The Utility of Pharmacogenetic-Guided Psychotropic Medication Selection for Pediatric Patients: A Retrospective Study.

BACKGROUND: To describe trends and clinical experiences in applying commercial pharmacogenetic testing among pediatric patients with neuropsychiatric disorders. METHODS: Demographic and clinical data of patients receiving GeneSight® testing from January 2015 to November 2016 at an urban pediatric hospital were retrospectively extracted from medical charts. Outcome data included pharmacogenetic test results and medication prescriptions before and after the test. RESULTS: A total of 450 patients (12.1 ± 4.3 years) diagnosed with anxiety disorder, attention deficit hyperactivity disorder, developmental disorders including autism, and/or a mood disorder received testing, and 435 of them were prescribed medications. Comparing data before and after testing, the total number of psychotropic prescriptions were reduced by 27.2% and the number of prescribed medications with severe gene-drug interactions decreased from 165 to 95 (11.4% to 8.9% of total medications prescribed). Approximately 40% of actionable genetic annotation were related to CYP2CD6 and CYP2C19. Patients of Asian descent had significantly higher likelihood than other races of being classified as poor to intermediate metabolizers of antidepressants, mood stabilizers, and antipsychotics (p = 0.008, 0.007, and 0.001, respectively). Diagnoses, including autism spectrum disorder, were not associated with increased risks of severe gene-drug interactions. CONCLUSIONS: Pharmacogenetic testing in child and adolescent psychiatry is currently based on few clinically actionable genes validated by CPIC and/or FDA. Although this approach can be moderately utilized to guide psychotropic medication prescribing for pediatric patients with psychiatric disorders, clinicians should cautiously interpret test results while still relying on clinical experience and judgment to direct the final selection of medication.

Marijuana commercialization and adolescent substance treatment outcomes in Colorado.

BACKGROUND AND OBJECTIVES: In Colorado, marijuana was legalized for medical use in 2000, commercialized in 2009, and approved for recreational purposes in 2012. Little is known about the association between recent policy changes and adolescent substance treatment outcomes measured by urine drug screens (UDS). This study addressed this research gap. METHODS: Participants were youth (N = 523) aged 11-19 years who were enrolled in an outpatient motivational interviewing (MI)/cognitive behavioral therapy (CBT) plus contingency management (CM) in Denver, Colorado from October 2007 to June 2014. The measures included UDS collected during weekly treatment sessions and sent to a commercial laboratory for quantitative analysis of tetrahydrocannabinol (THC)/Creatinine (Cr). Linear regression models and logistic regression models using a Generalized Estimating Equations (GEE) approach for repeated measures were completed to answer the study aims. RESULTS: Males, but not females, had a marginally significant increasing trend over time in monthly average THC/Cr (ß = 1.99, p = 0.046). There was a significant increasing trend over time (per 30 days) in the odds of having a negative UDS within 6 sessions (OR = 1.02, 95%CI = 1.003-1.04, p = 0.006). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Based on these data, substance treatment outcomes from MI and CBT are mixed, but overall treatment appears to remain effective in a state with legalized marijuana. (Am J Addict 2017;26:802-806).

Practical Aspects of Discussing Marijuana in a New Era.

The use of marijuana for the treatment of medical conditions is a highly controversial topic. Misconceptions by both patients and providers concerning the safety of and evidence-based indications for marijuana can complicate treatment planning and outcomes. Maintaining skills such as motivational interviewing, providing evidence-based informed consent, and increasing access to care remain top priorities for providing quality patient care. The goal of this article is to offer guidance to clinical providers who are adapting to the changing realities of medical marijuana and legalized recreational marijuana.

Substance Abuse Prevention.

Substance use disorders account for approximately 6% of deaths worldwide and cost about $700 billion in the United States. Approximately 80% of drug users begin using during adolescence, underscoring the public health importance of effective substance prevention programs for youth and families. Prevention science designates 3 intervention categories: (1) universal prevention, targeting all individuals in the population, (2) selective interventions, targeting high-risk groups, and (3) indicated prevention interventions for youth with risk-taking behaviors. School-based and non-school-based interventions are reviewed, as well as the limitations of existing research, gaps in access and availability, and directions for future research and development.

Telemental health for children and adolescents.

