Attention deficit hyperactivity disorder (ADHD) is a common and persistent condition characterized by developmentally atypical and impairing inattention, hyperactivity, and impulsiveness. We identified de novo and rare copy number variations (CNVs) in 248 unrelated ADHD patients using million-feature genotyping arrays. We found de novo CNVs in 3 of 173 (1.7%) ADHD patients for whom we had DNA from both parents. These CNVs affected brain-expressed genes: DCLK2, SORCS1, SORCS3, and MACROD2. We also detected rare inherited CNVs in 19 of 248 (7.7%) ADHD probands, which were absent in 2357 controls and which either overlapped previously implicated ADHD loci (for example, DRD5 and 15q13 microduplication) or identified new candidate susceptibility genes (ASTN2, CPLX2, ZBBX, and PTPRN2). Among these de novo and rare inherited CNVs, there were also examples of genes (ASTN2, GABRG1, and CNTN5) previously implicated by rare CNVs in other neurodevelopmental conditions including autism spectrum disorder (ASD). To further explore the overlap of risks in ADHD and ASD, we used the same microarrays to test for rare CNVs in an independent, newly collected cohort of 349 unrelated individuals with a primary diagnosis of ASD. Deletions of the neuronal ASTN2 and the ASTN2-intronic TRIM32 genes yielded the strongest association with ADHD and ASD, but numerous other shared candidate genes (such as CHCHD3, MACROD2, and the 16p11.2 region) were also revealed. Our results provide support for a role for rare CNVs in ADHD risk and reinforce evidence for the existence of common underlying susceptibility genes for ADHD, ASD, and other neuropsychiatric disorders.

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Background Potentially harmful errors occur in pediatric patients at a rate three times higher than in adults, mainly due to dosage calculations. Objective. To evaluate the effect of Computerized Prescription Order Entry (CPOE) and Decision Support Systems (DSS) on Adverse Drug Events (ADE) in pediatrics. Method. Systematic review updated up to December 2019 in the PubMed, Scopus, Web of Science and Embase, Lilacs and cross-references, recorded in Prospero CRD 42019126590. Observational and pre- and post-implementation CPOE studies were included. in any language. A scale was used for methodological evaluation of the studies. Relative risk (RR), attributable risk (AR) or number needed to treat (NNT) with 95% CIs were computed for comparing the incidence of total, actual, preventable and potentially harmful ADE. Results Starting with 203 retrieved abstracts, 12 articles were included - eight interventional and four observational studies. Five articles evaluated CPOE and seven CPOE plus DSS. Settings for eleven studies were hospitals and one an outpatient facility. Sample sizes ranged from 514 to 45,615 totaling 112,187 patients. The number of prescriptions ranged from 724 to 92,398, totaling 182,803. A reduction in total ADE was observed in two studies. The risk reduction of preventable ADE ranged from 24% RR 0.76 (0.59 - 0.97) to 47% RR 0.53 (0.29-0.91) in four articles. Potentially harmful ADE (ADE ph) in five studies were reduced from 76% RR = 0.24 (0.09-0.68) to 44% (RR 0.56 (0.46 - 0.70), with an AR variyng from 1.8 to 0.9%. One of the articles stated that 64 (95% CI 25-100) patients would need to be using CPOE in order to avoid one potentially harmful ADE. Studies identified reductions in ADE in various settings- two in wards, one in wards and Pediatric Intensive Care Unit (PICU), the others in PICU and Neonatal Intensive Care Units. Conclusions Implementation of CPOE plus DSS reduces EADs in pediatric settings. Key messages Accumulated evidence favors implementation of CPOE plus DSS as important for prevention of ADE in pediatric settings. Potentially harmful and preventable errors can be avoided by implementing electronic prescribing systems in pediatrics. Its use should be encouraged in countries in low-income countries.