Pharmacokinetics and Pharmacodynamics of Immediate-Release Versus Extended-Release Guanfacine in Adult Daily Smokers.

BACKGROUND: Guanfacine is Food and Drug Administration approved for hypertension and attention-deficit hyperactivity disorder and has been used off-label for migraine prophylaxis, heroin withdrawal, and more recently smoking cessation. Previous studies have shown positive effects of 3 mg/d of immediate-release (IR) guanfacine on smoking outcomes, but the dose equivalency of the IR and extended-release (ER) formulations is unknown. PROCEDURES: A within-subject design was used to compare the pharmacokinetics and pharmacodynamics of 3 mg/d of IR, 4 mg/d of ER, and 6 mg/d of ER guanfacine in adult daily smokers (n = 5). Plasma medication levels, vital signs, cigarettes per day, tobacco craving, and adverse events were assessed. Medication was titrated to stable dosing after each laboratory day (3 mg/d IR, then 4 mg/d ER, then 6 mg/d ER). RESULTS: Plasma medication levels did not differ between the 3 mg/d of IR and 4 mg/d of ER doses after 24 hours from last dose and were highest at the 6 mg/d of ER dose (3 mg/d IR: M = 3.40 ng/mL, SE = 0.34 vs 4 mg/d ER: M = 3.46 ng/mL, SE = 0.67 vs 6 mg/d ER: M = 5.92 ng/mL, SE = 1.02). All doses of guanfacine decreased heart rate and blood pressure from baseline. Absolute values of cigarettes per day (6 mg/d ER) and tobacco craving (4 and 6 mg/d ER) were lowest with the ER formulations. Treatment-emergent adverse events were subject rated as minimal to mild, except dry mouth. CONCLUSIONS: We demonstrated similar pharmacokinetic profiles between 3 mg/d of IR guanfacine and 4 mg/d of ER guanfacine, as hypothesized. All doses of guanfacine were well tolerated.

Intensive, Real-Time Data Collection of Psychological and Physiological Stress During a 96-Hour Field Training Exercise at a Senior Military College: Feasibility and Acceptability Cohort Study.

BACKGROUND: Poor physical fitness, stress, and fatigue are factors impacting military readiness, national security, and economic burden for the United States Department of Defense. Improved accuracy of wearable biosensors and remote field biologic sample collection strategies could make critical contributions to understanding how physical readiness and occupational stressors result in on-the-job and environment-related injury, sleep impairments, diagnosis of mental health disorders, and reductions in performance in war-fighters. OBJECTIVE: This study aimed to evaluate the feasibility and acceptability of intensive biomarker and biometric data collection to understand physiological and psychological stress in Army Reserved Officer Training Corps cadets before, during, and after a 96-hour field training exercise (FTX). METHODS: A prospective pilot study evaluated the feasibility and acceptability of multimodal field data collection using passive drool saliva sampling, sweat sensors, accelerometry, actigraphy, and photoplethysmography. In addition, physical fitness (Army Combat Fitness Test), self-reported injury, and psychological resilience (Brief Resilience Scale) were measured. RESULTS: A total of 22 cadets were included. Two were lost to follow-up due to injury during FTX, for a retention rate of 91%. Assessments of performance and psychological resilience were completed for all remaining participants, resulting in 100% testing adherence. All participants provided saliva samples before the FTX, with 98% adherence at the second time point and 91% at the third. For sweat, data collection was not possible. Average daily wear time for photoplethysmography devices was good to excellent, meeting a 70% threshold with data collected for ≥80% of person-days at all time points. Of the participants who completed the FTX and 12 completed a post-FTX acceptability survey for a response rate of 60%. Overall, participant acceptance was high (≥80%) for all metrics and devices. CONCLUSIONS: This study demonstrates that wearable biosensors and remote field biologic sample collection strategies during a military FTX have the potential to be used in higher stakes tactical environments in the future for some, but not all, of the strategies. Overall, real-time biometric and biomarker sampling is feasible and acceptable during field-based training and provides insights and strategies for future interventions on military cadet and active-duty readiness, environmental stress, and recovery.

Establishing a Global Standard for Wearable Devices in Sport and Exercise Medicine: Perspectives from Academic and Industry Stakeholders.

Millions of consumer sport and fitness wearables (CSFWs) are used worldwide, and millions of datapoints are generated by each device. Moreover, these numbers are rapidly growing, and they contain a heterogeneity of devices, data types, and contexts for data collection. Companies and consumers would benefit from guiding standards on device quality and data formats. To address this growing need, we convened a virtual panel of industry and academic stakeholders, and this manuscript summarizes the outcomes of the discussion. Our objectives were to identify (1) key facilitators of and barriers to participation by CSFW manufacturers in guiding standards and (2) stakeholder priorities. The venues were the Yale Center for Biomedical Data Science Digital Health Monthly Seminar Series (62 participants) and the New England Chapter of the American College of Sports Medicine Annual Meeting (59 participants). In the discussion, stakeholders outlined both facilitators of (e.g., commercial return on investment in device quality, lucrative research partnerships, and transparent and multilevel evaluation of device quality) and barriers (e.g., competitive advantage conflict, lack of flexibility in previously developed devices) to participation in guiding standards. There was general agreement to adopt Keadle et al.'s standard pathway for testing devices (i.e., benchtop, laboratory, field-based, implementation) without consensus on the prioritization of these steps. Overall, there was enthusiasm not to add prescriptive or regulatory steps, but instead create a networking hub that connects companies to consumers and researchers for flexible guidance navigating the heterogeneity, multi-tiered development, dynamicity, and nebulousness of the CSFW field.