08-07

    ... Marihuana (7360) I Tetrahydrocannabinols (7370) I Amphetamine (1100) II Lisdexamfetamine (1205) II... (Marihuana), the company plans to bulk manufacture cannabidiol as a synthetic intermediate, which will be...

  16. Overview and Status of the Levitated Dipole Experiment

    Science.gov (United States)

    Garnier, D. T.; Hansen, A. K.; Mauel, M. E.; Ortiz, E.; Sunn-Pedersen, T.; Dagen, S.; Ellsworth, J.; Karim, I.; Kesner, J.; Minervini, J.; Michael, P.; Zhukovsky, A.

    2002-11-01

    The Levitated Dipole Experiment (LDX) is the first experiment designed to study high-β plasmas confined by a magnetic dipole with near classical energy confinement. The primary goal of the initial phase of LDX operation is the study of plasma behavior near marginal stability for interchange modes at high-β. Other areas of investigation include dipole confinement characteristics, the formation of convective cells within the closed field line geometry and the possibility of non-local transport. LDX consists of three superconducting magnets and highlights the role of innovative magnetic technology that makes possible explorations of entirely new confinement concepts. We describe the LDX machine design and detail the fabrication status of the superconducting floating-coil, charging-coil, and levitation-coil as LDX nears plasma operations. An overview of the project goals, overall program plan, and current status of the experiment will also be presented.

  17. 78 FR 59420 - Notice of Application for Special Permits

    Science.gov (United States)

    2013-09-26

    ... series cargo tanks except for the use of UNS S32101 (LDX 2101) as a material of construction and the head... of certain 172, 174.59 and empty packagings 174.61(a). containing residues of Class 1 smokeless...

  18. CONTRIBUTION OF LIVER NERVES, GLUCAGON, AND ADRENALINE TO THE GLYCEMIC RESPONSE TO EXERCISE IN RATS

    NARCIS (Netherlands)

    VAN DIJK, G; BALKAN, B; LINDFELDT, J; BOUWS, G; SCHEURINK, AJW; AHREN, B; STEFFENS, AB

    The contribution of hepatic sympathetic innervation, glucagon and adrenaline to the glycaemic response to exercise was investigated in rats. Hepatically denervated (LDX) or sham operated (SHAM) rats with permanent catheters were therefore submitted to swimming with or without infusion of

  19. Contribution of liver nerves, glucagon, and adrenaline to the glycaemic response to exercise in rats

    NARCIS (Netherlands)

    van Dijk, Gertjan; Balkan, B.; Lindfeldt, J.; Bouws, G.; Scheurink, A.J.W.; Ahrén, B.; Steffens, A.B.

    1994-01-01

    The contribution of hepatic sympathetic innervation, glucagon and adrenaline to the glycaemic response to exercise was investigated in rats. Hepatically denervated (LDX) or sham operated (SHAM) rats with permanent catheters were therefore submitted to swimming with or without infusion of

  20. Three-dimensional measurements of the lower extremity in children and adolescents using a low-dose biplanar X-ray device

    International Nuclear Information System (INIS)

    Gheno, Ramon; Nectoux, Eric; Herbaux, Bernard; Baldisserotto, Matteo; Glock, Luiz; Cotten, Anne; Boutry, Nathalie

    2012-01-01

    To evaluate three-dimensional (3D) measurements of the lower extremity using a biplanar low-dose X-ray device in children and adolescents. Firstly, 3D measurements of eight dried bones were analysed by a biplanar low-dose X-ray device (LDX) using stereoscopic software and compared with 3D computed tomography (CT). Secondly, 47 lower limbs of children and adolescents were studied using LDX two-dimensional (2D) and 3D measurements. Both parts were evaluated for femoral and tibial lengths and mechanical angles, frontal and lateral knee angulations, and the femoral neck-shaft angle. The 3D specimen comparison between LDX and CT measurements showed no significant differences: femoral length (P = 0.069), tibial length (P = 0.059), femoral mechanical angle (P = 0.475), tibial mechanical angle (P = 0.067), frontal knee angulation (P = 0.198), lateral knee angulation (P = 0.646) and femoral neck-shaft angle (P = 0.068). The comparison between LDX 2D and 3D measurements showed significant differences in tibial length (P = 0.003), femoral mechanical angle (P < 0.001) and femoral neck-shaft angle (P = 0.001); other parameters were unremarkable. The 3D LDX system presented reliable measurements compared with 3D CT. Differences between LDX 2D and 3D measurements were noted in the femoral mechanical angle, femoral neck-shaft angle and tibial length. Moderate to good interobserver agreement for the 3D LDX measurements were found. (orig.)

  1. [Efficacy of lisdexamphetamine to improve the behavioural and cognitive symptoms of attention deficit hyperactivity disorder: treatment monitored by means of the AULA Nesplora virtual reality test].

    Science.gov (United States)

    Diaz-Orueta, U; Fernandez-Fernandez, M A; Morillo-Rojas, M D; Climent, G

    2016-07-01

    Lisdexanfetamine (LDX) is the drug for attention deficit hyperactivity disorder (ADHD) undergoing the largest research volume in the latest years. However, no studies certify its usefulness for the improvement of cognitive functioning in ADHD. To evaluate the efficacy of LDX in the behavioral and cognitive improvement of a group of patients with ADHD. Such efficacy was measured by means of the administration of AULA Nesplora virtual reality test before the prescription of pharmacological treatment and right after the treatment with LDX. The sample comprised 85 patients between 6 and 16 years, with clinical diagnosis of ADHD, who attended treatment in a neuropediatrics consultation. All patients started pharmacological treatment with the proper dose of LDX after the clinical interview and the first administration of AULA test. After an average treatment of 7.5 months, AULA was administered again and the treatment progress based on cognitive and motor symptomatology was assessed. Results showed highly significant improvements in selective and sustained attention, quality of attention focus and hyperactivity; moderate improvements in impulsivity; and an incidence close to zero in processing speed. LDX constitutes an adequate treatment for the substantial improvement of attention and hyperactivity; such improvement can be monitored accurately by means of AULA virtual reality test.

  2. Influence of surface texture on the galling characteristics of lean duplex and austenitic stainless steels

    DEFF Research Database (Denmark)

    Wadman, Boel; Eriksen, J.; Olsson, M.

    2010-01-01

    Two simulative test methods were used to study galling in sheet forming of two types of stainless steel sheet: austenitic (EN 1.4301) and lean duplex LDX 2101 (EN 1.4162) in different surface conditions. The pin-on-disc test was used to analyse the galling resistance of different combinations of ...

  3. Binge-Eating Disorder in Adults

    Science.gov (United States)

    Brownley, Kimberly A.; Berkman, Nancy D.; Peat, Christine M.; Lohr, Kathleen N.; Cullen, Katherine E.; Bann, Carla M.; Bulik, Cynthia M.

    2017-01-01

    Background The best treatment options for binge-eating disorder are unclear. Purpose To summarize evidence about the benefits and harms of psychological and pharmacologic therapies for adults with binge-eating disorder. Data Sources English-language publications in EMBASE, the Cochrane Library, Academic OneFile, CINAHL, and ClinicalTrials.gov through 18 November 2015, and in MEDLINE through 12 May 2016. Study Selection 9 waitlist-controlled psychological trials and 25 placebo-controlled trials that evaluated pharmacologic (n = 19) or combination (n = 6) treatment. All were randomized trials with low or medium risk of bias. Data Extraction 2 reviewers independently extracted trial data, assessed risk of bias, and graded strength of evidence. Data Synthesis Therapist-led cognitive behavioral therapy, lisdexamfetamine, and second-generation antidepressants (SGAs) decreased binge-eating frequency and increased binge-eating abstinence (relative risk, 4.95 [95% CI, 3.06 to 8.00], 2.61 [CI, 2.04 to 3.33], and 1.67 [CI, 1.24 to 2.26], respectively). Lisdexamfetamine (mean difference [MD], −6.50 [CI, −8.82 to −4.18]) and SGAs (MD, −3.84 [CI, −6.55 to −1.13]) reduced binge-eating–related obsessions and compulsions, and SGAs reduced symptoms of depression (MD, −1.97 [CI, −3.67 to −0.28]). Headache, gastrointestinal upset, sleep disturbance, and sympathetic nervous system arousal occurred more frequently with lisdexamfetamine than placebo (relative risk range, 1.63 to 4.28). Other forms of cognitive behavioral therapy and topiramate also increased abstinence and reduced binge-eating frequency and related psychopathology. Topiramate reduced weight and increased sympathetic nervous system arousal, and lisdexamfetamine reduced weight and appetite. Limitations Most study participants were overweight or obese white women aged 20 to 40 years. Many treatments were examined only in single studies. Outcomes were measured inconsistently across trials and rarely

