Treatment response and remission in a double-blind, randomized, head-to-head study of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit hyperactivity disorder

The Author(s) 2014. This article is published with open access at Springerlink.com Objectives A secondary objective of this head-to-head study of lisdexamfetamine dimesylate (LDX) and ato-moxetine (ATX) was to assess treatment response rates in children and adolescents with attention-deficit hyperactiv-ity disorder (ADHD) and an inadequate response to methylphenidate (MPH). The primary efficacy and safety outcomes of the study, SPD489-317 (ClinicalTrials.gov NCT01106430), have been published previously. Methods In this 9-week, double-blind, active-controlled study, patients aged 6–17 years with a previous inadequate response to MPH were randomized (1:1) to dose-optimized LDX (30, 50 or 70 mg/day) or ATX (patients \70 kg: 0.5–1.2 mg/kg/day, not to exceed 1.4 mg/kg/day; patients C70 kg: 40, 80 or 100 mg/day). Treatment response was a secondary efficacy outcome and was predefined as a reduction from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score of at least 25, 30 or 50 %. Sustained response was predefined as a reduction from baseline in ADHD-RS-IV total score (C25, C30 or C50 %) or a Clinical Global Impressions (CGI)–Improvement (CGI–I) score of 1 or 2 throughout weeks 4–9. CGI– Severity (CGI–S) scores were also assessed, as an indicator of remission. Results A total of 267 patients were enrolled (LDX, n = 133; ATX, n = 134) and 200 completed the study (LDX, n = 99; ATX, n = 101). By week 9, significantly (p \ 0.01) greater proportions of patients receiving LDX than ATX met the response criteria of a reduction from baseline in ADHD-RS-IV total score of at least 25 % (90.5 vs. 76.7 %), 30 % (88.1 vs. 73.7 %) or 50 % (73.0 vs. 50.4 %). Sustained response rates were also signifi-cantly (p \ 0.05) higher among LDX-treated patient

Growth and Puberty in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

BACKGROUND: Stimulant medications for the treatment of attention-deficit/hyperactivity disorder have a history of safe and effective use; however, concerns exist that they may adversely affect growth trajectories in children and adolescents. OBJECTIVE: The objective of this study was to evaluate the longer-term effects of lisdexamfetamine dimesylate on weight, height, body mass index and pubertal development in children and adolescents with attention-deficit/hyperactivity disorder. METHODS: Children and adolescents aged 6-17 years with attention-deficit/hyperactivity disorder took open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) in this open-label 2-year safety and efficacy study. Safety evaluations included treatment-emergent adverse events, measurement of weight, height and body mass index, and self-reported pubertal status using Tanner staging. RESULTS: The safety analysis population comprised all enrolled participants (N = 314) and 191 (60.8%) completed the study. Weight decrease was reported as a treatment-emergent adverse event in 63 participants (20.1%) and two participants (0.6%) discontinued the study as a result of treatment-emergent adverse events of weight decrease. Growth retardation of moderate intensity was reported as a treatment-emergent adverse event for two participants. From baseline to the last on-treatment assessment, there were increases in mean weight of 2.1 kg (standard deviation 5.83) and height of 6.1 cm (standard deviation 4.90), and a body mass index decrease of 0.5 kg/m2 (standard deviation 1.72). Mean weight, height and body mass index z-scores decreased over the first 36 weeks of the study and then stabilised. Changes from baseline to the last on-treatment assessment in mean z-scores for weight, height and body mass index were significantly less than zero (- 0.51, - 0.24 and - 0.59, respectively; nominal p < 0.0001). The proportion of participants with a z-score of < - 1 ranged from 5.1% (baseline) to 22.1% (week 84) for weight, 8.2% (baseline) to 12.6% (week 96) for height, and 8.3% (baseline) to 28.8% (week 96) for body mass index. Thirteen participants (4.1%) shifted to a weight below the fifth percentile at the last on-treatment assessment from a higher weight category at baseline. At the last on-treatment assessment, most participants remained at their baseline Tanner stage or had shifted higher. CONCLUSIONS: Findings from this comprehensive examination of growth outcomes associated with lisdexamfetamine dimesylate treatment over 2 years were consistent with previous studies of stimulant medications. Whilst mean weight and height increased over the course of the study, there was a small but transient reduction in mean weight, height and body mass index z-scores. A small increase in the proportion of participants in the lowest weight and body mass index categories highlights the importance of the regular monitoring of weight and height. There was no evidence of delayed onset of puberty. CLINICALTRIALS. GOV IDENTIFIER: NCT01328756

Prioritization of fish communities with a view to conservation and restoration on a large scale European basin, the Loire (France)

