Validation of brief screening measures for depression and anxiety in young people with substance use disorders.

BACKGROUND: It is critical to promptly identify and monitor mood and anxiety symptoms in young people with SUD. The primary aim of this study was to conduct a psychometric validation of the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) for depression and anxiety screening in young people seeking outpatient treatment for SUD. Our secondary aim was to compare the performance of the PHQ-9 and GAD-7 to their briefer two-item versions (PHQ-2 and GAD-2) in terms of detecting probable mood and anxiety disorders. METHOD: Data were extracted from the electronic health records of patients (ages 14 to 26) who received a diagnostic evaluation following clinical implementation of the PHQ-9 and GAD-7 at a hospital-based outpatient SUD treatment program (N=121, average age 19.1 ± 3.1 years). RESULTS: The PHQ-9 and GAD-7 showed excellent internal consistency. A PHQ-9 cut score of 7 or 8 (PHQ-2 cut score: 2) and GAD-7 cut score of 6 (GAD-2 cut score: 2) had the best balance of sensitivity, specificity, and positive and negative predictive power in these data. These measures also showed good convergent and acceptable discriminant validity. LIMITATIONS: The sample was predominantly White and non-Hispanic, and a validated (semi-)structured diagnostic interview was not used to establish mood and anxiety disorder diagnoses. CONCLUSIONS: Results suggest the PHQ-9 and GAD-7 are reliable and potentially clinically useful screening tools for depression and anxiety in young people with SUD, and that the two-item versions may have similar clinical utility as the full measures.

Medical Writing Competency Model - Section 1: Functions, Tasks, and Activities.

This article provides Section 1 of the 2017 Edition 2 Medical Writing Competency Model that describes the core work functions and associated tasks and activities related to professional medical writing within the life sciences industry. The functions in the Model are scientific communication strategy; document preparation, development, and finalization; document project management; document template, standard, format, and style development and maintenance; outsourcing, alliance partner, and client management; knowledge, skill, ability, and behavior development and sharing; and process improvement. The full Model also includes Section 2, which covers the knowledge, skills, abilities, and behaviors needed for medical writers to be effective in their roles; Section 2 is presented in a companion article. Regulatory, publication, and other scientific writing as well as management of writing activities are covered. The Model was developed to aid medical writers and managers within the life sciences industry regarding medical writing hiring, training, expectation and goal setting, performance evaluation, career development, retention, and role value sharing to cross-functional partners.

Medical Writing Competency Model - Section 2: Knowledge, Skills, Abilities, and Behaviors.

This article provides Section 2 of the 2017 Edition 2 Medical Writing Competency Model that describes the knowledge, skills, abilities, and behaviors that professional medical writers need in order to perform effectively within the life sciences industry. What a medical writer should know, what they should be able to do, and how they should use this knowledge and these skills to facilitate their primary work function is a focus. Regulatory, publication, and other scientific writing as well as management of writing activities are covered. The full Model also includes Section 1, which covers the core work functions and associated tasks and activities related to professional medical writing within the life sciences industry; Section 1 is included in a companion article. The Model was developed to aid medical writers and managers within the life sciences industry regarding medical writing hiring, training, expectation and goal setting, performance evaluation, career development, retention, and role value sharing to cross-functional partners.

Application of stable isotope methodology in the evaluation of the pharmacokinetics of (S,S)-3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine hydrochloride in rats.

The primary objective of this study was to demonstrate the use of stable isotope (SI)-labeled compound as an approach for pharmacokinetic analysis such as fraction absorbed, hepatic extraction ratio, and fraction metabolized from the parent drug to a metabolite. (S,S)-3-[3-(Methylsulfonyl)phenyl]-1-propylpiperidine hydrochloride (PNU96391) was selected as the model compound because of its simple biotransformation pathway, i.e., the predominant metabolic pathway to the N-despropyl metabolite (M1), which makes it a suitable candidate. The second objective was to fully characterize the pharmacokinetics of PNU96391 in rats using the SI coadministration approach with quantitative analysis by liquid chromatography-tandem mass spectrometry. Overall the present study showed that 1) absorption of PNU96391 from the gastrointestinal tract was near complete (>90% of the dose), 2) PNU96391 was predominantly metabolized to M1 (approximately 70% of the dose), and 3) M1 was exclusively eliminated into urine with negligible biotransformation (ratio of renal clearance to plasma clearance approximately 0.9). Therefore, the present study demonstrated the utility of the SI methodology for characterizing the pharmacokinetics of a compound within the drug discovery and development process. Furthermore, the compartmental pharmacokinetic modeling provided insights into the disposition and biotransformation rates of PNU96391 and M1, suggesting that the modeling could add further advantages to the SI coadministration approach. Despite the greater availability of SI-labeled compounds, absorption, distribution, metabolism, and excretion (ADME) scientists have yet to take full advantage of the potential use of these analogs for mechanistic ADME studies. These SI-labeled compounds can be used more widely to gain a better understanding of ADME properties in drug discovery and development.

Comparison of prediction methods for in vivo clearance of (S,S)-3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine hydrochloride, a dopamine D2 receptor antagonist, in humans.

The purpose of this study is to investigate reliable prediction methods for in vivo pharmacokinetics and the likelihood of drug interactions with several cytochrome P450 inhibitors in humans for (S,S)-3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine (PNU-96391). By allometric scaling of in vivo animal data, clearance of PNU-96391 in humans was over-predicted by 4-fold, half-life was under-predicted by 3-fold, and volume of distribution was accurately predicted. High correlation coefficients (>0.99) were observed for these parameters. Neither the in vitro-in vivo correlation approach nor the modified allometric scaling with maximum life span potential or brain weight accurately provided the predicted clearance value. Using an alternative method, based on normalization of in vitro human data with the ratio of in vivo to in vitro animal data, the in vivo clearance in humans was predicted to be 0.39 l/h/kg. This value correlated well with the in vivo value (0.43 l/h/kg). Regarding the interactions of PNU-96391 with cytochrome P450 inhibitors, only quinidine, haloperidol, and ketoconazole showed significant inhibition on the metabolic clearance of PNU-96391 in human hepatocytes. By comparing in vitro K(i) values with in vivo maximum unbound concentrations of the inhibitor, the increases in systemic exposure of PNU-96391 by coadministration of the inhibitors were estimated to be less than 1.5-fold. A preliminary comparison of pharmacokinetics of PNU-96391 between CYP2D6 extensive and poor metabolizers in the clinical study showed only a slight increase in systemic exposure in poor metabolizers (approximately 1.4-fold as area under the concentration-time curve). Therefore, clinically significant drug-drug interactions of PNU-96391 would be unlikely to occur with coadministration of CYP2D6 inhibitors.