Impact of passive and active promotional strategies on patient acceptance of medication therapy management services

Objectives To assess the impact of passive and active promotional strategies on patient acceptance of medication therapy management (MTM) services, and to identify reasons for patient acceptance or refusal. Methods Four promotional approaches were developed to offer MTM services to eligible patients, including letters and bag stuffers (“passive” approaches), and face-to-face offers and telephone calls (“active” approaches). Thirty pharmacies in a grocery store chain were randomized to one of the four approaches. Patient acceptance rates were compared among the four groups, and between active and passive approaches using hierarchical logistic regression techniques. Depending on their decision to accept or decline the service, patients were invited to take part in one of two brief telephone surveys. Results No significant differences were identified among the four promotional methods or between active and passive methods in the analyses. Patients’ most frequent reasons for accepting MTM services were potential cost savings, review of how the medications were working, the expert opinion of the pharmacist, and education about medications. Patients’ most frequent reasons for declining MTM services were that the participant already felt comfortable with their medications and felt their pharmacist provides these services on a regular basis. Conclusion No significant difference was found among any of the four groups or between active or passive approaches. Further research is warranted to identify strategies for improving patient engagement in MTM services

PPARα and PPARγ activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective

Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumors displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent, dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma exposure levels sufficient for inhibition of PPARα/γ transcriptional activity did not result in significant anti-mesothelioma activity in mice. Lastly, we demonstrate that the in vitro anti-tumor effect of GW6471 is off-target. We conclude that dual PPARα/γ antagonism alone is not a viable treatment modality for mesothelioma

Supermarket Healthy Eating for Life (SHELf): protocol of a randomised controlled trial promoting healthy food and beverage consumption through price reduction and skill-building strategies

Background: In the context of rising food prices, there is a need for evidence on the most effective approaches for promoting healthy eating. Individually-targeted behavioural interventions for increasing food-related skills show promise, but are unlikely to be effective in the absence of structural supports. Fiscal policies have been advocated as a means of promoting healthy eating and reducing obesity and nutrition-related disease, but there is little empirical evidence of their effectiveness. This paper describes the Supermarket Healthy Eating for LiFe (SHELf) study, a randomised controlled trial to investigate effectiveness and cost-effectiveness of a tailored skill-building intervention and a price reduction intervention, separately and in combination, against a control condition for promoting purchase and consumption of healthy foods and beverages in women from high and low socioeconomic groups.Methods/design: SHELf comprises a randomised controlled trial design, with participants randomised to receive either (1) a skill-building intervention; (2) price reductions on fruits, vegetables and low-joule soft drink beverages and water; (3) a combination of skill-building and price reductions; or (4) a control condition. Five hundred women from high and low socioeconomic areas will be recruited through a store loyalty card program and local media. Randomisation will occur on receipt of informed consent and baseline questionnaire. An economic evaluation from a societal perspective using a cost-consequences approach will compare the costs and outcomes between intervention and control groups.Discussion: This study will build on a pivotal partnership with a major national supermarket chain and the Heart Foundation to investigate the effectiveness of intervention strategies aimed at increasing women&rsquo;s purchasing and consumption of fruits and vegetables and decreased purchasing and consumption of sugar-sweetened beverages. It will be among the first internationally to examine the effects of two promising approaches - skill-building and price reductions - on diet amongst women.<br /

Neighbourhood built environment associations with body size in adults:mediating effects of activity and sedentariness in a cross-sectional study of New Zealand adults

Background: The aim of this study was to determine the associations between body size and built environment walkability variables, as well as the mediating role of physical activity and sedentary behaviours with body size. Methods: Objective environment, body size (body mass index (BMI), waist circumference (WC)), and sedentary time and physical activity data were collected from a random selection of 2033 adults aged 20-65 years living in 48 neighbourhoods across four New Zealand cities. Multilevel regression models were calculated for each comparison between body size outcome and built environment exposure. Results and Discussion: Street connectivity and neighborhood destination accessibility were significant predictors of body size (1 SDchange predicted a 1.27 to 1.41 % reduction in BMI and a 1.76 to 2.29 % reduction in WC). Significantrelationships were also observed for streetscape (1 SD change predicted a 1.33 % reduction in BMI) anddwelling density (1 SD change predicted a 1.97 % reduction in BMI). Mediation analyses revealed asignificant mediating effect of physical activity on the relationships between body size and street connectivity and neighbourhood destination accessibility (explaining between 10.4 and 14.6 % of the total effect). No significant mediating effect of sedentary behaviour was found. Findings from this cross-sectional study of a random selection of New Zealand adults are consistent with international research. Findings are limited to individual environment features only; conclusions cannot be drawn about the cumulative and combined effect of individual features on outcomes. Conclusions: Built environment features were associated with body size in the expected directions. Objectively-assessed physical activity mediated observed built environment-body size relationships

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

PPARα and PPARγ activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective

Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumours displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma exposure levels sufficient for inhibition of PPARα/γ transcriptional activity did not result in significant anti-mesothelioma activity in mice. Lastly, we demonstrate that the in vitro antitumour effect of GW6471 is off-target. We conclude that dual PPARα/γ antagonism alone is not a viable treatment modality for mesothelioma