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BackgroundProgressive supranuclear palsy is a neurodegenerative tauopathy manifesting clinically as a progressive akinetic-rigid syndrome. In this study, we sought to identify genetic variants influencing PSP susceptibility through a genome-wide association analysis of a cohort of well-characterized patients who had participated in the Neuroprotection and Natural History in Parkinson Plus Syndromes and Blood Brain Barrier in Parkinson Plus Syndromes studies.MethodsWe genotyped single-nucleotide polymorphisms in 283 PSP cases from the United Kingdom, Germany, and France and compared these with genotypes from 4472 controls. Copy number variants were identified from genotyping data.ResultsWe observed associations on chromosome 17 within or close to the MAPT gene and explored the genetic architecture at this locus. We confirmed the previously reported association of rs1768208 in the MOBP gene (P = 3.29 × 10-13 ) and rs1411478 in STX6 (P = 3.45 × 10-10 ). The population-attributable risk from the MAPT, MOBP, and STX6 single-nucleotide polymorphisms was found to be 0.37, 0.26, and 0.08, respectively. In addition, we found 2 instances of copy number variants spanning the MAPT gene in patients with PSP. These copy number variants include tau but few other genes within the chromosome 17 haplotype region, providing additional support for the direct pathogenicity of MAPT in PSP.ConclusionsClinicians should also be aware of MAPT duplication as a possible genetic cause of PSP, especially in patients presenting with young age at onset. © 2019 International Parkinson and Movement Disorder Society.

BackgroundProgressive supranuclear palsy (PSP) is a rare neurodegenerative disease for which the genetic contribution is incompletely understood.MethodsWe conducted a joint analysis of 5,523,934 imputed SNPs in two newly-genotyped progressive supranuclear palsy cohorts, primarily derived from two clinical trials (Allon davunetide and NNIPPS riluzole trials in PSP) and a previously published genome-wide association study (GWAS), in total comprising 1646 cases and 10,662 controls of European ancestry.ResultsWe identified 5 associated loci at a genome-wide significance threshold P

PURPOSE:Early intervention for adolescent substance use and mental health problems may mitigate potential harm. We examined patient outcomes from a pragmatic trial of two modalities of delivering screening, brief intervention, and referral to treatment (SBIRT) and usual care (UC) in pediatric primary care. METHODS:All clinic pediatricians (n = 52) were randomized to three arms: (1) pediatrician-only, in which pediatricians were trained to deliver SBIRT; (2) embedded behavioral clinician (BC), in which pediatricians were trained to refer eligible adolescents to a BC who administered SBIRT; and (3) UC. Using electronic health record data, changes in past year substance use and depression symptoms between the index visit and next screening visit were examined across treatment arms. RESULTS:Among patients who endorsed substance use and/or depression symptoms or were eligible for further assessments, brief interventions, and referrals based on clinician assessment at the index visit, 648 patients (mean age = 15.2 [standard deviation = 1.2]) were rescreened at a follow-up visit between 6 months and 2 years later. Among all patients, self-reported substance use rates did not differ over time or across arms, and depression symptoms increased over time. The embedded BC arm had lower odds of having depression symptoms at follow-up than the physician-only arm, and lower odds than the UC arm although not significant; we found no differences between the pediatrician-only and UC arms. CONCLUSIONS:The increase in depression symptoms over time highlights this population's vulnerability and the importance of developing appropriate interventions. An embedded BC in pediatric primary care trained in SBIRT may benefit patients with depression symptoms.

ImportanceEarly intervention for substance use is critical to improving adolescent outcomes. Studies have found promising results for Screening, Brief Intervention, and Referral to Treatment (SBIRT), but little research has examined implementation.ObjectiveTo compare SBIRT implementation in pediatric primary care among trained pediatricians, pediatricians working in coordination with embedded behavioral health care practitioners (BHCPs), and usual care (UC).Design, setting, and participantsThe study is a 2-year (November 1, 2011, through October 31, 2013), nonblinded, cluster randomized, hybrid implementation and effectiveness trial examining SBIRT implementation outcomes across 2 modalities of implementation and UC. Fifty-two pediatricians from a large general pediatrics clinic in an integrated health care system were randomized to 1 of 3 SBIRT implementation arms; patients aged 12 to 18 years were eligible.InterventionsTwo modes of SBIRT implementation, (1) pediatrician only (pediatricians trained to provide SBIRT) and (2) embedded BHCP (BHCP trained to provide SBIRT), and (3) UC.Main outcomes and measuresImplementation of SBIRT (primary outcome), which included assessments, brief interventions, and referrals to specialty substance use and mental health treatment.ResultsThe final sample included 1871 eligible patients among 47 pediatricians; health care professional characteristics did not differ across study arms. Patients in the pediatrician-only (adjusted odds ratio [AOR], 10.37; 95% CI, 5.45-19.74; P < .001) and the embedded BHCP (AOR, 18.09; 95% CI, 9.69-33.77; P < .001) arms had higher odds of receiving brief interventions compared with patients in the UC arm. Patients in the embedded BHCP arm were more likely to receive brief interventions compared with those in the pediatrician-only arm (AOR, 1.74; 95% CI, 1.31-2.31; P < .001). The embedded BHCP arm had lower odds of receiving a referral compared with the pediatrician-only (AOR, 0.58; 95% CI, 0.43-0.78; P < .001) and UC (AOR, 0.65; 95% CI, 0.48-0.89; P = .006) arms; odds of referrals did not differ between the pediatrician-only and UC arms.Conclusions and relevanceThe intervention arms had better screening, assessment, and brief intervention rates than the UC arm. Patients in the pediatrician-only and UC arms had higher odds of being referred to specialty treatment than those in the embedded BHCP arm, suggesting lingering barriers to having pediatricians fully address substance use in primary care. Findings also highlight age and ethnic groups less likely to receive these important services.Trial registrationClinicaltrials.gov Identifier: NCT02408952.