Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), but are not good predictors of lung phenotype. Genome-wide association studies (GWAS) previously identified additional genomic sites associated with CF lung disease severity. One of these, at chromosome 11p13, is an intergenic region between Ets homologous factor (EHF) and Apaf-1 interacting protein (APIP). Our goal was to determine the functional significance of this region, which being intergenic is probably regulatory. To identify cis-acting elements, we used DNase-seq and H3K4me1 and H3K27Ac ChIP-seq to map open and active chromatin respectively, in lung epithelial cells. Two elements showed strong enhancer activity for the promoters of EHF and the 5′ adjacent gene E47 like ETS transcription factor 5 (ELF5) in reporter gene assays. No enhancers of the APIP promoter were found. Circular chromosome conformation capture (4C-seq) identified direct physical interactions of elements within 11p13. This confirmed the enhancer-promoter associations, identified additional interacting elements and defined topologically associating domain (TAD) boundaries, enriched for CCCTC-binding factor (CTCF). No strong interactions were observed with the APIP promoter, which lies outside the main TAD encompassing the GWAS signal. These results focus attention on the role of EHF in modifying CF lung disease severity.

Background South Western Sydney (SWS) is a hotspot for diabetes in Australia. We compared intensive care unit (ICU) admission risk between people with and without diabetes admitted to public hospitals in this metropolitan health district. Methods Retrospective study of all admissions to ICU in the New South Wales Admitted Patient Data Collection (APDC) over three years. Data on demographic and health insurance status, primary admission diagnosis, comorbidities including death in admission for public hospital inpatients aged ≥18 years residing in South Western Sydney were analysed. The ICU length of stay was the main outcome variable classified into short stay (≤48hrs) and long stay (>48 hrs) were analysed. Potential predictors were analysed for possible association with long ICU stay among people with and without diabetes admitted to the hospital. Results Of the 187660 inpatients from SWS in the three years, 3.5% spent at least one hour in ICU [5.0% with diabetes versus 3.3% without diabetes, P<0.001]. The median length of ICU stay was similar between people with and without diabetes [40hrs IQR 16-88 hrs versus 43hrs IQR 19-79hrs] as well as the prevalence of long ICU stay [44.9%, 95%CI 42.1, 47.7% versus 43.6%, 95%CI 42.2, 44.9%], respectively. A primary admission diagnosis of circulatory system disease was associated with long ICU stay in both groups, while male sex and a primary diagnosis of nervous system disease was associated with long ICU stay in the non-diabetes group only. Long ICU stay was associated with 1.6 times higher in-hospital mortality in people with diabetes. Conclusions ICU admission was more common in people with diabetes. One in every two admissions to ICU had a long stay, thereby increasing the resource utilization and was associated with higher in-hospital mortality. The predictors identified in the study can target this group to improve resource utilization and efficiency of ICU care. Additional population-based approaches to diabetes care are needed to reduce the risks of acute hospital admission.

Background Long stay in intensive care unit (ICU) is associated with poor outcomes, particularly in people with diabetes. It increases the financial burden of care and this is a challenge to the South Western Sydney region, which is already a hotspot for diabetes in Australia. This study compared ICU admission characteristics of people with and without diabetes and the factors associated with long ICU stay among patients admitted to public hospitals in this metropolitan health district from 2014 to 2017. Methods Cross-sectional datasets on 187,660, including all ICU admissions in the New South Wales Admitted Patient Data Collection (APDC) from June 2014 – July 2017 in public hospital were extracted. Data on demographic and health insurance status, primary admission diagnosis using ICD-10, comorbidities including death among hospital inpatients aged ≥18 years residing in SWS were analysed. The ICU length of stay was the outcome variable and were classified into short stay (≤48 h) and long stay (> 48 h), and were examined against potential confounding factors using bivariate and multiple logistic regression analyses. Results Our results showed higher ICU admissions in patients with diabetes than in those without diabetes (5% vs. 3.3%, P < 0.001) over three years. The median and interquartile range (IQR) of length of the ICU stay were similar in both groups [diabetes: 40 h, IQR = 16–88 h vs. non-diabetes: 43 h, IQR = 19–79 h]. The prevalence of long ICU stays among people with and without diabetes were 44.9% [95% CI 42.1, 47.7%] and 43.6% [95% CI 42.2, 44.9%], respectively. For both groups, increased odds of long ICU stay were associated with death and circulatory system disease admissions, while musculoskeletal disease admissions were associated with lower risk of long ICU stay. In the non-diabetes group, male sex, nervous system disease admissions and living in peri-urban areas were associated with higher odds of long ICU stay. Conclusions The rate of ICU admissions among inpatients remain higher in people with diabetes. One in every two admissions to ICU had a long stay. Additional care for those admitted with circulatory system diseases are needed to reduce long ICU stay related deaths in SWS.