Yugo Ishihara

Background: Venlafaxine (VEN) is converted to O‐desmethylvenlafaxine (ODV) mainly through CYP2D6‐mediated O‐demethylation. However, age‐related clinical factors may also influence VEN exposure in routine practice. We examined whether age and CYP2D6 genotype show different associations with parent‐drug exposure and metabolic conversion. Methods: This retrospective therapeutic drug monitoring analysis included 78 Japanese psychiatric patients with available plasma VEN and ODV concentrations and CYP2D6 genotype data. Two prespecified outcomes were analyzed without body‐weight correction: VEN concentration divided by daily dose (VEN/dose) and the ODV/VEN ratio. CYP2D6*10 and *5 were coded as reduced‐ and no‐function alleles, respectively. Log‐transformed outcomes were analyzed using regression models including age and CYP2D6 reduced/no‐function allele count. Results: Nineteen patients (24.4%) were aged 65 years or older. Age was correlated with VEN/dose (Spearman rho = 0.295, p = 0.0086), and older patients had higher VEN/dose than younger patients (median, 0.522 vs. 0.192 [ng/mL]/[mg/day], p = 0.0127). In regression analysis, the incremental R ² for age was numerically larger than that for CYP2D6 allele count for VEN/dose (incremental R ² , 0.058 vs. 0.026). Conversely, the ODV/VEN ratio was strongly associated with CYP2D6 allele count (standardized beta = −0.391, p < 0.001; incremental R ² = 0.145) but not with age. Age‐by‐genotype interactions were not significant for either outcome. Conclusions: Age appeared to be more closely related to dose‐corrected parent VEN exposure, whereas CYP2D6 genotype predominantly determined the ODV/VEN metabolic ratio. The relative contribution of age should be interpreted descriptively because no formal comparison of effect sizes was performed. Separating exposure and metabolic‐ratio outcomes may clarify how geriatric and pharmacogenetic factors contribute to VEN disposition.

Background: High levels of physical activity are key to improving health outcomes, yet many people fail to take action. Using pedometers to target steps per day and providing financial incentives is a simple and scalable approach to promoting public health. However, conventional pedometers do not account for “intensity” and “duration,” making it challenging to efficiently increase people’s moderate-to-vigorous physical activity (MVPA), which is expected to improve health outcomes. Based on these rationales, we developed a smartphone app that sets step cadence as a goal (defined as a daily challenge of walking more than 1500 steps in 15 minutes twice a day, which is a heuristic threshold for moderate physical activity) and provides financial incentive when the challenge is met. Objective: This study aimed to evaluate the feasibility of our novel app and explore whether its use can increase users’ daily MVPA. Methods: A single-arm pre-post study evaluated the feasibility and efficacy of the app. A total of 15 participants used app 1 (an app without financial incentives) for the first period (4 weeks) and then switched to app 2 (an app with financial incentives) for the second period (4 weeks). The primary outcome was the difference between the first and second periods in the number of successful challenge attempts per week. Secondary outcomes were differences between the first and second periods in daily steps and distance walked. Exploratory outcomes included the difference between the first and second periods in daily “heart points” as measured by Google Fit, a publicly available app that measures users’ daily MVPA. Results: The number of successful challenge attempts per week increased significantly compared to the first period (5.6 times per week vs 0.7 times per week; P<.001). Although not statistically significant, there was a trend toward an increase in the mean steps per day and distance walked per day (6586 steps per day vs 5950 steps per day; P=.19; and 4.69 km per day vs 3.85 km per day; P=.09, respectively). An exploratory end point examining daily MVPA by “heart points” collected from Google Fit also showed a significant increase compared to the first period (22.7 points per day vs 12.8 points per day; P=.02). Conclusions: Our app using step cadence as a goal and providing financial incentives seemed feasible and could be an effective app to increase users’ daily MVPA. Based on the results of this study, we are motivated to conduct a confirmatory study with a broader and larger number of participants. Trial Registration: UMIN 000050518; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000057420

BACKGROUND High levels of physical activity are key to improving health outcomes, yet many people fail to take action. Using pedometers to target steps per day and providing financial incentives is a simple and scalable approach to promoting public health. However, conventional pedometers do not account for “intensity” and “duration,” making it challenging to efficiently increase people’s moderate-to-vigorous physical activity (MVPA), which is expected to improve health outcomes. Based on these rationales, we developed a smartphone app that sets step cadence as a goal (defined as a daily challenge of walking more than 1500 steps in 15 minutes twice a day, which is a heuristic threshold for moderate physical activity) and provides financial incentive when the challenge is met. OBJECTIVE This study aimed to evaluate the feasibility of our novel app and explore whether its use can increase users’ daily MVPA. METHODS A single-arm pre-post study evaluated the feasibility and efficacy of the app. A total of 15 participants used app 1 (an app without financial incentives) for the first period (4 weeks) and then switched to app 2 (an app with financial incentives) for the second period (4 weeks). The primary outcome was the difference between the first and second periods in the number of successful challenge attempts per week. Secondary outcomes were differences between the first and second periods in daily steps and distance walked. Exploratory outcomes included the difference between the first and second periods in daily “heart points” as measured by Google Fit, a publicly available app that measures users’ daily MVPA. RESULTS The number of successful challenge attempts per week increased significantly compared to the first period (5.6 times per week vs 0.7 times per week; P<.001). Although not statistically significant, there was a trend toward an increase in the mean steps per day and distance walked per day (6586 steps per day vs 5950 steps per day; P=.19; and 4.69 km per day vs 3.85 km per day; P=.09, respectively). An exploratory end point examining daily MVPA by “heart points” collected from Google Fit also showed a significant increase compared to the first period (22.7 points per day vs 12.8 points per day; P=.02). CONCLUSIONS Our app using step cadence as a goal and providing financial incentives seemed feasible and could be an effective app to increase users’ daily MVPA. Based on the results of this study, we are motivated to conduct a confirmatory study with a broader and larger number of participants. CLINICALTRIAL UMIN 000050518; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000057420