Alpha-2 agonists for attention-deficit/hyperactivity disorder in youth: a systematic review and meta-analysis of monotherapy and add-on trials to stimulant therapy.

OBJECTIVE: To meta-analyze the efficacy and safety of α-2 agonists in pediatric attention-deficit/hyperactivity disorder (ADHD). METHOD: We searched MEDLINE, EMBASE, Cochrane Library, CINAHL, and PsycINFO until May 2013 for randomized trials comparing α-2 agonists with placebo in ADHD youth. Primary outcome was reduction in overall ADHD symptoms. Secondary outcomes included hyperactivity/impulsivity, inattentiveness, oppositional defiant disorder symptoms (ODD symptoms), all-cause discontinuation, specific-cause discontinuation, and adverse effects. Standardized mean differences (SMD), relative risk (RR), and number-needed-to-treat/number-needed-to-harm (NNT/NNH) were calculated. Data were analyzed separately in monotherapy and as add-on to psychostimulants. RESULTS: Altogether, 12 studies (N = 2,276) were included. Across 9 studies (n = 1,550), α-2 agonist monotherapy significantly reduced overall ADHD symptoms (SMD = -0.59, p < .00001), hyperactivity/impulsivity (SMD = -0.56, p < .00001), inattention (SMD = -0.57, p < .00001), and ODD symptoms (SMD = -0.44, p = .0004). Similarly, α-2 agonist add-on treatment (3 studies, n = 726) significantly reduced overall ADHD symptoms (SMD = -0.36, p < .0001), hyperactivity/impulsivity (SMD = -0.33, p < .0001), and inattention (SMD = -0.34, p < .0001), but effect sizes were lower than in monotherapy trials (p = .03-0.04). As monotherapy, α-2 agonists had lower all-cause (RR = 0.70, p = .01, NNT = 10) and inefficacy-related (RR = 0.39, p < .0001) discontinuations than did placebo; however, intolerability-related discontinuation was similar, despite significantly more common fatigue (NNH = 10), sedation (NNH = 17), and somnolence (NNH = 4) and significantly greater hypotensive (clonidine-IR), bradycardic (clonidine-IR), and QTc prolonging (guanfacine-XR) effects. Added to stimulants, α-2 agonists had all-cause and specific-cause discontinuations that were comparable to those of placebo, but somnolence (NNH = 10) was more common, and hypotensive and bradycardic effects (clonidine-XR and guanfacine-XR) were greater than with placebo. CONCLUSIONS: α-2 Agonist monotherapy and, possibly to a lesser extent, co-treatment, are significantly superior to placebo for overall, hyperactivity, and inattentive ADHD symptoms. Efficacy advantages need to be balanced against fatigue, somnolence/sedation, hypotension, bradycardia, and possibly QTc prolongation.

Efficacy and safety of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: results from a comprehensive meta-analysis and metaregression.

