Artemisinin-based combination therapy for treating uncomplicated Plasmodium vivax malaria

Background Plasmodium vivax is an important cause of malaria in many parts of Asia and South America, and parasite resistance to the standard treatment (chloroquine) is now high in some parts of Oceania. This review aims to assess the current treatment options in the light of increasing chloroquine resistance. Objectives To compare artemisinin-based combination therapies (ACTs) with alternative antimalarial regimens for treating acute uncomplicated P. vivax malaria. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; and the metaRegister of Controlled Trials (mRCT) up to 28 March 2013 using “vivax” and “arte* OR dihydroarte*” as search terms. Selection criteria Randomized controlled trials comparing ACTs versus standard therapy, or comparing alternative ACTs, in adults and children with uncomplicated P. vivax malaria. Data collection and analysis Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We used recurrent parasitaemia prior to day 28 as a proxy for effective treatment of the blood stage parasite, and compared drug treatments using risk ratios (RR) and 95% confidence intervals (CIs). We used trials following patients for longer than 28 days to assess the duration of the post-treatment prophylactic effect of ACTs. We assessed the quality of the evidence using the GRADE approach. Main results We included 14 trials, that enrolled 2592 participants, and were all conducted in Asia and Oceania between 2002 and 2011. ACTs versus chloroquine ACTs clear parasites from the peripheral blood quicker than chloroquine monotherapy (parasitaemia after 24 hours of treatment: RR 0.42, 95% CI 0.36 to 0.50, four trials, 1652 participants, high quality evidence). In settings where chloroquine remains effective, ACTs are as effective as chloroquine at preventing recurrent parasitaemias before day 28 (RR 0.58, 95% CI 0.18 to 1.90, five trials, 1622 participants, high quality evidence). In four of these trials, recurrent parasitaemias before day 28 were very low following treatment with both chloroquine and ACTs. The fifth trial, from Thailand in 2011, found increased recurrent parasitaemias following treatment with chloroquine (9%), while they remained low following ACT (2%) (RR 0.25, 95% CI 0.09 to 0.66, one trial, 437 participants). ACT combinations with long half-lives probably also provide a longer prophylactic effect after treatment, with significantly fewer recurrent parasitaemias between day 28 and day 42 or day 63 (RR 0.57, 95% CI 0.40 to 0.82, three trials, 1066 participants, moderate quality evidence). One trial, from Cambodia, Thailand, India and Indonesia, gave additional primaquine to both treatment groups to reduce the risk of spontaneous relapses. Recurrent parasitaemias after day 28 were lower than seen in the trials that did not give primaquine, but the ACT still appeared to have an advantage (RR 0.27, 95% CI 0.08 to 0.94, one trial, 376 participants, low quality evidence). ACTs versus alternative ACTs In high transmission settings, dihydroartemisinin-piperaquine is probably superior to artemether-lumefantrine, artesunate plus sulphadoxine-pyrimethamine and artesunate plus amodiaquine at preventing recurrent parasitaemias before day 28 (RR 0.20, 95% CI 0.08 to 0.49, three trials, 334 participants, moderate quality evidence). Dihydroartemisinin-piperaquine may also have an improved post-treatment prophylactic effect lasting for up to six weeks, and this effect may be present even when primaquine is also given to achieve radical cure (RR 0.21, 95% CI 0.10 to 0.46, two trials, 179 participants, low quality evidence). The data available from low transmission settings is too limited to reliably assess the relative effectiveness of ACTs. Authors' conclusions ACTs appear at least equivalent to chloroquine at effectively treating the blood stage of P. vivax infection. Even in areas where chloroquine remains effective, this finding may allow for simplified protocols for treating all forms of malaria with ACTs. In areas where chloroquine no longer cures the infection, ACTs offer an effective alternative. Dihydroartemisinin-piperaquine is the most studied ACT. It may provide a longer period of post-treatment prophylaxis than artemether-lumefantrine or artesunate plus amodiaquine. This effect may be clinically important in high transmission settings whether primaquine is also given or not

Complexity Analysis of Spontaneous Brain Activity in Attention-Deficit/Hyperactivity Disorder: Diagnostic Implications

Background: Attention-deficit/hyperactivity disorder (ADHD) is defined as the most common neurobehavioral disorder of childhood, but an objective diagnostic test is not available yet to date. Neurophychological, neuroimaging, and neurophysiological research offer ample evidence of brain and behavioral dysfunctions in ADHD, but these findings have not been useful as a diagnostic test. Methods: Whole-head magnetoencephalographic recordings were obtained from 14 diagnosed ADHD patients and 14 healthy children during resting conditions. Lempel-Ziv complexity (LZC) values were obtained for each channel and child and averaged in five sensor groups: anterior, central, left lateral, right lateral, and posterior. Results: Lempel-Ziv complexity scores were significantly higher in control subjects, with the maximum value in anterior region. Combining age and anterior complexity values allowed the correct classification of ADHD patients and control subjects with a 93% sensitivity and 79% specificity. Control subjects showed an age-related monotonic increase of LZC scores in all sensor groups, while children with ADHD exhibited a nonsignificant tendency toward decreased LZC scores. The age-related divergence resulted in a 100% specificity in children older than 9 years. Conclusions: Results support the role of a frontal hypoactivity in the diagnosis of ADHD. Moreover, the age-related divergence of complexity scores between ADHD patients and control subjects might reflect distinctive developmental trajectories. This interpretation of our results is in agreement with recent investigations reporting a delay of cortical maturation in the prefrontal corte

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Cerebral glucose metabolism on positron emission tomography of children

