Transcutaneous electrical acupoint stimulation for children with attention-deficit/hyperactivity disorder : a randomized clinical trial

Little is known about the effects of transcutaneous electrical acupoint stimulation (TEAS) for children with attention-deficit/ hyperactivity disorder (ADHD). Here, we carried out a 4 week randomized clinical trial in which patients aged 6–12 years old with an ADHD diagnosis received TEAS or sham TEAS. The primary outcome measure was the investigator-rated Clinical Global Impression-Improvement (CGI-I) score at week 4. Secondary outcomes included changes from baseline to week 4 in the investigator-rated Clinical Global Impression-Severity of Illness (CGI-S) score, the Conners’ Parent/Teacher Rating Scales-Revised: Short Form (CPRS-R: S/CTRS-R: S) score, go/no-go task performance, and functional near-infrared spectroscopy (fNIRS)-based oxygenated hemoglobin level within the prefrontal cortex. At week 4, the CGI-I score indicated improvement in 33.3% of the TEAS group compared with 7.7% of the sham group (P = 0.005). The TEAS group had a greater decrease in the mean CGI-S score (−0.87) than the sham TEAS group (−0.28) (P = 0.003). A greater enhancement in the mean cerebral oxygenated hemoglobin within the prefrontal cortex was found in the TEAS group (0.099 mM mm) compared with the sham TEAS group (0.005 mM mm) (P < 0.001). CPRS-R: S score, CTRS-R: S score, and go/no-go performance exhibited no significant improvement after TEAS treatment. The manipulation-associated adverse events were uncommon in both groups, and events were very mild. Our results show that noninvasive TEAS significantly improved general symptoms and increased prefrontal cortex blood flow within 4 weeks for children with ADHD. Further clinical trials are required to understand the long-term efficacy in a larger clinical sample. This trial was registered on ClinicalTrials.gov (NCT 03917953)

208 evidence-based conclusions about the disorder

Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma

Phenotypic and measurement influences on heritability estimates in childhood ADHD

Twin studies described a strongly heritable component of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. However, findings varied considerably between studies. In addition, ADHD presents with a high rate of comorbid disorders and associated psychopathology. Therefore, this literature review reports findings from population-based twin studies regarding the influence of subtypes, assessment instruments, rater effects, sex differences, and comorbidity rates on ADHD heritability estimates. In addition, genetic effects on the persistence of ADHD are discussed. By reviewing relevant factors influencing heritability estimates more homogeneous subtypes relevant for molecular genetic studies can be elicited. A systematic search of population-based twin studies in ADHD was performed, using the databases PubMed and PsycInfo. Results of family studies were added in case insufficient or contradictory findings were obtained in twin studies. Heritability estimates were strongly influenced by rater effects and assessment instruments. Inattentive and hyperactive–impulsive symptoms were likely influenced by common as well as specific genetic risk factors. Besides persistent ADHD, ADHD accompanied by symptoms of conduct or antisocial personality disorder might be another strongly genetically determined subtype, however, family environmental risk factors have also been established for this pattern of comorbidity

Teaching facts of addition to Brazilian children with attention-deficit/hyperactivity disorder

Storage and/or automatic retrieval of the basic facts of addition from the long-term memory seems to be impaired in children with ADHD presenting arithmetical difficulties. The present study was carried out to evaluate the effectiveness of an educational intervention model designed to teach basic facts of addition as a means of advancing from counting procedures to memory-based processes in 7 children with ADHD, divided into two groups (control and intervention). The main hypothesis was that the explicit teaching of decomposition strategies would lead to an advanced use of a memory-based procedure. It is an experimental study involving the use of a blind, parallel, randomized, controlled clinical trial. The intervention group participated in 10 one-hour sessions over a 10-week period, while the control group received the same quantity and distribution of teaching time. They carried out the kind of activities generally carried out in the classroom. Although there was no apparent statistical difference between the groups, our findings suggest that the tested educational intervention model is effective at promoting the retrieval of memory-based facts, since the intervention group came to predominantly adopt a memory-based strategy. A carefully designed educational program enhances memory-based processes in students with ADHD. These findings have important implications for further research considering interventions for both students with ADHD and those who perform poorly in arithmetic

Post-myocardial infarction ventricular remodeling : basic concepts and emerging perspectives