  4. Binge-Eating Disorder in Adults: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Brownley, Kimberly A; Berkman, Nancy D; Peat, Christine M; Lohr, Kathleen N; Cullen, Katherine E; Bann, Carla M; Bulik, Cynthia M

    2016-09-20

    The best treatment options for binge-eating disorder are unclear. To summarize evidence about the benefits and harms of psychological and pharmacologic therapies for adults with binge-eating disorder. English-language publications in EMBASE, the Cochrane Library, Academic OneFile, CINAHL, and ClinicalTrials.gov through 18 November 2015, and in MEDLINE through 12 May 2016. 9 waitlist-controlled psychological trials and 25 placebo-controlled trials that evaluated pharmacologic (n = 19) or combination (n = 6) treatment. All were randomized trials with low or medium risk of bias. 2 reviewers independently extracted trial data, assessed risk of bias, and graded strength of evidence. Therapist-led cognitive behavioral therapy, lisdexamfetamine, and second-generation antidepressants (SGAs) decreased binge-eating frequency and increased binge-eating abstinence (relative risk, 4.95 [95% CI, 3.06 to 8.00], 2.61 [CI, 2.04 to 3.33], and 1.67 [CI, 1.24 to 2.26], respectively). Lisdexamfetamine (mean difference [MD], -6.50 [CI, -8.82 to -4.18]) and SGAs (MD, -3.84 [CI, -6.55 to -1.13]) reduced binge-eating-related obsessions and compulsions, and SGAs reduced symptoms of depression (MD, -1.97 [CI, -3.67 to -0.28]). Headache, gastrointestinal upset, sleep disturbance, and sympathetic nervous system arousal occurred more frequently with lisdexamfetamine than placebo (relative risk range, 1.63 to 4.28). Other forms of cognitive behavioral therapy and topiramate also increased abstinence and reduced binge-eating frequency and related psychopathology. Topiramate reduced weight and increased sympathetic nervous system arousal, and lisdexamfetamine reduced weight and appetite. Most study participants were overweight or obese white women aged 20 to 40 years. Many treatments were examined only in single studies. Outcomes were measured inconsistently across trials and rarely assessed beyond end of treatment. Cognitive behavioral therapy, lisdexamfetamine, SGAs, and topiramate reduced

  5. Pressure profiles of plasmas confined in the field of a magnetic dipole

    International Nuclear Information System (INIS)

    Davis, Matthew S; Mauel, M E; Garnier, Darren T; Kesner, Jay

    2014-01-01

    Equilibrium pressure profiles of plasmas confined in the field of a dipole magnet are reconstructed using magnetic and x-ray measurements on the levitated dipole experiment (LDX). LDX operates in two distinct modes: with the dipole mechanically supported and with the dipole magnetically levitated. When the dipole is mechanically supported, thermal particles are lost along the field to the supports, and the plasma pressure is highly peaked and consists of energetic, mirror-trapped electrons that are created by electron cyclotron resonance heating. By contrast, when the dipole is magnetically levitated losses to the supports are eliminated and particles are lost via slower cross-field transport that results in broader, but still peaked, plasma pressure profiles. (paper)

  6. Safety of pharmacotherapy options for bulimia nervosa and binge eating disorder.

    Science.gov (United States)

    Bello, Nicholas T; Yeomans, Bryn L

    2018-01-01

    Eating disorders represent a set of psychiatric illnesses with lifelong complications and high relapse rates. Individuals with eating disorders are often stigmatized and clinicians have a limited set of treatments options. Pharmacotherapy has the potential to improve long term compliance and patient commitment to treatment for eating disorders. Areas covered: This review will examine the efficacy and safety profile of the FDA-approved medications for the treatment of bulimia nervosa (BN) and binge eating disorder (BED). This will include the evaluation of fluoxetine for BN, and lisdexamfetamine for BED. Safety information will be review from randomized control trials (RCT), open label trials, and case reports. Expert opinion: Fluoxetine for BN and lisdexamfetamine for BED are relatively safe and well-tolerated. Despite these properties, these two medications represent a limited arsenal for the pharmacological treatment of eating disorders. Thus, more research-based strategies are needed to develop safe, effective, and more targeted therapies for eating disorders.

  7. Microcomputer-Assisted Flow-Through ASV System.

    Science.gov (United States)

    1979-09-01

    FXVAL AND LPTNO,LXVAL *RETURN I-TRUE 0-FALSE IN ACCA *T VALUE ON LINE IS LEFT IN Y 0390 FE 0033 D AELINE LDX FPTNO /GET Ti 0393 09 DIX 1ST Y VALUE 0394...64D6 9 DEX 04D7 26 F3 04D4 SNE CLSA1 04D9 39 RTS *SAVE THE INTEGRATION RESULTS IN PROPER BUFFER ***** ** *** k******* 04DA 36 6633 D SAYRES LDAA ELN

  8. The Levitation Control System for the Levitated Dipole Experiment

    Science.gov (United States)

    Garnier, D. T.; Hansen, A. K.; Mauel, M. E.; Pedersen, T. Sunn; Dagen, S.; Kesner, J.; Liptac, J.

    2001-10-01

    The confining field in the Levitated Dipole Experiment (LDX) is provided by a 1/2 ton levitated superconducting dipole magnet. This floating coil is charged with 1.5 MA current and will be levitated continuously for the eight hour experimental run day. Earnshaw's theorem states that there exists no statically stable configuration for levitation of magnets. In LDX, the floating coil is levitated by a smaller dipole levitation coil 1.5 meters above. This configuration is unstable vertically, but stable in tilt or horizontal motion. The position of the coil will be monitored with a set of eight laser position detectors giving redundant measurements of the five degrees of freedom of the floating coil. The levitation will then be stabilized by feedback control of the current in the levitation coil. The feedback system is a digital system running on a real time operating system platform. This system is programmed, monitored, and controlled by a second computer using Matlab Simulink. The system is currently being tested on a small model and a larger test is planned before LDX operation. Results from these tests and optimizations will be presented.

  9. Amphetamine, past and present--a pharmacological and clinical perspective.

    Science.gov (United States)

    Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-06-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine's diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine's distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.

  10. The effects of laser welding parameters on the microstructure of ferritic and duplex stainless steels welds

    Science.gov (United States)

    Pekkarinen, J.; Kujanpää, V.

    This study is focused to determine empirically, which microstructural changes occur in ferritic and duplex stainless steels when heat input is controlled by welding parameters. Test welds were done autogenously bead-on-plate without shielding gas using 5 kW fiber laser. For comparison, some gas tungsten arc welds were made. Used test material were 1.4016 (AISI 430) and 1.4003 (low-carbon ferritic) type steels in ferritic steels group and 1.4162 (low-alloyed duplex, LDX2101) and 1.4462 (AISI 2205) type steels in duplex steels group. Microstructural changes in welds were identified and examined using optical metallographic methods.

  11. Investigation of selective corrosion resistance of aged lean duplex stainless steel 2101 by non-destructive electrochemical techniques

    International Nuclear Information System (INIS)

    Gao Juan; Jiang Yiming; Deng Bo; Zhang Wei; Zhong Cheng; Li Jin

    2009-01-01

    Lean duplex stainless steel 2101 (LDX2101) shows wide application potential due to its better corrosion performance and lower cost than traditional 304 austenite steel. This paper investigates the effects of thermal aging treatments at 700 deg. C for various aging times up to 100 h on the selective corrosion resistance of LDX2101 by two non-destructive electrochemical measurements: double-loop electrochemical potentiokinetic reactivation (DL-EPR) and electrochemical impedance spectroscopy (EIS). The evolution of microstructure was examined by optical microscopy, SEM microscopy and X-ray diffraction techniques (XRD). The results showed that the two applied electrochemical measurements agreed very well. Both methods were able to reveal the relationship between microstructure and selective corrosion resistance, which was related to the formation of chromium- and molybdenum-depleted zones around the precipitates, especially the σ phase, during aging. Nevertheless, more information could be obtained using EIS methods, including the interfacial charge transfer reaction and the corrosion product adsorption process. The results suggest that the susceptibility of the aged alloy to selective corrosion is presumably codetermined by the formation of chromium- and molybdenum-depleted areas, as well as by the replenishment of them, in these areas from the bulk during aging.