The hierarchical organization of important sites for the conservation or the restoration of fish communities is a great challenge for managers, especially because of financial or time constraints. In this perspective, we developed a methodology, which is easy to implement in different locations. Based on the fish assemblage characteristics of the Loire basin (France), we created a synthetic conservation value index including the rarity, the conservation status and the species origin. The relationship between this new synthetic index and the Fish-Based Index allowed us to establish a classification protocol of the sites along the Loire including fish assemblages to be restored or conserved. Sites presenting disturbed fish assemblages, a low rarity index, few threatened species, and a high proportion of non-native species were considered as important for the restoration of fish biodiversity. These sites were found mainly in areas where the assemblages are typical of the bream zone, e.g. with a higher number of eurytopic and limnophilic species. On the contrary, important sites for conservation were defined as having an important conservation potential (high RI, a lot of threatened species, and few nonnatives fish species) and an undisturbed fish assemblage similar to the expected community if habitats are undisturbed. Important sites for conservation were found in the Loire basin’s medium reaches which host assemblages typical for the grayling and the barbell zones, e.g. with a higher number of rheophilic species. The synthetic conservation value index could be adapted and completed with other criteria according to management priorities and capacities

Long-term effects of high-fat or high-carbohydrate diets on glucose tolerance in mice with heterozygous carnitine palmitoyltransferase-1a deficiency

Background: Abnormal fatty acid metabolism is an important feature in the mechanisms of insulin resistance and β-cell dysfunction. Carnitine palmitoyltransferase-1a (CPT-1a, liver isoform) has a pivotal role in the regulation of mitochondrial fatty acid oxidation. We investigated the role of CPT-1a in the development of impaired glucose tolerance using a mouse model for CPT-1a deficiency when challenged by either a high-carbohydrate (HCD) or a high-fat diet (HFD) for a total duration of up to 46 weeks

A Situational Alignment Framework for PACS

This paper reports the outcomes of a study on an integrated situational alignment framework for picture archiving and communication systems (PACS) labeled as PISA. Following the design research cycle, complementary validation methods and pilot cases were used to assess the proposed framework and its operationalized survey. In this paper, the authors outline (a) the process of the framework’ development, (b) the validation process with its underlying iterative steps, (c) the outcomes of pilot cases, and (d) improvement opportunities to refine and further validate the PISA framework. Results of this study support empirical application of the framework to hospital enterprises in order to gain insights into their PACS maturity and alignment. We argue that the framework can be applied as a valuable tool for assessments, monitoring and benchmarking purposes and strategic PACS planning

Organic Geochemical Studies. I. Molecular Criteria for Hydrocarbon Genesis

In recent years the search for life-forms at the earliest periods of geological time has been continued not only at the morphological level but also at the molecular level. This has been possible as a result of the increase in the biochemical knowledge and with the advent of analytical techniques that are capable of describing the intimate molecular architecture of individual molecules in acute detail. The fundamental premises upon which this organic geochemical approach rest are the following: that certain molecules, possessing a characteristic structural skeleton, show a reasonable stability to degradation over long periods of geological time; that their structural specificity can be understood in terms of known biosynthetic sequences; and that their formation by any non-biological means is of negligible probability. In this manuscript it is proposed to critically re-examine these premises and to establish criteria whereby one can differentiate molecules derived from biological systems from those that have their origin in non-biological processes. The importance of establishing such criteria lies in the significance these criteria have in determining whether life exists, or has existed, on other planets. Within the very near future it may be possible to provide an initial answer to this question when the first lunar samples are returned to the earth for analysis

Stromal Cell-Derived Factor 1 Polymorphism in Retinal Vein Occlusion

BACKGROUND: Stromal cell-derived factor 1 (SDF1) has crucial role in the regulation of angiogenesis and ocular neovascularisation (NV). The purpose of this study was to evaluate the association between SDF1-3'G(801)A polymorphism and NV complications of retinal vein occlusion (RVO). METHODS: 130 patients with RVO (median age: 69.0, range 35-93 years; male/female- 58/72; 55 patients had central RVO, 75 patients had branch RVO) were enrolled in this study. In the RVO group, 40 (30.8%) patients were diagnosed with NV complications of RVO and 90 (69.2%) patients without NVs. The median follow up period was 40.3 months (range: 18-57 months). The SDF1-3'G(801)A polymorphism was detected by PCR-RFLP. Allelic prevalence was related to reference values obtained in the control group consisted of 125 randomly selected, age and gender matched, unrelated volunteers (median age: 68.0, range 36-95 years; male/female- 53/72). Statistical analysis of the allele and genotype differences between groups (RVO patients vs controls; RVO patients with NV vs RVO patients without NV) was determined by chi-squared test. P value of <0.05 was considered statistically significant. RESULTS: Hardy-Weinberg criteria was fulfilled in all groups. The SDF1-3'G(801)A allele and genotype frequencies of RVO patients were similar to controls (SDF1-3'A allele: 22.3% vs 20.8%; SDF1-3'(801)AA: 5.4% vs 4.8%, SDF1-3'(801)GG: 60.8% vs 63.2%). The frequency of SDF1-3'(801)AA and SDF1-3'(801)GA genotypes, as well as the SDF1-3'(801)A allele frequency were higher in RVO patients with NV versus in patients without NV complication (SDF1-3'(801)AA+AG genotypes: 57.5% vs 31.1%, p = 0.008; SDF1-3'(801)A allele: 35.0% vs 16.7%, p = 0.002) or versus controls (SDF1-3'(801)AA+AG genotypes 57.5% vs 36.8%, p = 0.021; SDF1-3'(801)A allele: 35.0% vs 20.8% p = 0.01). Carrying of SDF1-3'(801)A allele increased the risk of neovascularisation complications of RVO by 2.69 (OR, 95% CI = 1.47-4.93). CONCLUSION: These findings suggest that carrying SDF1-3'(801)A allele plays a role in the development of neovascular complications in retinal vein occlusion