Remodelamento ventricular se refere ao processo fisiopatológico caracterizado por alterações da morfologia ventricular e que, freqüentemente, culmina em dilatação das cavidades cardíacas. O processo de dilatação ventricular pós-infarto ocorre após um dano isquêmico agudo e irreversível, sendo influenciado primordialmente por três fatores interdependentes: o tamanho do infarto, o estresse da parede ventricular e o processo de cicatrização tecidual. Os meios mais eficientes de evitar ou minimizar o aumento nas dimensões ventriculares após um infarto são através da limitação do dano isquêmico e da redução da pós-carga e da tensão da parede ventricular. Recentemente, o papel da síntese e degradação da matriz extracelular nos processos relacionados com o remodelamento ventricular pós-infarto vem recebendo grande interesse. A modulação da atividade de uma família de enzimas proteolíticas, as metaloproteinases, responsáveis pela degradação de proteínas da matriz extracelular, emergiu como uma estratégia terapêutica potencial para pacientes em risco de desenvolver quadros de falência miocárdica. Dados promissores, utilizando modelos de infarto experimental, sugerem que esse tipo de abordagem poderá ter um papel relevante no tratamento do remodelamento ventricular pósinfarto De forma similar, diversos investigadores têm avaliado estratégias inovadoras de tratamento que se baseiam no conceito de que a regeneração do tecido miocárdico é factível e segura, envolvendo o uso de terapias com células pluripotentes. Inúmeros estudos experimentais já avaliaram o uso destas células em diferentes modelos de lesão miocárdica, demonstrando resultados consistentemente benéficos em aspectos funcionais. Estudos clínicos estão sendo desenvolvidos em todo o mundo, incluindo iniciativas no Brasil, para definir o papel destas estratégias de tratamento na reversão do remodelamento ventricular pós-infarto.Postinfarction ventricular remodeling is a pathophysiological process characterized by changes in ventricular geometry and frequently leading to progressive chamber dilatation. The process of postinfarction ventricular dilatation, which is a result of an acute and irreversible ischemic injury, is mainly influenced by three interdependent factors: infarct size, ventricular wall stress and the tissue healing process. The most efficient strategies in order to avoid or minimize increases in ventricular dimension after an infarction involve attempts to limit the ischemic damage and afterload and ventricular wall stress reduction. The role of the synthesis and degradation of the extracellular matrix in processes related to the postinfarction ventricular remodeling has recently received increasing interest. Modulation of the activity of several proteolytic enzymes - the metalloproteinases, which are responsible for the degradation of the extracellular matrix - has emerged as a potential therapeutic strategy for patients at risk of developing heart failure. Preliminary experimental data on animal models suggest that this approach may have a relevant role in the management of postinfarction ventricular remodeling. Similarly, several investigators have evaluated innovative treatment strategies based on the concept that the myocardial tissue regeneration using pluripotent cells is feasible and safe. Several experimental studies have shown that the use of pluripotent cells in different models of myocardial damage results in significant improvement in functional outcomes. Clinical studies that are being developed worldwide, including in Brazil, will define the role of such strategies to reverse postinfarction ventricular remodeling

Decline in attention-deficit hyperactivity disorder traits over the life course in the general population : trajectories across five population birth cohorts spanning ages 3 to 45 years

Background Trajectories of attention-deficit hyperactivity disorder (ADHD) traits spanning early childhood to mid-life have not been described in general populations across different geographical contexts. Population trajectories are crucial to better understanding typical developmental patterns. Methods We combined repeated assessments of ADHD traits from five population-based cohorts, spanning ages 3 to 45 years. We used two measures: (i) the Strengths and Difficulties Questionnaire (SDQ) hyperactive-inattentive subscale (175 831 observations, 29 519 individuals); and (ii) scores from DSM-referenced scales (118 144 observations, 28 685 individuals). Multilevel linear spline models allowed for non-linear change over time and differences between cohorts and raters (parent/teacher/self). Results Patterns of age-related change differed by measure, cohort and country: overall, SDQ scores decreased with age, most rapidly declining before age 8 years (-0.157, 95% CI: -0.170, -0.144 per year). The pattern was generally consistent using DSM scores, although with greater between-cohort variation. DSM scores decreased most rapidly between ages 14 and 17 years (-1.32%, 95% CI: -1.471, -1.170 per year). Average scores were consistently lower for females than males (SDQ: -0.818, 95% CI: -0.856, -0.780; DSM: -4.934%, 95% CI: -5.378, -4.489). This sex difference decreased over age for both measures, due to an overall steeper decrease for males. Conclusions ADHD trait scores declined from childhood to mid-life, with marked variation between cohorts. Our results highlight the importance of taking a developmental perspective when considering typical population traits. When interpreting changes in clinical cohorts, it is important to consider the pattern of expected change within the general population, which is influenced by cultural context and measurement

Abnormal Brain Connectivity Patterns in Adults with ADHD: A Coherence Study

Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach - unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. the median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. in addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Institute of Mental HealthNovartisJanssen-CilagAbbottEli-LillyShireBristol-Myers SquibbUniv Fed ABC, Ctr Math Computat & Cognit, Santo Andre, BrazilUniversidade Federal de São Paulo, Lab Interdisciplinar Neurociencias Clin, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilHosp Clin Porto Alegre, Child & Adolescent Psychiat Div, ADHD Outpatient Program, Porto Alegre, RS, BrazilNYU, Ctr Child Study, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY USAInst Nacl Psiquiatria Desenvolvimento, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Lab Interdisciplinar Neurociencias Clin, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilNational Institute of Mental Health: R01MH083246Web of Scienc

