Differences between children and adolescents in treatment response to atomoxetine and the correlation between health-related quality of life and Attention Deficit/Hyperactivity Disorder core symptoms: Meta-analysis of five atomoxetine trials

<p>Abstract</p> <p>Objectives</p> <p>To explore the influence of age on treatment responses to atomoxetine and to assess the relationship between core symptoms of attention deficit/hyperactivity disorder (ADHD) and health-related quality of life (HR-QoL) outcomes.</p> <p>Data Sources</p> <p>Data from five similar clinical trials of atomoxetine in the treatment of children and adolescents with ADHD were included in this meta-analysis.</p> <p>Study Selection</p> <p>Atomoxetine studies that used the ADHD Rating Scale (ADHD-RS) and the Child Health and Illness Profile Child Edition (CHIP-CE) as outcome measures were selected.</p> <p>Interventions</p> <p>Treatment with atomoxetine.</p> <p>Main Outcome Measures</p> <p>Treatment group differences (atomoxetine vs placebo) in terms of total score, domains, and subdomains of the CHIP-CE were compared across age groups, and correlations between ADHD-RS scores and CHIP-CE scores were calculated by age.</p> <p>Results</p> <p>Data of 794 subjects (611 children, 183 adolescents) were pooled. At baseline, adolescents showed significantly (p < 0.05) greater impairment compared with children in the Family Involvement, Satisfaction with Self, and Academic Performance subdomains of the CHIP-CE. Treatment effect of atomoxetine was significant in both age groups for the Risk Avoidance domain and its subdomains. There was a significant age-treatment interaction with greater efficacy seen in adolescents in both the Risk Avoidance domain and the Threats to Achievement subdomain. Correlations between ADHD-RS and CHIP-CE scores were generally low at baseline and moderate in change from baseline and were overall similar in adolescents and children.</p> <p>Conclusions</p> <p>Atomoxetine was effective in improving some aspects of HR-QoL in both age groups. Correlations between core symptoms of ADHD and HR-QoL were low to moderate.</p

Atomoxetine treatment and ADHD-related difficulties as assessed by adolescent patients, their parents and physicians

<p>Abstract</p> <p>Background</p> <p>The degree of ADHD-related difficulties – reflecting overall impairment, social functioning, and quality of life – may be perceived differently by adolescent patients, parents and physicians. The primary aim of this study was to investigate ADHD-related difficulties during atomoxetine treatment, as perceived by the three different raters. Secondary objectives focused on effectiveness and tolerability of atomoxetine treatment in a population of adolescent patients with ADHD.</p> <p>Methods</p> <p>Adolescents with ADHD, aged 12–17 years, received open-label atomoxetine (0.5–1.2 mg/kg/day) up to 24 weeks. ADHD-related difficulties at various times of the day were rated using the Global Impression of Perceived Difficulties (GIPD) instrument. Inter-rater agreement was analyzed using Cohen's Kappa with 95% confidence intervals (95% CI). ADHD-Rating Scale (ADHD-RS) and Clinical Global Impression Severity (GGI-S) scores were assessed by the investigator; and spontaneous adverse events, vital signs and laboratory parameters were collected for tolerability assessments.</p> <p>Results</p> <p>159 patients received atomoxetine. Patients' baseline mean GIPD total ratings were significantly lower than parents' and physicians' scores (12.5 [95%CI 11.6;13.5] vs. 17.2 [16.2;18.2] and 18.8 [17.8;19.8]). For all raters, GIPD scores significantly improved over time. Changes were greatest within the first two weeks. Kappa coefficients varied between 0.186 [0.112;0.259] and 0.662 [0.529;0.795], with strongest agreements between parent and physician assessments, and significant improvements of patient/physician agreements over time (based on 95% CIs). ADHD-RS and CGI-S scores significantly improved over the course of the study (based on 95% CIs). Tolerability results were consistent with earlier reports.</p> <p>Conclusion</p> <p>ADHD-related difficulties were perceived differently by the raters in this open-label trial, but consistently improved during atomoxetine treatment. The GIPD instrument appeared sensitive to treatment-related change. These primarily quantitative findings may guide future studies to more systematically investigate the clinical and practical relevance of the differences observed. Additionally, in order to further validate these results, placebo- and comparator-controlled trials are recommended as well as inclusion of healthy controls and other patient populations.</p> <p>Trial Registration</p> <p><b>Clinical Trial Registry</b>: ClinicalTrials.gov: NCT00191737</p

Change in the direct cost of treatment for children and adolescents with hyperkinetic disorder in Germany over a period of four years

Abstract Background In many developed countries, the treatment of hyperkinetic disorder (or ADHD) consumes a considerable amount of resources. The primary aim of this study was to determine change in the direct cost of treatment for children and adolescents with hyperkinetic disorder in Germany over time, and compare the cost with the cost of treatment for two physical disorders: epilepsy and asthma. Methods The German Federal Statistical Office provided data on the direct cost of treating hyperkinetic disorder, epilepsy and asthma in Germany for 2002, 2004, and 2006. The direct costs of treatment incurred by hyperkinetic disorder in these years were compared with those incurred by epilepsy and asthma. Results The total direct cost of treatment for the hyperkinetic disorder was € 177 million in 2002, € 234 million in 2004, and € 341 million in 2006. The largest proportion of the cost was incurred by the age group Conclusion The direct cost of treatment for hyperkinetic disorder in the age group < 15 years increased considerably between 2002 and 2006. Over the same period of time and for the same age group, expenditure for epilepsy and asthma was more or less constant. The increase in expenditure for the treatment of hyperkinetic disorder may be due to increasing demand for diagnostic and therapeutic services and improved availability of such services. The study is limited by the difficulty of obtaining consistent data on the direct cost of treatment for both physical and psychiatric disorders in Germany.</p

Psychometric properties of the quality of life scale Child Health and Illness Profile-Child Edition in a combined analysis of five atomoxetine trials

Our aim was to evaluate the psychometric properties of the generic quality of life (QoL) scale Child Health and Illness Profile-Child Edition (CHIP-CE) by means of a combined analysis of atomoxetine clinical trials in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Individual patient-level data from five clinical trials were included in the combined analysis. Psychometric properties of the CHIP-CE were explored in terms of internal consistency and structure. Patients (n = 794) aged between 6 and 15 years (mean 9.7) with mean baseline ADHD Rating Scale of 41.8 ± 8.04 were included. On average, 0.7 (SD 2.23) items were missing for the whole CHIP-CE. The internal consistency of the CHIP-CE assessed by Cronbach’s alpha was good for all sub-domains at baseline and at endpoint. Considerable ceiling effects were only observed for the “restricted activity” sub-domain. No considerable floor effects were seen. The factor analysis supported the 12-factor solution for the sub-domains, but not the 5-factor solution for the domains. Our analyses were based on a large sample of non-US patients which allowed the measurement of clear changes in QoL over time. The results support that the CHIP-CE scale is psychometrically robust over time in terms of internal consistency and structure

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models