  12. Comparative Effectiveness of Treatments for Binge-Eating Disorder: Systematic Review and Network Meta-Analysis.

    Science.gov (United States)

    Peat, Christine M; Berkman, Nancy D; Lohr, Kathleen N; Brownley, Kimberly A; Bann, Carla M; Cullen, Katherine; Quattlebaum, Mary J; Bulik, Cynthia M

    2017-09-01

    Psychological and pharmacological interventions for binge-eating disorder have previously demonstrated efficacy (compared with placebo or waitlist control); thus, we aimed to expand that literature with a review of comparative effectiveness. We searched MEDLINE,® EMBASE,® Cochrane Library, Academic OneFile, CINAHL® for binge-eating disorder treatment articles and selected studies using predetermined inclusion and exclusion criteria. Data were sufficient for network meta-analysis comparing two pharmacological interventions; psychological interventions were analysed qualitatively. In all, 28 treatment comparisons were included in this review: one pharmacological comparison (second-generation antidepressants versus lisdexamfetamine) and 26 psychological comparisons. Only three statistically significant differences emerged: lisdexamfetamine was better at increasing binge abstinence than second-generation antidepressants; therapist-led cognitive behavioural therapy was better at reducing binge-eating frequency than behavioural weight loss, but behavioural weight loss was better at reducing weight. The majority of other treatment comparisons revealed few significant differences between groups. Thus, patients and clinicians can choose from several effective treatment options. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

  13. Are there any potentially dangerous pharmacological effects of combining ADHD medication with alcohol and drugs of abuse? A systematic review of the literature.

    Science.gov (United States)

    Barkla, Xanthe M; McArdle, Paul A; Newbury-Birch, Dorothy

    2015-10-30

    Among young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood. ADHD is associated with increased risk of co-morbid psychiatric disorders, including substance misuse. Many will be prescribed medication, namely methylphenidate, atomoxetine, dexamphetamine and lisdexamfetamine. If so, it is important to know if interactions exist and if they are potentially toxic. Three databases (Medline, EMBASE and PsychINFO) from a 22 year period (1992 - June 2014) were searched systematically. Key search terms included alcohol, substance related disorders, methylphenidate, atomoxetine, dexamphetamine, lisdexamfetamine, and death, which identified 493 citations (344 after removal of duplicates). The eligibility of each study was assessed jointly by two investigators, leaving 20 relevant articles. We identified only a minimal increase in side-effects when ADHD medication (therapeutic doses) was taken with alcohol. None of the reviewed studies showed severe sequelae among those who had overdosed on ADHD medication and other coingestants, including alcohol. The numbers across all the papers studied remain too low to exclude uncommon effects. Also, studies of combined effects with novel psychoactive substances have not yet appeared in the literature. Nevertheless, no serious sequelae were identified from combining ADHD medication with alcohol/illicit substances from the pre-novel psychoactive substance era.

  14. Amphetamine, past and present – a pharmacological and clinical perspective

    Science.gov (United States)

    Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-01-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine’s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed. PMID:23539642

  15. New Calix[4]arene dibenzocrown ethers for selective sensing of cesium ion in aqueous environment

    International Nuclear Information System (INIS)

    Kim, Jong Seung; Kim, Jong Kuk; Choi, Wang Kyu; Lee, Kune Woo; Oh, Won Jin

    1997-01-01

    1,3-dialkoxycalix[4]arene dibenzocrown ethers (6-9) were successfully synthesized in the fixed 1,3-alternate conformation with over 90% yields by the reaction of corresponding 1,3dialkoxycalix[4]arenes 2-5 with dibenzodimesylate 13 in acetonitrile as a solvent in the presence of cesium carbonate as a base. In view of cyclization yield, the use of dimesylate is found to be better than that of dibenzoditosylate. With an unusual AB pattern in 1 H NMR spectrum for compound 9, it is suggested that conformational structure of 1,3-diallyloxycalix[4]arene dibenzocrown ether be less flexible than that of usual 1,3-alternate calixcrown ether, probably due to steric effects of two ally1 group. Complexation of the corresponding calix[4]arene 6-9 toward alkali metal ions using single flux method through bulk liquid membrane system was found to give a high cesium selectivity. 28 refs., 1 tab., 1 fig

  16. Anelastic mechanical loss spectrometry of hydrogen in austenitic stainless steels

    International Nuclear Information System (INIS)

    Yagodzinskyy, Y.; Andronova, E.; Ivanchenko, M.; Haenninen, H.

    2009-01-01

    Atomic distribution of hydrogen, its elemental diffusion jumps and its interaction with dislocations in a number of austenitic stainless steels are studied with anelastic mechanical loss (AML) spectrometry in combination with the hydrogen thermal desorption method. Austenitic stainless steels of different chemical composition, namely, AISI 310, AISI 201, and AISI 301LN, as well as LDX 2101 duplex stainless steel are studied to clarify the role of different alloying elements on the hydrogen behavior. Activation analyses of the hydrogen Snoek-like peaks are performed with their decomposition to sets of Gaussian components. Fine structure of the composite hydrogen peaks is analyzed under the assumption that each component corresponds to diffusion transfer of hydrogen between octahedral positions with certain atomic compositions of the nearest neighbouring lattice sites. An additional component originating from hydrogen-dislocation interaction is considered. Binding energies for hydrogen-dislocation interaction are also estimated for the studied austenitic stainless steels.

  17. Weld oxide formation on lean duplex stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Westin, E.M. [Outokumpu Stainless, Avesta Research Centre, P.O. Box 74, SE-774 22 Avesta (Sweden)], E-mail: elin.westin@outokumpu.com; Olsson, C.-O.A. [Outokumpu Stainless, Avesta Research Centre, P.O. Box 74, SE-774 22 Avesta (Sweden); Hertzman, S. [Outokumpu Stainless Research Foundation, Brinellvaegen 23, SE-100 44 Stockholm (Sweden)

    2008-09-15

    Weld oxides have a strong influence on corrosion resistance, but have hitherto only been studied to a limited extent for duplex stainless steels. X-ray photoelectron spectroscopy (XPS) has here been used to study heat tint formed on gas tungsten arc (GTA) welds on the commercial duplex grades LDX 2101 (EN 1.4162/UNS S32101) and 2304 (EN 1.4362/UNS S32304) welded with and without nitrogen additions to the shielding gas. The process of heat tint formation is discussed in terms of transport phenomena to explain the effect of atmosphere, temperature and composition. The oxides formed were found to be enriched in manganese and corrosion testing shows that nitrogen has a strong influence on the weld oxide. A mechanism is proposed including evaporation from the weld pool and subsequent redeposition.

  18. Weld oxide formation on lean duplex stainless steel

    International Nuclear Information System (INIS)

    Westin, E.M.; Olsson, C.-O.A.; Hertzman, S.

    2008-01-01

    Weld oxides have a strong influence on corrosion resistance, but have hitherto only been studied to a limited extent for duplex stainless steels. X-ray photoelectron spectroscopy (XPS) has here been used to study heat tint formed on gas tungsten arc (GTA) welds on the commercial duplex grades LDX 2101 (EN 1.4162/UNS S32101) and 2304 (EN 1.4362/UNS S32304) welded with and without nitrogen additions to the shielding gas. The process of heat tint formation is discussed in terms of transport phenomena to explain the effect of atmosphere, temperature and composition. The oxides formed were found to be enriched in manganese and corrosion testing shows that nitrogen has a strong influence on the weld oxide. A mechanism is proposed including evaporation from the weld pool and subsequent redeposition

  19. Pharmacologic Treatments for Binge-Eating Disorder.

    Science.gov (United States)

    McElroy, Susan L

    2017-01-01

    Binge-eating disorder (BED) is the most common eating disorder and is associated with poor physical and mental health outcomes. Psychological and behavioral interventions have been a mainstay of treatment for BED, but as understanding of this disorder has grown, pharmacologic agents have become promising treatment options for some patients. At this time, only one drug-the stimulant prodrug lisdexamfetamine-is approved for the treatment of BED. Numerous classes of medications including antidepressants, anticonvulsants, and antiobesity drugs have been explored as off-label treatments for BED with variable success. Although not all patients with BED may be suitable candidates for pharmacotherapy, all patients should be considered for and educated about pharmacologic treatment options. © Copyright 2017 Physicians Postgraduate Press, Inc.