Lean back and wait for the alarm? Testing an automated alarm system for nosocomial outbreaks to provide support for infection control professionals

INTRODUCTION: Outbreaks of communicable diseases in hospitals need to be quickly detected in order to enable immediate control. The increasing digitalization of hospital data processing offers potential solutions for automated outbreak detection systems (AODS). Our goal was to assess a newly developed AODS. METHODS: Our AODS was based on the diagnostic results of routine clinical microbiological examinations. The system prospectively counted detections per bacterial pathogen over time for the years 2016 and 2017. The baseline data covers data from 2013-2015. The comparative analysis was based on six different mathematical algorithms (normal/Poisson and score prediction intervals, the early aberration reporting system, negative binomial CUSUMs, and the Farrington algorithm). The clusters automatically detected were then compared with the results of our manual outbreak detection system. RESULTS: During the analysis period, 14 different hospital outbreaks were detected as a result of conventional manual outbreak detection. Based on the pathogens' overall incidence, outbreaks were divided into two categories: outbreaks with rarely detected pathogens (sporadic) and outbreaks with often detected pathogens (endemic). For outbreaks with sporadic pathogens, the detection rate of our AODS ranged from 83% to 100%. Every algorithm detected 6 of 7 outbreaks with a sporadic pathogen. The AODS identified outbreaks with an endemic pathogen were at a detection rate of 33% to 100%. For endemic pathogens, the results varied based on the epidemiological characteristics of each outbreak and pathogen. CONCLUSION: AODS for hospitals based on routine microbiological data is feasible and can provide relevant benefits for infection control teams. It offers in-time automated notification of suspected pathogen clusters especially for sporadically occurring pathogens. However, outbreaks of endemically detected pathogens need further individual pathogen-specific and setting-specific adjustments

O tratamento farmacológico do transtorno bipolar na infância e adolescência

Juvenile Bipolar Disorder (JBD) has been recognized more frequently in the last years. The disorder might have an atypical presentation in this age range. Thus, irritability with "affective storms" are more frequent than euphoria, the evolution of the disorder is more chronic than episodic and mixed symptoms are more frequent. High prevalence of comorbid conditions, specially Attention-Deficit/Hyperactivity Disorder, seems to be the rule. Despite the devastating effect of JBD in the child development, few pharmacological investigations were conducted in these patients. This review aims to present a critical discussion of the findings from this emerging new area of research, the psychopharmacology of the JBD. To accomplish this task, a systematic computerized search of the literature was conducted through the PUBMED. Findings are presented in three sections: 1) the strength of the scientific evidence in the field; 2) critical description of the main investigations; 3) proposition of an algorithm to guide treatment options. Only one randomized, double-blind, controlled trial was found in the literature. Almost all studies are open prospective trials, case series, or retrospective analyses of medical records. The most investigated drugs are lithium and valproate sodium. This review suggest that a scarce availability of high quality evidence to guide clinicians in the decision on which pharmacological treatment should be used to address bipolar disorder in children and adolescents.O reconhecimento do transtorno do humor bipolar (THB) em crianças e adolescentes tem aumentado significativamente nos últimos anos. O THB, nessa faixa etária, parece freqüentemente se apresentar de forma atípica, assim, humor irritável com "tempestades afetivas" são mais freqüentes do que euforia, o curso da doença é mais crônico do que episódico e sintomas mistos com depressão e mania concomitantes são comuns. Alta prevalência de comorbidades, em especial com transtorno do déficit de atenção/hiperatividade, parece ser a regra. Apesar do efeito devastador do THB no desenvolvimento infantil, poucos estudos têm investigado intervenções farmacológicas nesses pacientes. Essa revisão tem como objetivo apresentar uma discussão crítica dos achados provenientes de estudos recentes nessa nova área de pesquisa, a psicofarmacologia do THB em crianças e adolescentes. Para realizar essa tarefa, uma revisão computadorizada e sistemática da literatura foi realizada por meio do PUBMED. Os dados sobre tratamento psicofarmacológico do THB em crianças e adolescentes são apresentados em três seções: 1) a força da evidência científica na área; 2) descrição crítica dos estudos principais; 3) proposição de um algoritmo de decisão. Apenas um estudo randomizado duplo-cego e controlado por placebo foi encontrado. A quase totalidade dos estudos é composta de ensaios prospectivos abertos, séries de casos e análises retrospectivas de prontuários. Os fármacos mais estudados são o lítio e o valproato de sódio. Essa revisão indica uma escassa disponibilidade de evidência científica de qualidade para guiar o clínico na decisão do tratamento farmacológico a ser indicado para o THB em crianças e adolescentes