OBJECTIVE: To comprehensively evaluate the efficacy and safety of atomoxetine (ATX) in pediatric attention-deficit/hyperactivity disorder (ADHD). METHOD: Meta-analysis of all double-blind randomized controlled trials (DBRCTs) evaluating the efficacy and tolerability of ATX for ADHD. Pooled, random-effects analyses were conducted, calculating standardized mean difference (SMD), yielding effect sizes (ES), relative risk (RR), and number-needed-to-treat/harm (NNT/NNH).Moderator/mediator analyses were also conducted, including metaregression. RESULTS: Across 25 DBRCTs (56 treatment arms, N = 3,928), ATX outperformed placebo regarding overall ADHD symptoms (ES = -0.64, 95% confidence interval [CI] = -0.56 to -0.71, p < 0.0001), hyperactivity/impulsivity (ES = -0.67, CI = -0.53 to -0.81, p < 0.0001), and inattention (ES = -0.59, CI = -0.51 to -0.67, p < 0.0001). Altogether, 44.4% versus 21.4% of patients improved by ≥40% (NNT = 4), whereas 39.9% versus 65.9% improved by <25% (NNT = 4). Oppositional defiant disorder symptoms (ES = -0.33) and quality-of-life-related outcomes (ES = -0.48 to -0.25) improved somewhat less. A higher percentage of treatment-naïve patients moderated the efficacy of ATX for overall ADHD symptoms (p = 0.017). All-cause discontinuation with ATX was similar to that for placebo (p = 1.00), with lower discontinuation because of inefficacy (relative risk [RR] = 0.51, CI = 0.36-0.74, p < 0.0001, NNT = 34), but higher discontinuation because of adverse effects (AEs) (RR = 1.89, CI = 1.08-3.31, p = 0.03, NNH = 50) with ATX. At least 1 adverse effect (AE) (70.4% versus 56.1%, p < 0.01, NNH = 6) and ≥1 psychiatric AE (21.5% versus 7.4%, NNH = 7, p < 0.01) were more frequent with ATX, whereas serious AEs (1.5% versus 1.0%), aggression (7.5% versus 6.0%), and suicidal ideation (1.3% versus 0.9%) were not different from placebo. CONCLUSIONS: Short-term ATX treatment is safe and superior to placebo for overall ADHD symptoms and key secondary outcomes, with a medium ES. However, a relevant patient subgroup (40%) continues to have significant symptomatology, requiring additional clinical attention.

Energy-guided learning approach to compressive FD-OCT.

High quality, large size volumetric imaging of biological tissue with optical coherence tomography (OCT) requires large number and high density of scans, which results in large data acquisition volume. This may lead to corruption of the data with motion artifacts related to natural motion of biological tissue, and could potentially cause conflicts with the maximum permissible exposure of biological tissue to optical radiation. Therefore, OCT can benefit greatly from different approaches to sparse or compressive sampling of the data where the signal is recovered from its sub-Nyquist measurements. In this paper, a new energy-guided compressive sensing approach is proposed for improving the quality of images acquired with Fourier domain OCT (FD-OCT) and reconstructed from sparse data sets. The proposed algorithm learns an optimized sampling probability density function based on the energy distribution of the training data set, which is then used for sparse sampling instead of the commonly used uniformly random sampling. It was demonstrated that the proposed energy-guided learning approach to compressive FD-OCT of retina images requires 45% fewer samples in comparison with the conventional uniform compressive sensing (CS) approach while achieving similar reconstruction performance. This novel approach to sparse sampling has the potential to significantly reduce data acquisition while maintaining image quality.

Compressive fluorescence microscopy using saliency-guided sparse reconstruction ensemble fusion.

Compressive fluorescence microscopy has been proposed as a promising approach for fast acquisitions at sub-Nyquist sampling rates. Given that signal-to-noise ratio (SNR) is very important in the design of fluorescence microscopy systems, a new saliency-guided sparse reconstruction ensemble fusion system has been proposed for improving SNR in compressive fluorescence microscopy. This system produces an ensemble of sparse reconstructions using adaptively optimized probability density functions derived based on underlying saliency rather than the common uniform random sampling approach. The ensemble of sparse reconstructions are then fused together via ensemble expectation merging. Experimental results using real fluorescence microscopy data sets show that significantly improved SNR can be achieved when compared to existing compressive fluorescence microscopy approaches, with SNR increases of 16-9 dB within the noise range of 1.5%-10% standard deviation at the same compression rate.

Saliency-guided compressive fluorescence microscopy.

A novel saliency-guided approach is proposed for improving the acquisition speed of compressive fluorescence microscopy systems. By adaptively optimizing the sampling probability density based on regions of interest instead of the traditional unguided random sampling approach, the proposed saliency-guided compressive fluorescence microscopy approach can achieve high-quality microscopy images using less than half of the number of fluorescence microscopy data measurements required by existing compressive fluorescence microscopy systems to achieve the same level of quality.