Optimizing the use of continuous glucose monitoring in young children with type 1 diabetes with an adaptive study design and multiple randomizations

Parents of young children with type 1 diabetes (T1D) experience unique, developmental challenges in managing their child's T1D, resulting in psychosocial distress. Only a small portion of young children reach glucose goals and adherence to diabetes devices that help improve T1D management have historically been low in this population. The purpose of this study is to test four interventions that couple developmentally tailored behavioral supports with education to optimize use of diabetes devices, improve glucose control, and reduce psychosocial distress for parents of young children with T1D. The study team designed four behavioral interventions, two aimed at improving glucose control and two aimed at optimizing use of diabetes devices. The goal of this paper is to describe the behavioral interventions developed for this study, including the results of a pilot test, and describe the methods and analysis plan to test this intervention strategy with ninety participants in a large-scale, randomized trial using a sequential multiple assignment randomization trial (SMART) design. A SMART design will permit a clinically relevant evaluation of the intervention strategy, as it allows multiple randomizations based on individualized assessments throughout the study instead of a fixed intervention dose seen in most traditional randomized controlled trials

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Forouzanfar MH, Afshin A, Alexander LT, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. LANCET. 2016;388(10053):1659-1724.Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57.8% (95% CI 56.6-58.8) of global deaths and 41.2% (39.8-42.8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211.8 million [192.7 million to 231.1 million] global DALYs), smoking (148.6 million [134.2 million to 163.1 million]), high fasting plasma glucose (143.1 million [125.1 million to 163.5 million]), high BMI (120.1 million [83.8 million to 158.4 million]), childhood undernutrition (113.3 million [103.9 million to 123.4 million]), ambient particulate matter (103.1 million [90.8 million to 115.1 million]), high total cholesterol (88.7 million [74.6 million to 105.7 million]), household air pollution (85.6 million [66.7 million to 106.1 million]), alcohol use (85.0 million [77.2 million to 93.0 million]), and diets high in sodium (83.0 million [49.3 million to 127.5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Copyright (C) The Author(s). Published by Elsevier Ltd

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

Simple treatments for complex problems : a flexible cognitive behavior analysis system approach to psychotherapy/ Kimberly A. Driscoll (et.al)

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Psychologists and the Transition From Pediatrics to Adult Health Care.

PURPOSE: Guidelines for optimal transition call for multidisciplinary teams, including psychologists, to address youth and young adults’ multifactorial needs. This study aimed to characterize psychologists’ roles in and barriers to involvement in transition from pediatric to adult healthcare. METHODS: Psychologists were invited via professional listservs to complete an online survey about practice settings, roles in transition programming, barriers to involvement, and funding sources. Participants also responded to open-ended questions about their experiences in transition programs. RESULTS: One hundred participants responded to the survey. Involvement in transition was reported at multiple levels from individual patient care to institutional transition programming, and 65% reported more than one level of involvement. Direct clinical care (88%), transition-related research (50%) and/or leadership (44%) involvement were reported, with 59% reporting more than one role. Respondents often described advocating for their involvement on transition teams. Various sources of funding were reported, yet 23% reported no funding for their work. Barriers to work in transition were common and included healthcare systems issues such as poor coordination among providers or lack of a clear transition plan within the clinic/institution. CONCLUSIONS: Psychologists assume numerous roles in the transition of adolescents from pediatric to adult healthcare. With training in healthcare transition-related issues, psychologists are ideally positioned to partner with other health professionals to develop and implement transition programs in multi-disciplinary settings, provided healthcare system barriers can be overcome

Risk Factors Associated with Depressive Symptoms in Caregivers of Children with Type 1 Diabetes or Cystic Fibrosis

Objective Evaluate depressive symptoms in caregivers of children with type 1 diabetes (T1D) or cystic fibrosis (CF) and identify associated risk factors. Methods A total of 195 caregivers completed demographic, stress, and depressive symptoms questionnaires. Children’s health status was obtained from medical records. Results Approximately 33% of caregivers reported elevated symptoms of depression (i.e., exceeded clinical cutoff of 16 on the Center for Epidemiological Studies-Depression Scale). For caregivers of children with T1D, elevations were associated with less caregiver education, more family stress, older child age, and worse glycemic control. For caregivers of children with CF, more family stress and lack of employment outside of the home were associated with elevated depressive symptoms. Conclusions Many caregivers of children with T1D or CF experience depressive symptoms, although risk factors may differ in these two populations. Screening of caregiver depressive symptoms as part of routine clinic visits may provide opportunities for needed intervention