  20. Update on therapy for narcolepsy.

    Science.gov (United States)

    Thorpy, Michael J

    2015-05-01

    Narcolepsy is a severe, incurable, neurological disorder that is treated by pharmacological management of its symptoms. The main symptoms are excessive daytime sleepiness (EDS) and cataplexy, although addition symptoms that may require treatment include sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep. Sodium oxybate and modafinil/armodafinil are the first-line treatments for EDS, and sodium oxybate for cataplexy. Sodium oxybate treats all the symptoms of narcolepsy, whereas modafinil is effective for EDS only. Alternative medications for EDS include methylphenidate or amphetamines such as dextroamphetamine, lisdexamfetamine, methamphetamine, or combination amphetamine salts. Non-FDA approved medications for cataplexy include norepinephrine reuptake inhibitors such as venlafaxine or atomoxetine. Combination therapy can be more effective for sleepiness such as sodium oxybate and modafinil/armodafinil. Medication for narcolepsy is generally well tolerated and usually required life-long although does not eliminate all symptoms of narcolepsy.

  1. Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys.

    Science.gov (United States)

    Johnson, Amy R; Banks, Matthew L; Blough, Bruce E; Lile, Joshua A; Nicholson, Katherine L; Negus, S Stevens

    2016-08-01

    Homologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper. Four rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43mg/kg/injection) and food (0, 1, 3, or 10 1g banana-flavored food pellets). During daily 5h sessions, a single cocaine dose and a single food-reinforcer magnitude were available in 10 30-min trials. During the initial "sample" trial, the available cocaine and food reinforcer were delivered non-contingently. During each of the subsequent nine "choice" trials, responding could produce either the cocaine or food reinforcer under an independent concurrent progressive-ratio schedule. Preference was governed by the cocaine dose and food-reinforcer magnitude, and increasing cocaine doses produced dose-dependent increases in cocaine choice at all food-reinforcer magnitudes. Effects of the candidate medication lisdexamfetamine (0.32-3.2mg/kg/day) were then examined on choice between 0.14mg/kg/injection cocaine and 10 pellets. Under baseline conditions, this reinforcer pair maintained an average of approximately 6 cocaine and 3 food choices. Lisdexamfetamine dose-dependently decreased cocaine choice in all monkeys, but food choice was not significantly altered. These results support utility of this procedure in rhesus monkeys as one component of a platform for translational research on medications development to treat cocaine use disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Chiral analysis of amphetamines in hair by liquid chromatography-tandem mass spectrometry: compliance-monitoring of attention deficit hyperactivity disorder (ADHD) patients under Elvanse® therapy and identification after controlled low-dose application.

    Science.gov (United States)

    Binz, Tina M; Williner, Elena; Strajhar, Petra; Dolder, Patrick C; Liechti, Matthias E; Baumgartner, Markus R; Kraemer, Thomas; Steuer, Andrea E

    2018-02-01

    Amphetamine (AMP) is used as an illicit drug and also for the treatment of attention deficit hyperactivity disorder (ADHD). Respective drugs most often contain the enantiomer (S)-AMP as active compound or (S)-AMP is formed from the prodrug lisdexamfetamine (Elvanse®) whereas the illicit drug is usually traded as racemate ((R/S)-AMP). A differentiation between the use of the medically prescribed drug and the abuse of illicit street amphetamine is of great importance, for example in retrospective consumption monitoring by hair analysis. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the chiral separation and quantitation of (S)- and (R)-AMP in hair was developed. For this purpose, 20 mg hair was extracted and derivatized with N-(2,4-dinitro-5-fluorophenyl)-L(S)-valinamide L(S)-(DNPV) to yield amphetamine diastereomers. Baseline separation of the resulting diastereomers was achieved on a high-pressure liquid-chromatography system (HPLC) coupled to a Sciex QTRAP® 5500 linear ion trap quadrupole mass spectrometer. The method was successfully validated. Analysis of hair samples from nine Elvanse® patients revealed only (S)-AMP in eight cases; one subject showed both enantiomers indicating a (side-) consumption of street amphetamine. The analysis of the 16 amphetamine users' samples showed only racemic amphetamine. Furthermore, it could be shown in a controlled study that (S)-AMP can be detected after administration of even very low doses of lisdexamfetamine and dexamphetamine, which can be of interest in forensic toxicology and especially in drug-facilitated crime (DFC). The method now enables the retrospective compliance-monitoring of ADHD patients and the differentiation between medically prescribed intake of (S)-amphetamine and abuse of illicit street amphetamine. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Medical school gift restriction policies and physician prescribing of newly marketed psychotropic medications: difference-in-differences analysis.

    Science.gov (United States)

    King, Marissa; Essick, Connor; Bearman, Peter; Ross, Joseph S

    2013-01-30

    To examine the effect of attending a medical school with an active policy on restricting gifts from representatives of pharmaceutical and device industries on subsequent prescribing behavior. Difference-in-differences approach. 14 US medical schools with an active gift restriction policy in place by 2004. Prescribing patterns in 2008 and 2009 of physicians attending one of the schools compared with physicians graduating from the same schools before the implementation of the policy, as well as a set of contemporary matched controls. Probability that a physician would prescribe a newly marketed medication over existing alternatives of three psychotropic classes: lisdexamfetamine among stimulants, paliperidone among antipsychotics, and desvenlafaxine among antidepressants. None of these medications represented radical breakthroughs in their respective classes. For two of the three medications examined, attending a medical school with an active gift restriction policy was associated with reduced prescribing of the newly marketed drug. Physicians who attended a medical school with an active conflict of interest policy were less likely to prescribe lisdexamfetamine over older stimulants (adjusted odds ratio 0.44, 95% confidence interval 0.22 to 0.88; P=0.02) and paliperidone over older antipsychotics (0.25, 0.07 to 0.85; P=0.03). A significant effect was not observed for desvenlafaxine (1.54, 0.79 to 3.03; P=0.20). Among cohorts of students who had a longer exposure to the policy or were exposed to more stringent policies, prescribing rates were further reduced. Exposure to a gift restriction policy during medical school was associated with reduced prescribing of two out of three newly introduced psychotropic medications.

  4. New Calix[4]arene dibenzocrown ethers for selective sensing of cesium ion in aqueous environment

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Seung; Kim, Jong Kuk [Konyang University, Nonsan (Korea, Republic of); Choi, Wang Kyu; Lee, Kune Woo; Oh, Won Jin [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1997-12-31

    1,3-dialkoxycalix[4]arene dibenzocrown ethers (6-9) were successfully synthesized in the fixed 1,3-alternate conformation with over 90% yields by the reaction of corresponding 1,3dialkoxycalix[4]arenes 2-5 with dibenzodimesylate 13 in acetonitrile as a solvent in the presence of cesium carbonate as a base. In view of cyclization yield, the use of dimesylate is found to be better than that of dibenzoditosylate. With an unusual AB pattern in {sup 1}H NMR spectrum for compound 9, it is suggested that conformational structure of 1,3-diallyloxycalix[4]arene dibenzocrown ether be less flexible than that of usual 1,3-alternate calixcrown ether, probably due to steric effects of two ally1 group. Complexation of the corresponding calix[4]arene 6-9 toward alkali metal ions using single flux method through bulk liquid membrane system was found to give a high cesium selectivity. 28 refs., 1 tab., 1 fig.

  5. Development of a lean duplex stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Liljas, M.; Johansson, P.; Liu Hui-Ping; Olsson, C.O.A. [Avesta Research Centre, Avesta (Sweden). Outokumpu Stainless

    2008-06-15

    The classic series of duplex stainless steels shows very high corrosion resistance and can be used for very demanding applications. A new lean duplex steel, LDX 2101 {sup registered} (EN 1.4162, UNS S32101), has been developed with corrosion resistance on a par with standard austenitic grades. Application areas include: structural components, chemical industry, tanks and containers. The steel was designed to have equal amounts of ferrite and austenite in annealed condition and with an austenite that is stable against strain-induced martensite. Thanks to its high nitrogen content, the steel has a fast austenite reformation when subjected to thermal cycling, e.g. welding. Unlike conventional duplex grades, the formation of intermetallic phase is very sluggish, although precipitation of nitrides and carbides has a certain impact on material properties after exposure in the temperature range 600 to 800 C. The precipitation behaviour after different isothermal treatments is described and its influence on different product properties is shown. A good agreement was found between impact toughness and corrosion resistance for a wide range of thermal treatments. (orig.)

