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

Challenges in public health and epidemiology research in humanitarian settings: experiences from the field

Background: Humanitarian settings often present unique scientific challenges and conditions that distinguish them from standard research settings. While a number of these challenges are faced in both standard settings and humanitarian settings, factors unique to humanitarian settings such as inaccessibility and time sensitivities further exacerbate the effects of these challenges. This analysis focuses on experiences in post-disaster contexts such as Indonesia and India following the 2004 Indian Ocean Tsunami, the Philippines following Typhoon Haiyan in 2013, and Nepal following the 2015 earthquake. Discussion: Particular issues that we faced in undertaking research in post-disaster settings include challenges with uncharted ethical and cultural considerations, non-standardised administrative methods for record keeping, data sharing and dissemination. While these issues are not unique to post-disaster humanitarian settings, the timesensitive nature of our work exacerbated the effects of these concerns. Relying on local partners and making quick decisions to tackle issues is imperative for navigating both foreseen and unforeseen challenges. While pre-emptive action to address these concerns is the most efficient means to expedite research protocols, adaptability and contingency planning are key components of practical research implementation in dynamic situations. Conclusions: Research is not always a priority in humanitarian settings, so innovative methods are necessary to conduct meaningful and situationally appropriate research in these venues. By understanding available resources, local culture, and political considerations and working efficiently and decisively, we can begin to jump hurdles associated with epidemiologic research in humanitarian settings

Disease burden among refugees in camps on mainland Greece, 2016–2017: a retrospective cross-sectional study

Abstract Background Despite the importance of baseline health data for evidence-informed decision-making, these data are rarely available for displaced populations. At the height of the European refugee crisis, most of those seeking asylum in Europe were from regions with high prevalences of communicable and non-communicable diseases. To create an epidemiologic profile for refugees in camps on mainland Greece, this study assessed the prevalence of 11 communicable and non-communicable diseases among refugees utilizing Médecins du Monde (MdM) in-camp clinics. Methods The proportional morbidity of selected diseases among individuals utilizing MdM services were determined from data collected at refugee camp clinics on mainland Greece from April 2016 - July 2017. Overall and age-specific proportional morbidities were reported. Differences in disease burden among refugees from the largest sending countries - Afghanistan and Syria - were compared using proportional morbidity ratios and 95% confidence intervals. Patterns in results were compared with disease burden estimates in sending countries and with findings from comparable settings. Results Respiratory tract infections (RTIs) were the most prevalent outcome. Among RTIs, upper RTIs were most common, with a proportional morbidity of nearly 40%; throughout the study period, over 46% of children under 18 years had at least one upper RTI consultation. Musculoskeletal conditions (3.64%), were the most prevalent non-communicable outcome, followed by hypertension (2.21%) and asthma (1.28%). Afghans were 31.68% more likely than Syrians to have a consultation for at least one condition (PR: 1.32; 95% CI: 1.25, 1.39). The proportional morbidity of RTIs was comparable to sending countries, but there was a comparatively lower burden of other conditions among refugees than literature estimates from sending countries. Conclusion Refugees utilizing MdM clinics in camps had higher burdens of communicable diseases - predominantly RTIs - relative to non-communicable diseases. Non-communicable disease burdens were comparatively lower than reported prevalences from in-country populations. These findings can be attributed to a range of considerations including differences in demographic profiles between sending countries and refugee populations and missed opportunities for utilizing clinical care. Further investment is needed to capture the health profiles of displaced populations to support evidence-informed decision-making processes in humanitarian emergency responses

Predictors of exceeding emergency under-five mortality thresholds using small-scale survey data from humanitarian settings (1999 – 2020): considerations for measles vaccination, malnutrition, and displacement status

Background: Quantifying the effect of measles containing vaccine (MCV) coverage and the prevalence of global acute malnutrition (GAM) on mortality levels in populations of displaced and crisis-affected resident children is important for intervention programming in humanitarian emergencies. Methods: A total of 1597 surveys containing data on under-five death rate, population status (internally displaced, refugee, or crisis-affected resident), measles containing vaccine coverage, and global acute malnutrition were extracted from the Complex Emergency Database (CE-DAT). Under-five mortality rates were dichotomized to those exceeding critical levels or otherwise. A Bayesian multivariable mixed-effect logistic regression model was used to assess the association between an under-five death rate (U5DR) exceeding this threshold and population status (i.e., internally displaced, refugees or residents), GAM prevalence (proxy for food security), and MCV coverage. Results: The prevalence of GAM, MCV and U5DR were higher in internally displaced children (IDC) with values of 14.6%, 69.9% and 2.07 deaths per 10 000 per day, respectively. Refugee populations had lower average under-five mortality rate (0.89 deaths per 10 000 per day), GAM of 12.0% and the highest measles containing vaccine coverage (80.0%). In crisis-affected residents the prevalence of GAM, MCV and average U5DR are 11.1%, 65.5% and 1.20 deaths per 10 000 per day respectively. In mixed-effect logistic model taking 2 deaths per 10 000 children less than five years old per as emergency threshold (Model III); MCV (AOR = 0.66, 95% Highest Density Interval (HDI): 0.57, 0.78), GAM (AOR = 1.79, 95% HDI: 1.52, 2.12) were associated with a reduction of the odds of U5DR exceeding critical level accounting for country-specific levels of variability. The odds of U5DR exceeding critical level (2/10000/day) in crisis-affected resident children and refugees were 0.36 (95% HDI: 0.22, 0.58) and 0.25(95% HDI: 0.11, 0.55) less than amongst IDP children adjusting for GAM and MCV. In considering country specific yearly median U5DR (model IV) the odds of U5DR exceeding twice the median U5DR were associated with MCV (AOR = 0.72, 95% HDI: 0.64, 0.82), GAM (AOR = 1.53, 95%HDI: 1.34, 1.76). The odds of U5DR exceeding critical level in crisis-affected resident children was 0.30(95% HDI: 0.20, 0.45) less than IDP children, after adjusting for MCV and GAM. We found no difference between the odds of U5DR exceeding twice the country level median U5DR in the refugee population compared to the IDPs. Conclusions: In this study vaccination coverage and global acute malnutrition (proxy for food security) were associated with U5DR exceeding critical level. The emergency threshold for IDPs and affected residents is significantly different and consistent across the different outcomes, whereas the result is inconsistent for IDPs and refugees. Continued improvement in measles vaccination coverage and reduction of malnutrition in humanitarian emergencies have the potential to minimize the deterioration of mortality level amongst children in emergency settings. To generate a robust understanding of the critical level of child mortality in displaced and affected resident populations, studies accounting for the impact of the duration of displacement, contextual factors in humanitarian settings, and the level of humanitarian assistance provided are needed

