The overall psychotropic and nonpsychotropic prescription intensity among children with ASDs is characterized by broad regional variation, suggesting diverse provider responses to pharmacotherapeutic uncertainty. This variation highlights a need for more research, practice-based learning, and shared decision making with caregivers surrounding therapy for children with ASDs.

ObjectivesFrom the first description by Leo Kanner [1], autism has been an enigmatic neurobehavioral phenomenon. The new genetic/genomic technologies of the past decade have not been as productive as originally anticipated in unveiling the mysteries of autism. The specific etiology of the majority of cases of autism spectrum disorder (ASD) is unknown, although numerous genetic/genomic variants and alterations of diverse cellular functions have been reported. Prompted by this failure, we have investigated whether the metabolomics approach might yield results which could simultaneously lead to a blood-based screening/diagnostic test and to treatment options. Methods Plasma samples from a clinically well-defined cohort of 100 male individuals, ages 2-16+ years, with ASD and 32 age-matched typically developing (TD) controls were subjected to global metabolomic analysis. ResultsWe have identified more than 25 plasma metabolites among the approximately 650 metabolites analyzed, representing over 70 biochemical pathways, that can discriminate children with ASD as young as 2 years from children that are developing typically. The discriminating power was greatest in the 2-10 year age group and weaker in older age groups. The initial findings were validated in a second cohort of 83 children, males and females, ages 2-10 years, with ASD and 76 age and gender-matched TD children. The discriminant metabolites were associated with several key biochemical pathways suggestive of potential contributions of increased oxidative stress, mitochondrial dysfunction, inflammation and immune dysregulation in ASD. Further, targeted quantitative analysis of a subset of discriminating metabolites using tandem mass spectrometry provided a reliable laboratory method to detect children with ASD. Conclusion Metabolic profiling appears to be a robust technique to identify children with ASD ages 2-10 years and provides insights into the altered metabolic pathways in ASD, which could lead to treatment strategies. ObjectivesTo uncover novel traits associated with nicotine and alcohol use genetics, we performed a phenome-wide association study in a large multi-ethnic cohort. Methods We investigated 7,688 African-Americans (AFR), 1,133 Asian-Americans (ASN), 14,081 European-Americans (EUR), and 3,492 Hispanic-Americans (HISP) from the Women's Health Initiative, analyzing risk alleles located in the CHRNA5-CHRNA3 locus (rs8034191, rs1051730, rs12914385, rs2036527, and rs16969968) for nicotine-related traits and ADH1B (rs1229984 and rs2066702) and ALDH2 (rs671) for alcohol-related traits with respect to anthropometric characteristics, dietary habits, social status, psychological circumstances, reproductive history, health conditions, and nicotine-and alcohol-related traits. ResultsThe investigated loci resulted associated with novel traits: rs1229984 were associated with family income (p=4.1*10 −12 ), having a pet (p=6.5*10 −11 ), partner education (p=1.8*10 −10 ), "usually expect the best" (p=2.4*10 −7), "felt calm and peaceful" (p=2.6*10 ), and num...

WHAT'S KNOWN ON THIS SUBJECT: Prescribing patterns in the US pediatric population are changing but not uniformly. A detailed examination of prescription variation is needed to better understand pharmacotherapy of children and to inform future exploration of the causes and consequences of diverse practices. WHAT THIS STUDY ADDS:We examine pediatric pharmacotherapy and quantify payer type differences and small geographic area variation. Substantial payer-type differences and regional variations were found, likely reflecting local practice cultures. Variation was greatest for medications used in situations of diagnostic and therapeutic uncertainty. abstract BACKGROUND: Despite the frequency of pediatric prescribing little is known about practice differences across small geographic regions and payer type (Medicaid and commercial). OBJECTIVE:The goal of this research was to quantify variation in prescription drug use among northern New England children. METHODS:Northern New England, all-payer administrative data (2007)(2008)(2009)(2010) permitted study of prescriptions for 949 821 children ages 0 to 17 years (1.75 million person-years [PYs]; 54% Medicaid, 46% commercial). Age-and gender adjusted overall and drug group-specific prescription use was quantified according to payer type (Medicaid or commercial) and within payer type across 69 hospital service areas (HSAs). We measured prescription fills per PY (rate) and annual, mean percentage of the population with any drug group-specific fills (prevalence). RESULTS:Overall mean annual prescriptions per PY were 3.4 (commercial) and 5.5 (Medicaid). Generally, these payer type differences were smaller than HSA-level variation within payer type. HSA-level rates of attention-deficit/hyperactivity disorder drug use (5th-95th percentile) varied twofold in Medicaid and more than twofold in commercially insured children; HSA-level antidepressant use varied more than twofold within each payer type. Antacid use varied threefold across HSAs and was highest in infants where commercial use paradoxically exceeded Medicaid. Prevalence of drug use varied as much as rates across HSAs.CONCLUSIONS: Prescription use was higher among Medicaid-insured than commercially insured children. Regional variation generally exceeded payer type differences, especially for drugs used in situations of diagnostic and therapeutic uncertainty. Efforts should advance best pediatric prescribing discussions and shared decision-making.