  6. Rightfulness of Summation Cut-Offs in the Albedo Problem with Gaussian Fluctuations of the Density of Scatterers

    Science.gov (United States)

    Selim, M. M.; Bezák, V.

    2003-06-01

    The one-dimensional version of the radiative transfer problem (i.e. the so-called rod model) is analysed with a Gaussian random extinction function (x). Then the optical length X = 0 Ldx(x) is a Gaussian random variable. The transmission and reflection coefficients, T(X) and R(X), are taken as infinite series. When these series (and also when the series representing T 2(X), T 2(X), R(X)T(X), etc.) are averaged, term by term, according to the Gaussian statistics, the series become divergent after averaging. As it was shown in a former paper by the authors (in Acta Physica Slovaca (2003)), a rectification can be managed when a `modified' Gaussian probability density function is used, equal to zero for X > 0 and proportional to the standard Gaussian probability density for X > 0. In the present paper, the authors put forward an alternative, showing that if the m.s.r. of X is sufficiently small in comparison with & $bar X$ ; , the standard Gaussian averaging is well functional provided that the summation in the series representing the variable T m-j (X)R j (X) (m = 1,2,..., j = 1,...,m) is truncated at a well-chosen finite term. The authors exemplify their analysis by some numerical calculations.

  7. Size-separated particle fractions of stainless steel welding fume particles - A multi-analytical characterization focusing on surface oxide speciation and release of hexavalent chromium.

    Science.gov (United States)

    Mei, N; Belleville, L; Cha, Y; Olofsson, U; Odnevall Wallinder, I; Persson, K-A; Hedberg, Y S

    2018-01-15

    Welding fume of stainless steels is potentially health hazardous. The aim of this study was to investigate the manganese (Mn) and chromium (Cr) speciation of welding fume particles and their extent of metal release relevant for an inhalation scenario, as a function of particle size, welding method (manual metal arc welding, metal arc welding using an active shielding gas), different electrodes (solid wires and flux-cored wires) and shielding gases, and base alloy (austenitic AISI 304L and duplex stainless steel LDX2101). Metal release investigations were performed in phosphate buffered saline (PBS), pH 7.3, 37°, 24h. The particles were characterized by means of microscopic, spectroscopic, and electroanalytical methods. Cr was predominantly released from particles of the welding fume when exposed in PBS [3-96% of the total amount of Cr, of which up to 70% as Cr(VI)], followed by Mn, nickel, and iron. Duplex stainless steel welded with a flux-cored wire generated a welding fume that released most Cr(VI). Nano-sized particles released a significantly higher amount of nickel compared with micron-sized particle fractions. The welding fume did not contain any solitary known chromate compounds, but multi-elemental highly oxidized oxide(s) (iron, Cr, and Mn, possibly bismuth and silicon). Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. The elaboration of a mapping during the emergency phase: the example of the Fukushima NPS

    International Nuclear Information System (INIS)

    Isnard, O.

    2012-01-01

    On March 11. 2011, a powerful earthquake and tsunami hit the northeast coast of Japan which seriously damaged the Fukushima Dai-Ichi Nuclear Power Plant and caused a radiological emergency. This situation was instantaneously brought at an international scale were many states started to assess the situation. IRSN (Institute of Radioprotection and Nuclear Safety), in its role of technical advisers of the French government activated its technical emergency centre immediately and started producing expertise on the accident and its radiological consequences. In order to assess air contamination levels, IRSN made real time preliminary evaluations of the radioactivity quantity that may have been released over the period from 12 to 22 March 2011 by the three damaged reactors. IRSN has simulated the atmospheric dispersion of estimated releases emitted between 12 and 22 March using its long-range full 3-dimensional Eulerian operational numerical model (a scale of several hundred kilometers) ldX, the meteorological forecasts input were provided by the Meteo-France model ARPEGE. This simulation was made with the source term defined previously in order to be able to evaluate the radiological consequences. During more than 6 weeks, the IRSN emergency centre was operational and gave on a daily basis, analysis and prognosis of the situation on the reactors of the Fukushima site but also on the radiological consequences on the environment. The paper is followed by the slides of the presentation

  9. Multi point of care instrument evaluation for use in anti-retroviral clinics in South Africa.

    Science.gov (United States)

    Gounden, Verena; George, Jaya

    2012-01-01

    South Africa has the largest prevalence of HIV infected individuals in the world. The introduction of point of care testing to anti-retroviral (ARV) clinic sites is hoped to fast track initiation of patients on ARVs and to allow for earlier recognition of adverse effects such as dyslipidaemia, renal and hepatic dysfunction. We evaluated six instruments for the following analytes: glucose, lactate, creatinine, cholesterol, triglycerides, HDL-cholesterol, alanine transaminase (ALT), and glycated haemoglobin. Comparisons with the central laboratory analyser were performed as well as precision studies. A scoring system was developed by the authors to evaluate the instruments in terms of analytical performance, cost, ease of use, and other operational characteristics. As one of the goals of the placement of these instruments was that their operation was simple enough to be used by non-laboratory staff, ease of use contributed a large proportion to the final scoring. Analytical performance of the POC analysers were generally similar, however, there were significant differences in operational characteristics and ease of use. Bias for the different analytes when compared to the laboratory analyser ranged from -27% to 14%. Calculated total errors for all analytes except for HDL cholesterol were within total allowable error recommendations. The two instruments (Roche Reflotron and Cholestech LDX) with the highest overall total points achieved the highest scores for ease of use. This pilot study has led to the development of a scoring system for the evaluation of POC instruments.

  10. Adult Attention-Deficit/Hyperactivity Disorder (ADHD) and Insomnia: an Update of the Literature.

    Science.gov (United States)

    Wynchank, Dora; Bijlenga, Denise; Beekman, Aartjan T; Kooij, J J Sandra; Penninx, Brenda W

    2017-10-30

    Insomnia is diagnosed when there is dissatisfaction with sleep quantity or quality. It has a prevalence in the general population ranging from 31 to 56%. Insomnia has previously been associated with adult attention-deficit/hyperactivity disorder (ADHD). In this review, we address three topics: (1) the cross-sectional relationship between ADHD and insomnia in adulthood, (2) the longitudinal relationship between ADHD and insomnia, and (3) insomnia as a side effect of pharmacological treatments for adult ADHD. Three cross-sectional, clinical, and population studies report a prevalence of insomnia in ADHD adults ranging from 43 to 80%. Longitudinal evidence for a link between childhood-onset ADHD and insomnia at later age is mixed, with one study confirming and another study not supporting such a longitudinal association. In randomized, placebo-controlled trials, insomnia is reported significantly more often in the treatment arm than in the placebo arm. In varying percentages of trial participants, insomnia is a treatment-emergent adverse effect in triple-bead mixed amphetamine salts (40-45%), dasotraline (35-45%), lisdexamfetamine (10-19%), and extended-release methylphenidate (11%). Ten to seventeen percent of subjects in placebo-controlled trials of atomoxetine report insomnia, possibly related to poor metabolizer status. The mechanisms explaining the relationship between ADHD and sleep problems are incompletely understood, but both genetic and non-shared environmental influences may be involved. Adults with ADHD should be assessed for insomnia, which is frequently comorbid, and both conditions should be treated.

  11. Emerging Treatments in Eating Disorders.

    Science.gov (United States)

    Lutter, Michael

    2017-07-01

    Eating disorders (EDs), including anorexia nervosa, bulimia nervosa, and binge-eating disorder, constitute a class of common and deadly psychiatric disorders. While numerous studies in humans highlight the important role of neurobiological alterations in the development of ED-related behaviors, the precise neural substrate that mediates this risk is unknown. Historically, pharmacological interventions have played a limited role in the treatment of eating disorders, typically providing symptomatic relief of comorbid psychiatric issues, like depression and anxiety, in support of the standard nutritional and psychological treatments. To date there are no Food and Drug Administration-approved medications or procedures for anorexia nervosa, and only one Food and Drug Administration-approved medication each for bulimia nervosa (fluoxetine) and binge-eating disorder (lisdexamfetamine). While there is little primary interest in drug development for eating disorders, postmarket monitoring of medications and procedures approved for other indications has identified several novel treatment options for patients with eating disorders. In this review, I utilize searches of the PubMed and ClinicalTrials.gov databases to highlight emerging treatments in eating disorders.

