Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

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

Strategies for discussing long-term prognosis when deciding on cancer screening for adults over age 75

BackgroundConsideration of older adults’ 10-year prognosis is necessary for high-quality cancer screening decisions. However, few primary care providers (PCPs) discuss long-term (10-year) prognosis with older adults.MethodsTo learn PCPs’ and older adults’ perspectives on and to develop strategies for discussing long-term prognosis in the context of cancer screening decisions, we conducted qualitative individual interviews with adults 76–89 and focus groups or individual interviews with PCPs. We recruited participants from 4 community and 2 academic Boston-area practices and completed a thematic analysis of participant responses to open-ended questions on discussing long-term prognosis.ResultsForty-five PCPs (21 community-based) participated in 7 focus groups or 7 individual interviews. Thirty patients participated; 19 (63%) were female, 13 (43%) were non-Hispanic Black, and 13 (43%) were non-Hispanic white. Patients and PCPs had varying views on the utility of discussing long-term prognosis. “For some patients and for some families having this information is really helpful,” (PCP participant). Some participants felt that prognostic information could be helpful for future planning, whereas others thought the information could be anxiety-provoking or of “no value” because death is unpredictable; still others were unsure about the value of these discussions. Patients often described thinking about their own prognosis. Yet, PCPs described feeling uncomfortable with these conversations. Patients recommended that discussion of long-term prognosis be anchored to clinical decisions, that information be provided on how this information may be useful, and that patient interest in prognosis be assessed before prognostic information is offered. PCPs recommended that scripts be brief. These recommendations were used to develop example scripts to guide these conversations.ConclusionsWe developed scripts and strategies for PCPs to introduce the topic of long-term prognosis with older adults and to provide numerical prognostic information to those interested. Future studies will need to test the effect of these strategies in practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/173015/1/jgs17723-sup-0001-supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/173015/2/jgs17723.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/173015/3/jgs17723_am.pd

Scripts and Strategies for Discussing Stopping Cancer Screening with Adults &gt; 75 Years: a Qualitative Study

BackgroundDespite guidelines recommending not to continue cancer screening for adults &gt; 75&nbsp;years old, especially those with short life expectancy, primary care providers (PCPs) feel ill-prepared to discuss stopping screening with older adults.ObjectiveTo develop scripts and strategies for PCPs to use to discuss stopping cancer screening with adults &gt; 75.DesignQualitative study using semi-structured interview guides to conduct individual interviews with adults &gt; 75&nbsp;years old and focus groups and/or individual interviews with PCPs.ParticipantsForty-five PCPs and 30 patients &gt; 75&nbsp;years old participated from six community or academic Boston-area primary care practices.ApproachParticipants were asked their thoughts on discussions around stopping cancer screening and to provide feedback on scripts that were iteratively revised for PCPs to use when discussing stopping mammography and colorectal cancer (CRC) screening.ResultsTwenty-one (47%) of the 45 PCPs were community based. Nineteen (63%) of the 30 patients were female, and 13 (43%) were non-Hispanic white. PCPs reported using different approaches to discuss stopping cancer screening depending on the clinical scenario. PCPs noted it was easier to discuss stopping screening when the harms of screening clearly outweighed the benefits for a patient. In these cases, PCPs felt more comfortable being more directive. When the balance between the benefits and harms of screening was less clear, PCPs endorsed shared decision-making but found this approach more challenging because it was difficult to explain why to stop screening. While patients were generally enthusiastic about screening, they also reported not wanting to undergo tests of little value and said they would stop screening if their PCP recommended it. By the end of participant interviews, no further edits were recommended to the scripts.ConclusionsTo increase PCP comfort and capability to discuss stopping cancer screening with older adults, we developed scripts and strategies that PCPs may use for discussing stopping cancer screening

Nonmuscle myosin light chain kinase activity modulates radiation-induced lung injury.

Radiotherapy as a primary treatment for thoracic malignancies induces deleterious effects, such as acute or subacute radiation-induced lung injury (RILI). Although the molecular etiology of RILI is controversial and likely multifactorial, a potentially important cellular target is the lung endothelial cytoskeleton that regulates paracellular gap formation and the influx of macromolecules and fluid to the alveolar space. Here we investigate the central role of a key endothelial cytoskeletal regulatory protein, the nonmuscle isoform of myosin light chain kinase (nmMLCK), in an established murine RILI model. Our results indicate that thoracic irradiation significantly augmented nmMLCK protein expression and enzymatic activity in murine lungs. Furthermore, genetically engineered mice harboring a deletion of the nmMLCK gene (nmMLCK(-/-) mice) exhibited protection from RILI, as assessed by attenuated vascular leakage and leukocyte infiltration. In addition, irradiated wild-type mice treated with two distinct MLCK enzymatic inhibitors, ML-7 and PIK (peptide inhibitor of kinase), also demonstrated attenuated RILI. Taken together, these data suggests a key role for nmMLCK in vascular barrier regulation in RILI and warrants further examination of RILI strategies that target nmMLCK.Electronically published April 19, 2016. 12 month embargo.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]