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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>Of 290 randomized participants enrolled, 28 received MPH therapy at screening, of which 26 remained symptomatic (ADHD-RS-IV > 18). ADHD-RS-IV total scores, changes from baseline, clinical responsiveness, and rates of symptomatic remission in this subgroup were comparable to the overall population. The safety and tolerability profiles for LDX were comparable to other stimulants currently available.</p> <p>Conclusion</p> <p>In this analysis, children with significant clinical ADHD symptoms despite MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study population.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00556296">NCT00556296</a></p

Mismatches in scale between highly mobile marine megafauna and marine protected areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only < 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed < 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques.Fil: Conners, Melinda G.. University of Washington; Estados Unidos. State University of New York. Stony Brook University; Estados UnidosFil: Sisson, Nicholas B.. Old Dominion University; Estados UnidosFil: Agamboue, Pierre D.. Wildlife Conservation Society; GabónFil: Atkinson, Philip W.. British Trust For Ornithology; Reino UnidoFil: Baylis, Alastair M. M.. Macquarie University; Australia. South Atlantic Environmental Research Institute; Reino UnidoFil: Benson, Scott R.. Noaa National Marine Fisheries Service Southwest Regional Office; Estados Unidos. Moss Landing Marine Laboratories; Estados UnidosFil: Block, Barbara A.. University of Stanford; Estados UnidosFil: Bograd, Steven J.. Noaa National Marine Fisheries Service Southwest Regional Office; Estados UnidosFil: Bordino, Pablo. Mote Marine Laboratory; Estados UnidosFil: Bowen, W.D.. Bedford Institute Of Oceanography, Fisheries And Oceans Canada; Canadá. Dalhousie University Halifax; CanadáFil: Brickle, Paul. South Atlantic Environmental Research Institute; Reino Unido. University of Aberdeen; Reino Unido. University Of Aberdeeen; Reino UnidoFil: Bruno, Ignacio Matias. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: González Carman, Victoria. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Champagne, Cory D.. University of Washington; Estados UnidosFil: Crocker, Daniel E.. Sonoma State University; Estados UnidosFil: Costa, Daniel P.. University of California; Estados UnidosFil: Dawson, Tiffany M.. University Of Central Florida; Estados Unidos. Old Dominion University; Estados UnidosFil: Deguchi, Tomohiro. Yamashina Institute For Ornithology; JapónFil: Dewar, Heidi. Noaa National Marine Fisheries Service Southwest Regional Office; Estados UnidosFil: Doherty, Philip D.. University of Exeter; Reino UnidoFil: Eguchi, Tomo. Noaa National Marine Fisheries Service Southwest Regional Office; Estados UnidosFil: Formia, Angela. Wildlife Conservation Society; Gabón. African Aquatic Conservation Fund; Estados UnidosFil: Godley, Brendan J.. University of Exeter; Reino UnidoFil: Graham, Rachel T.. Maralliance; PanamáFil: Gredzens, Christian. Padre Island National Seashore; Estados UnidosFil: Hart, Kristen M.. United States Geological Survey; Estados UnidosFil: Hawkes, Lucy A.. University of Exeter; Reino UnidoFil: Henderson, Suzanne. Scottish Natural Heritage; Reino UnidoFil: Henry, Robert William. Groundswell Coastal Ecology; Estados UnidosFil: Hückstädt, Luis A.. University of Exeter; Reino Unido. University of California; Estados Unido

A Randomised Controlled Trial of a Play-Based Intervention to Improve the Social Play Skills of Children with Attention Deficit Hyperactivity Disorder (ADHD).