  12. Pharmacotherapy of eating disorders.

    Science.gov (United States)

    Davis, Haley; Attia, Evelyn

    2017-11-01

    Medications are commonly prescribed in the treatment of eating disorders. In this review, we discuss relevant medications used for the treatment of bulimia nervosa, binge eating disorder (BED), and anorexia nervosa. We focus on recent research developments, where applicable, in addition to discussing important findings from older studies to provide a complete synopsis of the current evidence base for eating disorder treatment using pharmacologic agents. Medications are generally useful for patients with bulimia nervosa and BED. For bulimia nervosa, antidepressant medications are the primary pharmacologic treatment and limited new research has been completed. For BED, lisdexamfetamine is reported to be generally well tolerated and effective, and is the first medication to be indicated by the US Food and Drug Administration for treatment of BED. For anorexia nervosa, there is limited evidence supporting benefits of medications. Second-generation antipsychotics, particularly olanzapine, appear to demonstrate some benefit for weight gain in anorexia nervosa, although are not advised as a stand-alone treatment. Transdermal administration of hormonal agents is also being explored for improving bone health in anorexia nervosa. Although pharmacotherapy has established utility in bulimia nervosa and BED, further research on medications for the treatment of eating disorders, particularly anorexia nervosa, is necessary.

  13. Gateways to clinical trials.

    Science.gov (United States)

    Tomillero, A; Moral, M A

    2009-05-01

    (-)-Gossypol; Abacavir sulfate/lamivudine, ACAM-1000, ACE-011, Agomelatine, AGS-004, Alemtuzumab, Alvocidib hydrochloride, AMG-317, Amlodipine, Aripiprazole, Atazanavir sulfate, Azacitidine; Becatecarin, Belinostat, Bevacizumab, BMS-387032, BMS-690514, Bortezomib; Casopitant mesylate, Cetuximab, Choline fenofibrate, CK-1827452, Clofarabine, Conivaptan hydrochloride; Dabigatran etexilate, DADMe-Immucillin-H, Darbepoetin alfa, Darunavir, Dasatinib, DC-WT1, Decitabine, Deferasirox, Degarelix acetate, Denenicokin, Denosumab, Dienogest, Duloxetine hydrochloride; Ecogramostim, Eculizumab, Edoxaban tosilate, Elacytarabine, Elesclomol, Eltrombopag olamine, Enfuvirtide, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Etravirine; Flibanserin, Fludarabine, Fondaparinux sodium, Fosamprenavir calcium; Gefitinib, Genistein; I-131-L19-SIP, Idrabiotaparinux sodium, Imatinib mesylate, IMGN-901, Ipilimumab; Laromustine, Lenalidomide, Liposomal cisplatin, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Lopinavir/ritonavir; Maraviroc, MDV-3100, Mecasermin rinfabate, MP-470, Mycophenolic acid sodium salt; Naproxcinod, NB-002, Nesiritide, Nilotinib hydrochloride monohydrate, NK-012; Palonosetron hydrochloride, Panobinostat, Pegfilgrastim, Peginterferon alfa-2a, Pitavastatin calcium, PL-3994, Plerixafor hydrochloride, Plitidepsin, PM-10450; Raltegravir potassium, Recombinant human soluble thrombomodulin, ReoT3D, RHAMM R3 peptide, Rivaroxaban, Romiplostim, Rosuvastatin calcium, Rozrolimupab; Sabarubicin hydrochloride, Salinosporamide A, Sirolimus-eluting stent, Smallpox (Vaccinia) Vaccine, Live, Sorafenib; Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, Tipifarnib, Tipranavir, Trabectedin, Trifluridine/TPI; Vardenafil hydrochloride hydrate, Vinflunine, Volociximab, Vorinostat; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, Zoledronic acid monohydrate

  14. Dopamine and μ-opioid receptor dysregulation in the brains of binge-eating female rats - possible relevance in the psychopathology and treatment of binge-eating disorder.

    Science.gov (United States)

    Heal, David J; Hallam, Michelle; Prow, Michael; Gosden, Jane; Cheetham, Sharon; Choi, Yong K; Tarazi, Frank; Hutson, Peter

    2017-06-01

    Adult, female rats given irregular, limited access to chocolate develop binge-eating behaviour with normal bodyweight and compulsive/perseverative and impulsive behaviours similar to those in binge-eating disorder. We investigated whether (a) dysregulated central nervous system dopaminergic and opioidergic systems are part of the psychopathology of binge-eating and (b) these neurotransmitter systems may mediate the actions of drugs ameliorating binge-eating disorder psychopathology. Binge-eating produced a 39% reduction of striatal D 1 receptors with 22% and 23% reductions in medial and lateral caudate putamen and a 22% increase of striatal μ-opioid receptors. There was no change in D 1 receptor density in nucleus accumbens, medial prefrontal cortex or dorsolateral frontal cortex, striatal D 2 receptors and dopamine reuptake transporter sites, or μ-opioid receptors in frontal cortex. There were no changes in ligand affinities. The concentrations of monoamines, metabolites and estimates of dopamine (dopamine/dihydroxyphenylacetic acid ratio) and serotonin/5-hydroxyindolacetic acid ratio turnover rates were unchanged in striatum and frontal cortex. However, turnover of dopamine and serotonin in the hypothalamus was increased ~20% and ~15%, respectively. Striatal transmission via D 1 receptors is decreased in binge-eating rats while μ-opioid receptor signalling may be increased. These changes are consistent with the attenuation of binge-eating by lisdexamfetamine, which increases catecholaminergic neurotransmission, and nalmefene, a μ-opioid antagonist.

  15. Current pharmacotherapy of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Reddy, D S

    2013-10-01

    Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder in children and adults characterized by a persistent pattern of impulsiveness, inattention and hyperactivity. It affects about 3-10% of children and 2-5% of adolescents and adults and occurs about four times more commonly in boys than girls. The cause of ADHD is unknown, but it has strong genetic and environment components. The first-line treatment options for ADHD include behavioral therapy, pharmacotherapy with stimulants or both. Methylphenidate and amphetamine salts are the stimulant drugs of choice for ADHD treatment. Amphetamines act by increasing presynaptic release of dopamine and other biogenic amines in the brain. Methylphenidate inhibits the reuptake of dopamine and norepinephrine and therefore its pharmacology is identical to that of amphetamines. Lisdex-amfetamine is a prodrug of dextroamphetamine with low feasibility for abuse. Atomoxetine, a selective norepinephrine reuptake inhibitor, is an alternative, non-stimulant drug for ADHD but it is less efficacious than stimulants. Stimulants are generally safe but are associated with adverse effects including headache, insomnia, anorexia and weight loss. There is increased awareness about serious cardiovascular and psychiatric adverse events with ADHD drugs including concern for growth suppression in children. Stimulants have a high potential for abuse and dependence, and should be handled safely to prevent misuse and abuse. Copyright 2013 Prous Science, S.A.U. or its licensors. All rights reserved.

  16. Characterization of ppGalNAc-T18, a member of the vertebrate-specific Y subfamily of UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases.

