Factors Associated With All-Cause Rehospitalization and Mortality in Patients with Heart Failure

Abstract Background and Significance: Heart failure is diagnosed in over 5.7 million Americans. Despite substantial scientific advancements in the field of heart failure management this disease continues to be a primary cause of death in 50,000 patients and noted in the death findings of an additional 250,000 individuals annually. Over 6.5 million hospital days and over 668,000 emergency room visits. Depression is prevalent in over 20% of HF patients and in 45% of HF patients following an acute exacerbation of their disease. Purposes: To explore the effect of reactive depression on all-cause rehospitalization and all-cause mortality in NYHA Class III and IV patients during the 12 month following an index hospitalization for HF exacerbation. The study aims were: (a) describe the effect of depression, (b) explain the variance of depression, and (c) determine the moderator effect of depression on patient preparedness to manage complex HF home care all-cause rehospitalization and/or all-cause mortality in HF patients. Theoretical Framework: The Chronic Care Management Theory will guide the study. Methods: Secondary Data Analysis of data obtained from the longitudinal NIH funded SMAC-HF trial. Data Analysis: Descriptive statistics, logistic regression, and multiple linear regression analyses with and with/out interaction effects were performed to address the study purpose and aims. Findings: Descriptive statistics, logistic regression, and multiple linear regression analyses with and with/out interaction effects were performed to address the study purpose and aims. Discussion/Conclusion: Depression as measured by CES-D score greater than 16 has a significant relationship with all-cause rehospitalization p=.09 and all-cause rehospitalization and mortality p=.09. In this study, depression did not demonstrate a relationship with mortality alone. In addition, depression did not have an interaction effect between preparedness and all-cause rehospitalization and/or mortality. Screening for depression should be part of heart failure management. Management of depression may decrease rehospitalization in HF patients

Ideal cardiovascular health in urban Jamaica: Prevalence estimates and relationship to community property value, household assets and educational attainment: A cross-sectional study

Objective Ideal cardiovascular health (ICH) is associated with greater longevity and reduced morbidity, but no research on ICH has been conducted in Jamaica. We aimed to estimate the prevalence of ICH in urban Jamaica and to evaluate associations between ICH and community, household, and individual socioeconomic status (SES). Design Cross-sectional study. Setting Urban communities in Jamaica. Participants 360 men and 665 women who were urban residents aged ≥20 years from a national survey, the Jamaica Health and Lifestyle Survey 2016-2017. Exposures Community SES, using median land values (MLV); household SES, using number of household assets; and individual SES, using education level. Primary outcome The main outcome variable was ICH, defined as having five or more of seven ICH characteristics (ICH-5): current non-smoking, healthy diet, moderate physical activity, normal body mass index, normal blood pressure, normal glucose and normal cholesterol. Prevalence was estimated using weighted survey design and logistic regression models were used to evaluate associations. Results The prevalence of overall ICH (seven characteristics) was 0.51%, while the prevalence of ICH-5 was 22.9% (male 24.5%, female 21.5%, p=0.447). In sex-specific multivariable models adjusted for age, education, and household assets, men in the lower tertiles of community MLV had lower odds of ICH-5 compared with men in the upper tertile (lowest tertile: OR 0.33, 95% CI 0.12 to 0.91, p=0.032; middle tertile: OR 0.46, 95% CI 0.20 to 1.04, p=0.062). Women from communities in the lower and middle tertiles of MLV also had lower odds of ICH-5, but the association was not statistically significant. Educational attainment was inversely associated with ICH-5 among men and positively associated among women. Conclusion Living in poorer communities was associated with lower odds of ICH-5 among men in Jamaica. The association between education level and ICH-5 differed in men and women

Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis

The emerging standard of care for patients with inoperable pancreatic cancer is a combination of cytotoxic drugs gemcitabine and Abraxane, but patient response remains moderate. Pancreatic cancer development and metastasis occur in complex settings, with reciprocal feedback from microenvironmental cues influencing both disease progression and drug response. Little is known about how sequential dual targeting of tumor tissue tension and vasculature before chemotherapy can affect tumor response. We used intravital imaging to assess how transient manipulation of the tumor tissue, or "priming," using the pharmaceutical Rho kinase inhibitor Fasudil affects response to chemotherapy. Intravital Förster resonance energy transfer imaging of a cyclin-dependent kinase 1 biosensor to monitor the efficacy of cytotoxic drugs revealed that priming improves pancreatic cancer response to gemcitabine/Abraxane at both primary and secondary sites. Transient priming also sensitized cells to shear stress and impaired colonization efficiency and fibrotic niche remodeling within the liver, three important features of cancer spread. Last, we demonstrate a graded response to priming in stratified patient-derived tumors, indicating that fine-tuned tissue manipulation before chemotherapy may offer opportunities in both primary and metastatic targeting of pancreatic cancer