Most children and adolescents across the USA fail to receive adequate mental health services, especially in rural or underserved communities. The supply of child and adolescent psychiatrists is insufficient for the number of children in need of services and is not anticipated to grow. This calls for novel approaches to mental health care. Telemental health (TMH) offers one approach to increase access. TMH programmes serving young people are developing rapidly and available studies demonstrate that these services are feasible, acceptable, sustainable and likely as effective as in-person services. TMH services are utilized in clinical settings to provide direct care and consultation to primary care providers (PCPs), as well as in non-traditional settings, such as schools, correctional facilities and the home. Delivery of services to young people through TMH requires several adjustments to practice with adults regarding the model of care, cultural values, participating adults, rapport-building, pharmacotherapy and psychotherapy. Additional infrastructure accommodations at the patient site include space and staffing to conduct developmentally appropriate evaluations and treatment planning with parents, other providers, and community services. For TMH to optimally impact young people's access to mental health care, collaborative models of care are needed to support PCPs as frontline mental health-care providers, thereby effectively expanding the child and adolescent mental health workforce.

Essential and synergistic roles of RP1 and RP1L1 in rod photoreceptor axoneme and retinitis pigmentosa.

Retinitis pigmentosa 1 (RP1) is a common inherited retinopathy with variable onset and severity. The RP1 gene encodes a photoreceptor-specific, microtubule-associated ciliary protein containing the doublecortin (DCX) domain. Here we show that another photoreceptor-specific Rp1-like protein (Rp1L1) in mice is also localized to the axoneme of outer segments (OSs) and connecting cilia in rod photoreceptors, overlapping with Rp1. Rp1L1-/- mice display scattered OS disorganization, reduced electroretinogram amplitudes, and progressive photoreceptor degeneration, less severe and slower than in Rp1-/- mice. In single rods of Rp1L1-/-, photosensitivity is reduced, similar to that of Rp1-/-. While individual heterozygotes are normal, double heterozygotes of Rp1 and Rp1L1 exhibit abnormal OS morphology and reduced single rod photosensitivity and dark currents. The electroretinogram amplitudes of double heterozygotes are more reduced than those of individual heterozygotes combined. In support, Rp1L1 interacts with Rp1 in transfected cells and in retina pull-down experiments. Interestingly, phototransduction kinetics are normal in single rods and whole retinas of individual or double Rp1 and Rp1L1 mutant mice. Together, Rp1 and Rp1L1 play essential and synergistic roles in affecting photosensitivity and OS morphogenesis of rod photoreceptors. Our findings suggest that mutations in RP1L1 could underlie retinopathy or modify RP1 disease expression in humans.

Buffer Standards for the Physiological pH of the Zwitterionic Compound, DIPSO from 5 to 55 degrees C.

The values of the second dissociation constant, pK(2), and related thermodynamic quantities of 3-[N,N-bis (2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid (DIPSO) have already been reported over the temperature range 5 to 55 degrees C including 37 degrees C. This paper reports the pH values of four NaCl-free buffer solutions and four buffer composition containing NaCl salt at I = 0.16 mol.kg(-1). Conventional pa(H) values are reported for all eight buffer solutions. The operational pH values have been calculated for four buffer solutions recommended as pH standards, at 25 and 37 degrees C after correcting the liquid junction potentials with the flowing junction cell.

Buffer Standards for the Biochemical pH of 3-(N-morpholino)-2-hydroxypropanesulfonic Acid from (278.15 to 328.15) K.

The values of the second dissociation constant pK(2) and related thermodynamic quantities of the ampholyte 3-(N-morpholino)-2-hydroxypropanesulfonic acid (MOPSO) have been previously determined at temperatures from (278.15 to 328.15) K. In this study, the pH values of two buffer solutions without NaCl and three buffer solutions with NaCl having ionic strengths (I = 0.16 mol·kg(-1)) similar to those in blood plasma, have been evaluated at 12 temperatures from (278.15 to 328.15) K using an extended form of the Debye-Hückel equation, since the Bates-Guggenheim convention is valid up to I = 0.1 mol·kg(-1). The liquid junction potentials (E(j)) between the buffer solutions of MOPSO and saturated KCl solution of the calomel electrode at (298.15 and 310.15) K have been estimated by measurement with a flowing junction cell. These values of E(j) have been used to ascertain the operational pH values at (298.15 and 310.15) K. Three buffer solutions of MOPSO are recommended as useful reference solutions for pH measurements in saline media of ionic strength I = 0.16 mol·kg(-1).