    Science.gov (United States)

    Li, Xing; Wang, Jing; Li, Wei; Xu, Yingjiao; Shao, Dong; Xie, Yinyin; Xie, Wenxian; Kubota, Tomomi; Narimatsu, Hisashi; Zhang, Yan

    2012-05-01

    The first step of mucin-type O-glycosylation is catalyzed by members of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-T; EC 2.4.1.41) family. Each member of this family has unique substrate specificity and expression profiles. In this report, we describe a new subfamily of ppGalNAc-Ts, designated the Y subfamily. The Y subfamily consists of four members, ppGalNAc-T8, -T9, -T17 and -T18, in which the conserved YDX(5)WGGENXE sequence in the Gal/GalNAc-T motif of ppGalNAc-Ts is mutated to LDX(5)YGGENXE. Phylogenetic analysis revealed that the Y subfamily members only exist in vertebrates. All four Y subfamily members lack in vitro GalNAc-transferase activity toward classical substrates possibly because of the UDP-GalNAc-binding pocket mutants. However, ppGalNAc-T18, the newly identified defining member, was localized in the endoplasmic reticulum rather than the Golgi apparatus in lung carcinoma cells. The knockdown of ppGalNAc-T18 altered cell morphology, proliferation potential and changed cell O-glycosylation. ppGalNAc-T18 can also modulate the in vitro GalNAc-transferase activity of ppGalNAc-T2 and -T10, suggesting that it may be a chaperone-like protein. These findings suggest that the new Y subfamily of ppGalNAc-Ts plays an important role in protein glycosylation; characterizing their functions will provide new insight into the role of ppGalNAc-Ts.

  17. Production and study of high-beta plasma confined by a superconducting dipole magnet

    International Nuclear Information System (INIS)

    Garnier, D.T.; Hansen, A.; Mauel, M.E.; Ortiz, E.; Boxer, A.C.; Ellsworth, J.; Karim, I.; Kesner, J.; Mahar, S.; Roach, A.

    2006-01-01

    The Levitated Dipole Experiment (LDX) [J. Kesner et al., in Fusion Energy 1998, 1165 (1999)] is a new research facility that is exploring the confinement and stability of plasma created within the dipole field produced by a strong superconducting magnet. Unlike other configurations in which stability depends on curvature and magnetic shear, magnetohydrodynamic stability of a dipole derives from plasma compressibility. Theoretically, the dipole magnetic geometry can stabilize a centrally peaked plasma pressure that exceeds the local magnetic pressure (β>1), and the absence of magnetic shear allows particle and energy confinement to decouple. In initial experiments, long-pulse, quasi-steady-state microwave discharges lasting more than 10 s have been produced that are consistent with equilibria having peak beta values of 20%. Detailed measurements have been made of discharge evolution, plasma dynamics and instability, and the roles of gas fueling, microwave power deposition profiles, and plasma boundary shape. In these initial experiments, the high-field superconducting floating coil was supported by three thin supports. The plasma is created by multifrequency electron cyclotron resonance heating at 2.45 and 6.4 GHz, and a population of energetic electrons, with mean energies above 50 keV, dominates the plasma pressure. Creation of high-pressure, high-beta plasma is possible only when intense hot electron interchange instabilities are stabilized by sufficiently high background plasma density. A dramatic transition from a low-density, low-beta regime to a more quiescent, high-beta regime is observed when the plasma fueling rate and confinement time become sufficiently large

  18. A primer on binge eating disorder diagnosis and management.

    Science.gov (United States)

    Citrome, Leslie

    2015-12-01

    Binge eating disorder (BED) is the most common eating disorder, with an estimated lifetime prevalence of 2.6% among U.S. adults, yet often goes unrecognized. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), BED is defined by recurrent episodes of binge eating (eating in a discrete period of time an amount of food larger than most people would eat in a similar amount of time under similar circumstances and a sense of lack of control over eating during the episode), occurring on average at least once a week for 3 months, and associated with marked distress. It can affect both men and women, regardless if they are at normal weight, overweight, or obese, and regardless of their ethnic or racial group. Psychiatric comorbidities are very common, with 79% of adults with BED also experiencing anxiety disorders, mood disorders, impulse control disorders, or substance use disorders; almost 50% of persons with BED have ≥ 3 psychiatric comorbidities. Multiple neurobiological explanations have been proffered for BED, including dysregulation in reward center and impulse control circuitry, with potentially related disturbances in dopamine neurotransmission and endogenous μ-opioid signaling. Additionally, there is interplay between genetic influences and environmental stressors. Psychological treatments such as cognitive behavioral interventions have been recommended as first line and are supported by meta-analytic reviews. Unfortunately, routine medication treatments for anxiety and depression do not necessarily ameliorate the symptoms of BED; however, at present, there is one approved agent for the treatment of moderate to severe BED-lisdexamfetamine, a stimulant that was originally approved for the treatment of attention deficit hyperactivity disorder.

  19. The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety.

    Science.gov (United States)

    Heal, D J; Cheetham, S C; Smith, S L

    2009-12-01

    Results from in vivo techniques, especially intracerebral microdialysis in freely-moving rats, have provided insights into potential mechanisms responsible for the efficacy and safety of catecholaminergic drugs for ADHD treatment. The drugs reviewed come from distinct pharmacological classes: psychostimulant releasing agents, eg d-amphetamine; psychostimulant reuptake inhibitors, eg dl-threo-methylphenidate (dl-MPH), and non-stimulant reuptake inhibitors, eg atomoxetine. Psychostimulants, which currently deliver the best efficacy in treating ADHD, exhibit the following characteristics on extraneuronal catecholamine concentrations in rodent brain in vivo: 1) They enhance the efflux and function of both noradrenaline and dopamine in the central nervous system. 2) The increase of dopamine efflux that they produce is not limited to cortical regions. 3) They have a rapid onset of action with no ceiling on drug effect. d-Amphetamine has a mechanism independent of neuronal firing rate, displacing intraneuronal stores of catecholamines, delaying their reuptake and inhibiting catabolism by monoamine oxidase. dl-MPH has an enigmatic, extraneuronal action that is neuronal firing rate-dependent and reuptake transporter-mediated, yet paradoxically, almost as powerful as that of d-amphetamine. In safety terms, these powerful catecholaminergic effects also make the psychostimulants liable for abuse. Since efficacy and safety derive from the same pharmacological mechanisms, it has not yet been possible to separate these two components. However, the development of once-daily psychostimulant formulations and a prodrug, lisdexamfetamine, has improved patient compliance and markedly reduced scope for their diversion/abuse. This review will discuss the in vivo pharmacological profiles of approved catecholaminergic drugs for treatment of ADHD and implications for their clinical efficacy and abuse liability.

  20. Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline.

    Science.gov (United States)

    McMillin, Matthew; Frampton, Gabriel; Thompson, Michelle; Galindo, Cheryl; Standeford, Holly; Whittington, Eric; Alpini, Gianfranco; DeMorrow, Sharon

    2014-07-10

    Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. These findings suggest that CCL2 is elevated systemically following acute liver injury and that CCL2 is involved in both the

  1. Analysis of body composition and selected lipid parameters in healthy children – a preliminary report

    Directory of Open Access Journals (Sweden)

    Paweł Więch

    2017-09-01

    Full Text Available Aim: The aim of the study was to perform an analytical evaluation of body composition and selected lipid parameters in a population of healthy children. Material and methods: The study included a group of 81 children (44 boys and 37 girls, mean age 11.56 ± 2.84 years participating in a research project in the Centre for Medical and Natural Sciences Research and Innovation in Rzeszow. Body composition measurement (TANITA BC-420 S MA and lipid profile assessment (Cholestech LDX were performed in all patients. Statistical analysis of the collected material was conducted with Statistica 10.0 (StatSoft. Parametric and nonparametric tests were used for statistical analysis of variables. The level of statistical significance was adopted at p < 0.05. Results: A statistically significant difference in fat mass (p < 0.001, fat-free mass (p = 0.003, muscle mass (p = 0.003 and total body water (p < 0.001 was observed between children with normal body weight and overweight or obese children. A significant positive impact of FM (R = 0.09; p = 0.416 and a negative impact of total body water (R = −0.40; p < 0.001 on triglyceride parameters was demonstrated. Additionally, reduced fat mass correlated with a significant increase in high-density lipoprotein (R = −0.29; p = 0.009. Conclusions: The study demonstrated differences in the selected components of body composition in a population of healthy children, which allowed to precisely monitor the nutritional status when correlated with the results of lipid profile.