Risk Factors for Colorectal Cancer in Patients with Multiple Serrated Polyps: A Cross-Sectional Case Series from Genetics Clinics

Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC). Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps. Methods and Findings We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37%) individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02). For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004) after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes. Conclusion A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.Daniel D. Buchanan, Kevin Sweet, Musa Drini, Mark A. Jenkins, Aung Ko Win, Dallas R. English, Michael D. Walsh, Mark Clendenning, Diane M. McKeone, Rhiannon J. Walters, Aedan Roberts, Sally-Ann Pearson, Erika Pavluk, John L. Hopper, Michael R. Gattas, Jack Goldblatt, Jill George, Graeme K. Suthers, Kerry D. Phillips, Sonja Woodal, Julie Arnold, Kathy Tucker, Amanda Muir, Michael Field, Sian Greening, Steven Gallinger, Renee Perrier, John A. Baron, John D. Potter, Robert Haile, Wendy Franke, Albert de la Chapelle, Finlay Macrae, Christophe Rosty, Neal I. Walker, Susan Parry and Joanne P. Youn

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

Parent attitudes and congenital factors in infant temperament

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Bibliography: leaves 131-133.Not availabl

Quantifying ⁸⁷Sr/⁸⁶Sr temporal stability and spatial heterogeneity for use in tracking fish movement

The specificity and accuracy of inferred fish origin and movement relies on describing spatial heterogeneity and temporal stability of environmental signatures. But the cost and logistics of sample collection often precludes the complete quantification of environmental signature temporal stability and spatial heterogeneity. We used repeated sampling, and a novel approach, Bayesian Ridge Regression (BRR), to quantify the temporal stability and spatial heterogeneity of ⁸⁷Sr/⁸⁶Sr, respectively. We explained 86% of observed variation in ⁸⁷Sr/⁸⁶Sr using a BRR model and estimated ⁸⁷Sr/⁸⁶Sr throughout the Upper North Platte River Basin with high accuracy (±0.00106). Year to year variation in ⁸⁷Sr/⁸⁶Sr signatures ranged from 0.00007 to 0.00073 (SD), while seasonal variation ranged from 0.00091 to 0.00134 (SD). We then assessed the specificity and discussed the accuracy of inferring movement using three scenarios of described spatial heterogeneity. Our results indicate reliable inference of fish movement requires comprehensive quantification of spatial heterogeneity and temporal variation in environmental signatures.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

School Nurses and Telehealth Services as Social Determinant Pathway Disruptors for Youth Diagnosed with Type 1 Diabetes

Type 1 Diabetes (T1D) is the most common chronic disease diagnosed in youth. Individuals living with T1D face a multitude of social determinant disruptors that can result in negative health, and affect the outcomes and quality of their lives. These determinants include environment, economics, food security, social connections, and education. Using the unique position of the school nurse, and coupling this with telehealth services, we can provide children with T1D the necessary tools to improve access to, and quality of their care. By increasing the responsibilities of school nurses and utilizing telehealth more efficiently, we can overcome the social determinant pathway disruptors. This change could increase the likelihood for sustained, positive, and holistic health outcomes related to management and resource availability for chronic disease management. School Nurses can utilize a multidimensional approach to develop a diabetes management and 504 plan, to assist in overcoming common social determinant disruptors faced by children with T1D and their families. Given that historically, funding for school nurses and access to telehealth services is less likely in poor and rural communities as funding is tax based, our group proposes that federal policy is supported to ensure a comprehensive healthcare delivery model which integrates families, providers, and school nurses into the care plan and management. This would require advocating for a restructured federal reimbursement program which will enable healthcare funding streams to reimburse school nursing services that may otherwise be covered in other healthcare settings, including telehealth visits