Dissociated Representations of Pleasant and Unpleasant Olfacto-Trigeminal Mixtures: An fMRI Study

How the pleasantness of chemosensory stimuli such as odorants or intranasal trigeminal compounds is processed in the human brain has been the focus of considerable recent interest. Yet, so far, only the unimodal form of this hedonic processing has been explored, and not its bimodal form during crossmodal integration of olfactory and trigeminal stimuli. The main purpose of the present study was to investigate this question. To this end, functional magnetic resonance imaging (fMRI) was used in an experiment comparing brain activation related to a pleasant and a relatively unpleasant olfacto-trigeminal mixture, and to their individual components (CO2 alone, Orange alone, Rose alone). Results revealed first common neural activity patterns in response to both mixtures in a number of regions: notably the superior temporal gyrus and the caudate nucleus. Common activations were also observed in the insula, although the pleasant mixture activated the right insula whereas the unpleasant mixture activated the left insula. However, specific activations were observed in anterior cingulate gyrus and the ventral tegmental area only during the perception of the pleasant mixture. These findings emphasized for the firs time the involvement of the latter structures in processing of pleasantness during crossmodal integration of chemosensory stimuli

Do Fleas Affect Energy Expenditure of Their Free-Living Hosts?

Parasites can cause energetically costly behavioural and immunological responses which potentially can reduce host fitness. However, although most laboratory studies indicate that the metabolic rate of the host increases with parasite infestation, this has never been shown in free-living host populations. In fact, studies thus far have shown no effect of parasitism on field metabolic rate (FMR).We tested the effect of parasites on the energy expenditure of a host by measuring FMR using doubly-labelled water in free-living Baluchistan gerbils (Gerbillus nanus) infested by naturally occurring fleas during winter, spring and summer. We showed for the first time that FMR of free-living G. nanus was significantly and positively correlated with parasite load in spring when parasite load was highest; this relationship approached significance in summer when parasite load was lowest but was insignificant in winter. Among seasons, winter FMRs were highest and summer FMRs were lowest in G. nanus.The lack of parasite effect on FMR in winter could be related to the fact that FMR rates were highest among seasons. In this season, thermoregulatory costs are high which may indicate that less energy could be allocated to defend against parasites or to compensate for other costly activities. The question about the cost of parasitism in nature is now one of the major themes in ecological physiology. Our study supports the hypothesis that parasites can elevate FMR of their hosts, at least under certain conditions. However, the effect is complex and factors such as season and parasite load are involved

Identification of Behaviour in Freely Moving Dogs (Canis familiaris) Using Inertial Sensors

Monitoring and describing the physical movements and body postures of animals is one of the most fundamental tasks of ethology. The more precise the observations are the more sophisticated the interpretations can be about the biology of a certain individual or species. Animal-borne data loggers have recently contributed much to the collection of motion-data from individuals, however, the problem of translating these measurements to distinct behavioural categories to create an ethogram is not overcome yet. The objective of the present study was to develop a “behaviour tracker”: a system composed of a multiple sensor data-logger device (with a tri-axial accelerometer and a tri-axial gyroscope) and a supervised learning algorithm as means of automated identification of the behaviour of freely moving dogs. We collected parallel sensor measurements and video recordings of each of our subjects (Belgian Malinois, N=12; Labrador Retrievers, N=12) that were guided through a predetermined series of standard activities. Seven behavioural categories (lay, sit, stand, walk, trot, gallop, canter) were pre-defined and each video recording was tagged accordingly. Evaluation of the measurements was performed by support vector machine (SVM) classification. During the analysis we used different combinations of independent measurements for training and validation (belonging to the same or different individuals or using different training data size) to determine the robustness of the application. We reached an overall accuracy of above 90% perfect identification of all the defined seven categories of behaviour when both training and validation data belonged to the same individual, and over 80% perfect recognition rate using a generalized training data set of multiple subjects. Our results indicate that the present method provides a good model for an easily applicable, fast, automatic behaviour classification system that can be trained with arbitrary motion patterns and potentially be applied to a wide range of species and situations