Civil war and death in Yemen: Analysis of SMART survey and ACLED data, 2012–2019

Conflict in Yemen has displaced millions and destroyed health infrastructure, resulting in the world’s largest humanitarian disaster. The objective of this paper is to examine mortality in Yemen to determine whether it has increased significantly since the conflict began in 2015 compared to the preceding period. We analysed 91 household surveys using the Standardized Monitoring and Assessment of Relief and Transitions methodology, covering 2,864 clusters undertaken from 2012–2019, and deaths from Armed Conflict Location & Event Data Project database covering the conflict period 2015–2019. We used a Poisson-Gamma model to estimate pre-conflict (μp, baseline value) and conflict period (μc) mean death rates using household survey data from 2012–2019. To analyse changes in the distribution of deaths and estimate nationwide excess deaths, we applied pre- and post-conflict death rates to total population numbers. Further, we tested for association between excess death and security levels by governorate. The national estimated crude death rate/10,000 in the conflict period was 0.20 (95% CI: 0.17, 0.24), which is meaningfully higher than the estimated baseline rate of 0.19 (95% CI: 0.17, 0.22). Applying the conflict period rate to the Yemeni population, we estimated 168,212 excess deaths that occurred between 2015 and 2019. There was an 17.8% increase in overall deaths above the baseline during the conflict period. A large share (67.2%) of the excess deaths were due to combat-related violence. At the governorate level, posterior crude death rate varied across the country, ranging from 0.03 to 0.63 per 10,000 per day. Hajjah, Ibb, and Al Jawf governorates presented the highest total excess deaths. Insecurity level was not statistically associated with excess deaths. The health situation in Yemen was poor before the crisis in 2015. During the conflict, intentional violence from air and ground strikes were responsible for more deaths than indirect or non-violent causes. The provision of humanitarian aid by foreign agencies may have helped contain increases in indirect deaths from the conflict

The Centre of Excellence in Cancer Prevention Archive of Website Blog Posts (October 2013 to October 2018)

The Centre of Excellence in Cancer Prevention Blog was a web-based resource that was published online for five years (October 2013 through October 2018). The blog provided a regular source of accessible, evidence-based and current information on cancer prevention topics written by experts in the field. It was developed to be a useful and interesting resource for researchers, students, community organizations, policymakers, and members of the public interested in learning more about cancer prevention. Authors of blog posts include faculty from the University of British Columbia, Vancouver and Okanagan campuses, and the University of Victoria, students and staff at the Centre of Excellence in Cancer Prevention, BC Cancer, and community organizations (Canadian Cancer Society British Columbia Yukon, Canadian Cancer Society National, the BC Healthy Living Alliance, and the Canadian Men’s Health Foundation). Collectively, the blog topics comprise a tour de force of the field of cancer prevention, with special focus on activities carried out by the Centre of Excellence in Cancer Prevention and in Canada more widely during this time period. Blogs include attention to a wide array of cancer risk factors (energy balance, shiftwork, tobacco, sun exposure, nutrition, radioactivity, infections, alcohol, obesity, physical activity, and environmental exposures including climate change). A number of defined population groups with special concerns are highlighted, including Aboriginal Canadians, South Asian immigrants, gay men, men in general, Filipinos, and international variation. Issues that affect the population as a whole are also addressed, including economics, taxation, complementary and alternative medicine, and socioeconomic status. Specific intervention programs at the Centre of Excellence in Cancer Prevention are highlighted (e.g., the Breast Cancer Prevention and Risk Assessment Clinic, Cooking Class for Prostate Cancer Patients and Partners, Cancer Prevention 101, and the shiftworkers project), as well as other programs in BC and Canada (e.g., Food Explorers, It’s My Life). Please note that this is an archive and hyperlinks are no longer active.Health and Social Development, Faculty of (Okanagan)Medicine, Faculty ofNon UBCExperimental Medicine, Division ofNursing, School of (Okanagan)Physical Therapy, Department ofPopulation and Public Health (SPPH), School ofUnreviewedFacultyResearcherGraduateOthe

Metadata record for: HIT-COVID, a global database tracking public health interventions to COVID-19

This dataset contains key characteristics about the data described in the Data Descriptor HIT-COVID, a global database tracking public health interventions to COVID-19. Contents: 1. human readable metadata summary table in CSV format 2. machine readable metadata file in JSON forma