  2. Emulation of simulations of atmospheric dispersion at Fukushima for Sobol' sensitivity analysis

    Science.gov (United States)

    Girard, Sylvain; Korsakissok, Irène; Mallet, Vivien

    2015-04-01

    Polyphemus/Polair3D, from which derives IRSN's operational model ldX, was used to simulate the atmospheric dispersion at the Japan scale of radionuclides after the Fukushima disaster. A previous study with the screening method of Morris had shown that - The sensitivities depend a lot on the considered output; - Only a few of the inputs are non-influential on all considered outputs; - Most influential inputs have either non-linear effects or are interacting. These preliminary results called for a more detailed sensitivity analysis, especially regarding the characterization of interactions. The method of Sobol' allows for a precise evaluation of interactions but requires large simulation samples. Gaussian process emulators for each considered outputs were built in order to relieve this computational burden. Globally aggregated outputs proved to be easy to emulate with high accuracy, and associated Sobol' indices are in broad agreement with previous results obtained with the Morris method. More localized outputs, such as temporal averages of gamma dose rates at measurement stations, resulted in lesser emulator performances: tests simulations could not satisfactorily be reproduced by some emulators. These outputs are of special interest because they can be compared to available observations, for instance for calibration purpose. A thorough inspection of prediction residuals hinted that the model response to wind perturbations often behaved in very distinct regimes relatively to some thresholds. Complementing the initial sample with wind perturbations set to the extreme values allowed for sensible improvement of some of the emulators while other remained too unreliable to be used in a sensitivity analysis. Adaptive sampling or regime-wise emulation could be tried to circumvent this issue. Sobol' indices for local outputs revealed interesting patterns, mostly dominated by the winds, with very high interactions. The emulators will be useful for subsequent studies. Indeed

  3. Sensitivity study of the wet deposition schemes in the modelling of the Fukushima accident.

    Science.gov (United States)

    Quérel, Arnaud; Quélo, Denis; Roustan, Yelva; Mathieu, Anne; Kajino, Mizuo; Sekiyama, Thomas; Adachi, Kouji; Didier, Damien; Igarashi, Yasuhito

    2016-04-01

    The Fukushima-Daiichi release of radioactivity is a relevant event to study the atmospheric dispersion modelling of radionuclides. Actually, the atmospheric deposition onto the ground may be studied through the map of measured Cs-137 established consecutively to the accident. The limits of detection were low enough to make the measurements possible as far as 250km from the nuclear power plant. This large scale deposition has been modelled with the Eulerian model ldX. However, several weeks of emissions in multiple weather conditions make it a real challenge. Besides, these measurements are accumulated deposition of Cs-137 over the whole period and do not inform of deposition mechanisms involved: in-cloud, below-cloud, dry deposition. A comprehensive sensitivity analysis is performed in order to understand wet deposition mechanisms. It has been shown in a previous study (Quérel et al, 2016) that the choice of the wet deposition scheme has a strong impact on the assessment of the deposition patterns. Nevertheless, a "best" scheme could not be highlighted as it depends on the selected criteria: the ranking differs according to the statistical indicators considered (correlation, figure of merit in space and factor 2). A possibility to explain the difficulty to discriminate between several schemes was the uncertainties in the modelling, resulting from the meteorological data for instance. Since the move of the plume is not properly modelled, the deposition processes are applied with an inaccurate activity in the air. In the framework of the SAKURA project, an MRI-IRSN collaboration, new meteorological fields at higher resolution (Sekiyama et al., 2013) were provided and allows to reconsider the previous study. An updated study including these new meteorology data is presented. In addition, a focus on several releases causing deposition in located areas during known period was done. This helps to better understand the mechanisms of deposition involved following the

  4. A systematic review of cost-effectiveness studies of prevention and treatment for eating disorders.

    Science.gov (United States)

    Le, Long Khanh-Dao; Hay, Phillipa; Mihalopoulos, Cathrine

    2018-04-01

    Eating disorders are serious mental disorders and are associated with substantial economic and social burden. The aim of this study is to undertake a systematic review of the cost-effectiveness studies of both preventive and treatment interventions for eating disorder. Electronic databases (including the Cochrane Controlled Trial Register, MEDLINE, PsycINFO, Academic Search Complete, Global Health, CINAHL complete, Health Business Elite, Econlit, Health Policy Reference Center and ERIC) were searched for published cost-effectiveness studies of eating disorder prevention and treatment including papers published up to January 2017. The quality of studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. In all, 13 studies met the review inclusion criteria as full cost-effectiveness studies and 8 were published since 2011. The studies included three modelled and one trial-based study focused on prevention, two trial-based and one modelled study for anorexia nervosa treatment and three trial-based studies for bulimia nervosa treatment. The remaining studies targeted binge-eating disorder or non-specific eating disorder treatment. The average percent of CHEERS checklist items reported was 71% (standard deviation 21%). Eating disorder interventions were mainly cost-saving or more effective and more costly compared to comparators; however, some results did not reach statistical significance. In the two studies that achieved 100% CHEERS checklist, one study reported that a cognitive dissonance intervention might be cost-effective for prevention of anorexia nervosa and bulimia nervosa with a 90% participation rate and the second study supported lisdexamfetamine to be cost-effective in the treatment of binge-eating disorder. Insufficient evidence for long-term cost-effectiveness (e.g. over 2 years) was found. Cost-effectiveness studies in eating disorder appear to be increasing in number over the last 6 years. Findings

  5. Chemical and enzymatic catalytic routes to polyesters and oligopeptides biobased materials

    Science.gov (United States)

    Zhu, Jianhui

    H comparing to the cationic alternating oligopeptides (KL)x, which is probably due to the short chain length of the oligopeptides. Combination of cationic and anionic alternating oligopeptides has been tested by (KL)x and (LD)x mixtures at 1:1 weight ratio, beta-sheet secondary structure started to appear at neutral pH. The preliminary CD results of the mixtures have shown the potential to manipulate self assembly behavior at different pHs. The second series is alternating oligo(Lys-Trp) targeting for antimicrobial agent design. The alternating (KW)x was successfully synthesized by alpha-chymotrypsin in mixed solvent medium. Chain length of (KW)x can be varied when using different mixed solvent medium. In order to increase the solubility of (KW)x-OEt, C-terminal ethyl ester moiety was modified by reaction with ethylene diamine. Antimicrobial activities of (KW)x with different chain lengths have been tested against E.coli and S. aureus. Our work utilizes a simplified synthetic method to prepare alternating peptides at the cost of chain length uniformity. However, (KW)x-OEt (n=3--6) alternating peptide mixtures still possesses quite good antimicrobial activity while the preparation method is much more easier and greener, which means this method is more economical and environmental friendly. Moreover, the adjustment of reaction conditions and proteases can successfully enhance the control over KW alternating peptide chain length to better achieve more antimicrobial active products. (Abstract shortened by UMI.).

  6. Evaluation of a training program for device operators in the Australian Government's Point of Care Testing in General Practice Trial: issues and implications for rural and remote practices.

    Science.gov (United States)

    Shephard, Mark D; Mazzachi, Beryl C; Watkinson, Les; Shephard, Anne K; Laurence, Caroline; Gialamas, Angela; Bubner, Tanya

    2009-01-01

    From September 2005 to February 2007 the Australian Government funded the Point of Care Testing (PoCT) in General Practice Trial, a multi-centre, cluster randomised controlled trial to determine the safety, clinical effectiveness, cost-effectiveness and satisfaction of PoCT in General Practice. In total, 53 practices (23 control and 30 intervention) based in urban, rural or remote locations across three states (South Australia [SA], New South Wales [NSW] and Victoria [VIC]) participated in the Trial. Control practices had pathology testing performed by their local laboratory, while intervention practices conducted pathology testing by PoCT. In total, 4968 patients (1958 control and 3010 intervention) participated in the Trial. The point-of-care (PoC) tests performed by intervention practices were: haemoglobin A1c (HbA1c) and urine albumin:creatinine ratio (ACR) on patients with diabetes, total cholesterol, triglyceride and high density lipoprotein (HDL) cholesterol on patients with hyperlipidaemia, and international normalised ratio (INR) on patients on anticoagulant therapy. Three PoCT devices measured these tests: the Siemens DCA 2000 (Siemens HealthCare Diagnostics, Melbourne, VIC, Australia) for HbA1c and urine ACR; Point of Care Diagnostics Cholestech LDX analyser (Point of Care Diagnostics; Sydney, NSW, Australia) for lipids; and the Roche CoaguChek S (Roche Diagnostics; Sydney, NSW, Australia) for INR. Point-of-care testing in the General Practice Trial was underpinned by a quality management framework which included an on-going training and competency program for PoCT device operators. This article describes the design, implementation and results of the training and competency program. An education and training resource package was developed for the Trial consisting of a training manual, a set of A3 laminated posters and a CD ROM. Five initial training workshops were held for intervention practices from each geographic region between August and October 2005