In Alabama, Dear, With You

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Value of Community Partnership for Understanding Stress and Coping in Rural Yup’ik Communities: The CANHR Study

Stress and trauma can compromise physical and mental health. Rural Alaska Native communities have voiced concern about stressful and traumatic events and their effects on health. The goal of the Yup’ik Experiences of Stress and Coping Project is to develop an in-depth understanding of experiences of stress and ways of coping in Yup’ik communities. The long-range goal is to use project findings to develop and implement a community-informed and culturally grounded intervention to reduce stress and promote physical and mental health in rural Alaska Native communities. This paper introduces a long-standing partnership between the Yukon-Kuskokwim Regional Health Corporation, rural communities it serves, and the Center for Alaska Native Health Research at the University of Alaska Fairbanks. Within the context of the Stress and Coping project, we then discuss the value and challenges of taking a CBPR approach to advance science and address a priority community concern, and share strategies to respond to challenges. Focus groups were conducted to culturally adapt an existing structured interview and daily diary protocol to better fit Yup’ik ways of knowing. As modified, these interviews increased understanding of stress and coping particular to two Yup’ik communities. Challenges included the geographical nature of Yup’ik communities, communication barriers, competing priorities, and confidentiality issues. Community participation was central in the development of the study protocol, helped ensure that the research was culturally appropriate and relevant to the community, and facilitated access to participant knowledge and rich data to inform intervention development

The model of mortality with incident cirrhosis (MoMIC) and the model of long-term outlook of mortality in dcirrhosis (LOMiC)

The purpose of this study was to produce two statistical survival models in those with cirrhosis utilising only routine parameters, including non-liver-related clinical factors that influence survival. The first model identified and utilised factors impacting short-term survival to 90-days post incident diagnosis, and a further model characterised factors that impacted survival following this acute phase. Data were from the Clinical Practice Research Datalink linked with Hospital Episode Statistics. Incident cases in patients ≥18 years were identified between 1998 and 2014. Patients that had prior history of cancer or had received liver transplants prior were excluded. Model-1 used a logistic regression model to predict mortality. Model-2 used data from those patients who survived 90 days, and used an extension of the Cox regression model, adjusting for time-dependent covariables. At 90 days, 23% of patients had died. Overall median survival was 3.7 years. Model-1: numerous predictors, prior comorbidities and decompensating events were incorporated. All comorbidities contributed to increased odds of death, with renal disease having the largest adjusted odds ratio (OR = 3.35, 95%CI 2.97–3.77). Model-2: covariables included cumulative admissions for liver disease-related events and admissions for infections. Significant covariates were renal disease (adjusted hazard ratio (HR = 2.89, 2.47–3.38)), elevated bilirubin levels (aHR = 1.38, 1.26–1.51) and low sodium levels (aHR = 2.26, 1.84–2.78). An internal validation demonstrated reliability of both models. In conclusion: two survival models that included parameters commonly recorded in routine clinical practice were generated that reliably forecast the risk of death in patients with cirrhosis: in the acute, post diagnosis phase, and following this critical, 90 day phase. This has implications for practice and helps better forecast the risk of mortality from cirrhosis using routinely recorded parameters without inputs from specialists

Disseminating Research in Rural Yup’ik Communities: Challenges and Ethical Considerations in Moving from Discovery to Intervention Development in the Translational Pathway

The native people of Alaska have experienced historical trauma and on-going rapid, often externally imposed changes in culture and lifestyle patterns. As a consequence, these populations shoulder a disproportionately high burden of psychological stress. Yup\u27ik communities in the Yukon Kuskokwim Delta region in Southwest Alaska have experienced epidemics and forced acculturation, contributing to behavioural health issues, including substance abuse and suicide. Cultural loss in Yup\u27ik communities has resulted in generational gaps that disrupt the transmission of cultural traditions and values important for well-being. Despite these intrusions, Yup\u27ik communities have retained cultural traditions which act as protective factors against the development of physical and psychological illness. These cultural protective factors can be harnessed to collaboratively develop culturally grounded interventions that reduce stress and build connections across generations, helping communities move towards wellness on their own terms

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

The impact on hospital resource utilisation of treatment of hepatic encephalopathy with rifaximin-α

BACKGROUND & AIMS: Rifaximin-α reduces the risk of recurrence of overt hepatic encephalopathy. However, there remain concerns regarding the financial cost of the drug. We aimed to study the impact of treatment with rifaximin-α on healthcare resource utilisation using data from seven UK liver treatment centres. METHODS: All seven centres agreed a standardised data set and data characterising clinical, demographic and emergency hospital admissions were collected retrospectively for the time periods 3, 6 and 12 months before and following initiation of rifaximin-α. Admission rates and hospital length of stay before and during therapy were compared. Costs of admissions and drug acquisition were estimated using published sources. Multivariate analyses were carried out to assess the relative impact of various factors on hospital length of stay. RESULTS: Data were available from 326 patients. Following the commencement of rifaximin, the total hospital length of stay reduced by an estimated 31-53%, equating to a reduction in inpatient costs of between £4858 and £6607 per year. Taking into account drug costs of £3379 for 1-year treatment with rifaximin-α, there was an estimated annual mean saving of £1480-£3228 per patient. CONCLUSIONS: Initiation of treatment with rifaximin-α was associated with a marked reduction in the number of hospital admissions and hospital length of stay. These data suggest that treatment of patients with rifaximin-α for hepatic encephalopathy was generally cost saving