Using Videogame Apps to Assess Gains in Adolescents' Substance Use Knowledge: New Opportunities for Evaluating Intervention Exposure and Content Mastery.

BACKGROUND: Videogame interventions are becoming increasingly popular as a means to engage people in behavioral interventions; however, strategies for examining data from such interventions have not been developed. OBJECTIVE: The objective of this study was to describe how a technology-based intervention can yield meaningful, objective evidence of intervention exposure within a behavioral intervention. This study demonstrates the analysis of automatic log files, created by software from a videogame intervention, that catalog game play and, as proof of concept, the association of these data with changes in substance use knowledge as documented with standardized assessments. METHODS: We analyzed 3- and 6-month follow-up data from 166 participants enrolled in a randomized controlled trial evaluating a videogame intervention, PlayForward: Elm City Stories (PlayForward). PlayForward is a videogame developed as a risk reduction and prevention program targeting HIV risk behaviors (substance use and sex) in young minority adolescents. Log files were analyzed to extract the total amount of time spent playing the videogame intervention and the total number of game levels completed and beaten by each player. RESULTS: Completing and beating more of the game levels, and not total game play time, was related to higher substance use knowledge scores at the 3- (P=.001) and 6-month (P=.001) follow-ups. CONCLUSIONS: Our findings highlight the potential contributions a videogame intervention can make to the study of health behavior change. Specifically, the use of objective data collected during game play can address challenges in traditional human-delivered behavioral interventions. TRIAL REGISTRATION: Clinicaltrials.gov NCT01666496; https://clinicaltrials.gov/ct2/show/NCT01666496 (Archived by WebCite at http://www.webcitation.org/6cV9fxsOg).

Association of physical activity on blood glucose in individuals with type 2 diabetes.

Regular physical activity (PA) has been shown to improve glycemic control in persons with type 2 diabetes. This study aimed to investigate the impact of PA on blood glucose after controlling for medication use, demographics, and week of activation using a real-world population of individuals with type 2 diabetes. A longitudinal, retrospective study was performed evaluating weekly PA of Livongo members (N = 9,509), which analyzed fasting blood glucose (FBG), step counts, and daily active minutes. Linear mixed-effect modeling technique was used to investigate within member and between member effects of input variables on average weekly FBG. Of members enrolled, 6,336 (32%) had self-reported body mass index, qualified week with diabetes medications, and FBG measures. Members' baseline average age was 49.4 (SD 10.1) years old, 43% female, and 45,496 member weeks with an average of 7.2 qualified weeks (PA observable in ≥4 days) per member. Average weekly FBG was 140.5 mg/dL (SD 39.8), and average daily step counts were 4,833 (SD 3,266). Moving from sedentary (<5,000 steps per day) to active (≥5,000 steps per day) resulted in mean weekly FBG reduction of 13 mg/dL (95% CI: -22.6 to -3.14). One additional day of ≥8,000 steps reduced mean weekly FBG by 0.47 mg/dL (95% CI: -0.77 to -0.16). Members who completed 30 min of moderate to vigorous PA above the population average reduced mean weekly FBG by 7.7 mg/dL (95% CI: -13.4 to -2.0). PA is associated with a mean weekly FBG reduction of 13 mg/dL when changing from a sedentary to active lifestyle while participating in a remote diabetes monitoring program.

Treg depletion inhibits efficacy of cancer immunotherapy: implications for clinical trials.

BACKGROUND: Regulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients. FINDINGS: Using a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs present in tumors, draining lymph nodes and spleen and improved long-term survival (50% of mice survived >150 days). No improvement in survival was observed when Tregs were depleted 24 days after tumor implantation, suggesting that tumor burden is an important factor for determining efficacy of Treg depletion in clinical trials. In a T cell dependent model of brain tumor regression elicited by intratumoral delivery of adenoviral vectors (Ad) expressing Fms-like Tyrosine Kinase 3 ligand (Flt3L) and Herpes Simplex Type 1-Thymidine Kinase (TK) with ganciclovir (GCV), we demonstrate that administration of PC61 24 days after tumor implantation (7 days after treatment) inhibited T cell dependent tumor regression and long term survival. Further, depletion with PC61 completely inhibited clonal expansion of tumor antigen-specific T lymphocytes in response to the treatment. CONCLUSIONS: Our data demonstrate for the first time, that although Treg depletion inhibits the progression/eliminates GBM tumors, its efficacy is dependent on tumor burden. We conclude that this approach will be useful in a setting of minimal residual disease. Further, we also demonstrate that Treg depletion, using PC61 in combination with immunotherapy, inhibits clonal expansion of tumor antigen-specific T cells, suggesting that new, more specific targets to block Tregs will be necessary when used in combination with therapies that activate anti-tumor immunity.