Establishing the normative range of age-dependent fluorodeoxyglucose (FDG) uptake in the developing brain is necessary for understanding regional quantitative analysis of positron emission tomography (PET) brain images in children and also to provide functional information on brain development. We analyzed head sections of FDG PET/computed tomography (CT) images for 115 patients (5 months to 23 years) without central nervous system disease before treatment, as PET studies are not performed on healthy children owing to ethical considerations and the risk of radiation exposure. We investigated the changes in FDG uptake and established age-associated normative ranges of cerebral FDG. Head sections of FDG PET/CT images were registered to a population-based probabilistic atlas of human cortical structures. Gray matter of 56 brain structures was defined on normalized PET images according to the atlas. To avoid individual and experimental confounding factors, the relative standardized uptake value (SUV) over the cerebellum of each structure was calculated. Relative SUVs were analyzed by ANOVA and modeled using generalized estimating equalization analysis with false discovery rate control. Age and structure were significant factors affecting SUVs. Anatomic proximity had little effect on FDG uptake. Linear and quadratic developmental trajectories were observed on absolute and relative SUVs, respectively. An increase from posterior-to-anterior and superior-to-inferior pattern was observed in both absolute SUV increase rate and relative SUV peak age. The SUV of each structure was modeled with respect to age, and these models can serve as baselines for the quantitative analysis of cerebral FDG-PET images of children

Soliton Dynamics in Computational Anatomy

Computational anatomy (CA) has introduced the idea of anatomical structures being transformed by geodesic deformations on groups of diffeomorphisms. Among these geometric structures, landmarks and image outlines in CA are shown to be singular solutions of a partial differential equation that is called the geodesic EPDiff equation. A recently discovered momentum map for singular solutions of EPDiff yields their canonical Hamiltonian formulation, which in turn provides a complete parameterization of the landmarks by their canonical positions and momenta. The momentum map provides an isomorphism between landmarks (and outlines) for images and singular soliton solutions of the EPDiff equation. This isomorphism suggests a new dynamical paradigm for CA, as well as new data representation.Comment: published in NeuroImag

What is the link between synaesthesia and sound symbolism?

Sound symbolism is a property of certain words which have a direct link between their phonological form and their semantic meaning. In certain instances, sound symbolism can allow non-native speakers to understand the meanings of etymologically unfamiliar foreign words, although the mechanisms driving this are not well understood. We examined whether sound symbolism might be mediated by the same types of cross-modal processes that typify synaesthetic experiences. Synaesthesia is an inherited condition in which sensory or cognitive stimuli (e.g., sounds, words) cause additional, unusual cross-modal percepts (e.g., sounds trigger colours, words trigger tastes). Synaesthesia may be an exaggeration of normal cross-modal processing, and if so, there may be a link between synaesthesia and the type of cross-modality inherent in sound symbolism. To test this we predicted that synaesthetes would have superior understanding of unfamiliar (sound symbolic) foreign words. In our study, 19 grapheme-colour synaesthetes and 57 non-synaesthete controls were presented with 400 adjectives from 10 unfamiliar languages and were asked to guess the meaning of each word in a two-alternative forced-choice task. Both groups showed superior understanding compared to chance levels, but synaesthetes significantly outperformed controls. This heightened ability suggests that sound symbolism may rely on the types of cross-modal integration that drive synaesthetes' unusual experiences. It also suggests that synaesthesia endows or co-occurs with heightened multi-modal skills, and that this can arise in domains unrelated to the specific form of synaesthesia

Executive function and theory of mind as predictors of aggressive and prosocial behavior and peer acceptance in early childhood

Executive function (EF) and theory of mind (ToM) are related to children’s social interactions, such as aggression and prosocial behavior, as well as their peer acceptance. However, limited research has examined different forms of aggression and the moderating role of gender. This study investigated links between EF, ToM, physical and relational aggression, prosocial behavior and peer acceptance and explored whether these relations are gender specific. Children (N=106) between 46- and 80-months-old completed tasks assessing cool and hot EF and ToM. Teaching staff rated children’s aggression, prosocial behavior, and peer acceptance. EF and ToM predicted physical, but not relational, aggression. Poor inhibition and delay of gratification were uniquely associated with greater physical aggression. EF and ToM did not predict prosocial behavior or peer acceptance. Added to this, gender did not moderate the relation between either EF or ToM and social outcomes. The correlates of aggression may therefore differ across forms of aggression but not between genders in early childhood

The functional neuroanatomy of bipolar disorder:a consensus model

OBJECTIVES: Functional neuroimaging methods have proliferated in recent years, such that functional magnetic resonance imaging, in particular, is now widely used to study bipolar disorder. However, discrepant findings are common. A workgroup was organized by the Department of Psychiatry, University of Cincinnati (Cincinnati, OH, USA) to develop a consensus functional neuroanatomic model of bipolar I disorder based upon the participants' work as well as that of others. METHODS: Representatives from several leading bipolar disorder neuroimaging groups were organized to present an overview of their areas of expertise as well as focused reviews of existing data. The workgroup then developed a consensus model of the functional neuroanatomy of bipolar disorder based upon these data. RESULTS: Among the participants, a general consensus emerged that bipolar I disorder arises from abnormalities in the structure and function of key emotional control networks in the human brain. Namely, disruption in early development (e.g., white matter connectivity and prefrontal pruning) within brain networks that modulate emotional behavior leads to decreased connectivity among ventral prefrontal networks and limbic brain regions, especially the amygdala. This developmental failure to establish healthy ventral prefrontal-limbic modulation underlies the onset of mania and ultimately, with progressive changes throughout these networks over time and with affective episodes, a bipolar course of illness. CONCLUSIONS: This model provides a potential substrate to guide future investigations and areas needing additional focus are identified