There is a need for effective interventions to address the social difficulties of children with ADHD. This randomised controlled trial examined the effectiveness of a play-based intervention for improving the social play skills of children with ADHD in peer-to-peer interactions. Children with ADHD (5 to 11 years) were randomised to an intervention-first (n = 15) or waitlist control-first group (n = 14). Participants allocated to the control-first group received the intervention after a 10-week wait period. Children invited a typically-developing playmate and parents of children with ADHD participated. The intervention involved: six clinic play-sessions, weekly home-modules and a one-month home follow up. The Test of Playfulness (ToP) was scored by a blinded rater. Parent reported treatment adherence was used to assess treatment fidelity. Between group statistics were used to compare the change of the intervention-first (10-week intervention period) and control-first (10-week wait period) groups. Once all children had received the intervention, repeated measures ANOVA, post hoc Least Significance Difference tests and Cohen's-d were used to measure effect. Changes in ToP social items were analysed using Friedman's ANOVA. Linear regression analyses were used to identify variables that predicted change. The control-first group did not change during the wait period. The change in the intervention-first group was significantly greater than the change in the control-first group (during the wait period). When the data from the two groups were combined, the mean ToP scores of the children with ADHD (n = 29) improved significantly following the intervention, with a large effect from pre to post intervention and from pre intervention to follow up. Children maintained treatment gains at follow up. All ToP social items improved significantly following the intervention. The findings support the use of play involving parent and peer mediated components to enhance the social play skills of children with ADHD. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614000973617

Mismatches in Scale Between Highly Mobile Marine Megafauna and Marine Protected Areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only \u3c 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed \u3c 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques

Mismatches in Scale Between Highly Mobile Marine Megafauna and Marine Protected Areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only \u3c 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed \u3c 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques

Insights into plant biomass conversion from the genome of the anaerobic thermophilic bacterium Caldicellulosiruptor bescii DSM 6725

Caldicellulosiruptor bescii DSM 6725 utilizes various polysaccharides and grows efficiently on untreated high-lignin grasses and hardwood at an optimum temperature of ∼80°C. It is a promising anaerobic bacterium for studying high-temperature biomass conversion. Its genome contains 2666 protein-coding sequences organized into 1209 operons. Expression of 2196 genes (83%) was confirmed experimentally. At least 322 genes appear to have been obtained by lateral gene transfer (LGT). Putative functions were assigned to 364 conserved/hypothetical protein (C/HP) genes. The genome contains 171 and 88 genes related to carbohydrate transport and utilization, respectively. Growth on cellulose led to the up-regulation of 32 carbohydrate-active (CAZy), 61 sugar transport, 25 transcription factor and 234 C/HP genes. Some C/HPs were overproduced on cellulose or xylan, suggesting their involvement in polysaccharide conversion. A unique feature of the genome is enrichment with genes encoding multi-modular, multi-functional CAZy proteins organized into one large cluster, the products of which are proposed to act synergistically on different components of plant cell walls and to aid the ability of C. bescii to convert plant biomass. The high duplication of CAZy domains coupled with the ability to acquire foreign genes by LGT may have allowed the bacterium to rapidly adapt to changing plant biomass-rich environments

Re-examination of the Controversial Coexistence of Traumatic Brain Injury and Posttraumatic Stress Disorder: Misdiagnosis and Self-Report Measures

The coexistence of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) remains a controversial issue in the literature. To address this controversy, we focused primarily on the civilian-related literature of TBI and PTSD. Some investigators have argued that individuals who had been rendered unconscious or suffered amnesia due to a TBI are unable to develop PTSD because they would be unable to consciously experience the symptoms of fear, helplessness, and horror associated with the development of PTSD. Other investigators have reported that individuals who sustain TBI, regardless of its severity, can develop PTSD even in the context of prolonged unconsciousness. A careful review of the methodologies employed in these studies reveals that investigators who relied on clinical interviews of TBI patients to diagnose PTSD found little or no evidence of PTSD. In contrast, investigators who relied on PTSD questionnaires to diagnose PTSD found considerable evidence of PTSD. Further analysis revealed that many of the TBI patients who were initially diagnosed with PTSD according to self-report questionnaires did not meet the diagnostic criteria for PTSD upon completion of a clinical interview. In particular, patients with severe TBI were often misdiagnosed with PTSD. A number of investigators found that many of the severe TBI patients failed to follow the questionnaire instructions and erroneously endorsed PTSD symptoms because of their cognitive difficulties. Because PTSD questionnaires are not designed to discriminate between PTSD and TBI symptoms or determine whether a patient's responses are accurate or exaggerated, studies that rely on self-report questionnaires to evaluate PTSD in TBI patients are at risk of misdiagnosing PTSD. Further research should evaluate the degree to which misdiagnosis of PTSD occurs in individuals who have sustained mild TBI

Is (poly-) substance use associated with impaired inhibitory control? A mega-analysis controlling for confounders.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics