Factors associated with long intensive care unit (ICU) admission among inpatients with and without diabetes in South Western Sydney public hospitals using the New South Wales admission patient data collection (2014-2017).

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.

Regulatory dynamics of 11p13 suggest a role for EHF in modifying CF lung disease severity.

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.

Mechanism of spirometry associated gastro-esophageal reflux in individuals undergoing esophageal assessment.

Persistent variability observed during spirometry, even when technical and personal factors are controlled, has prompted interest in uncovering its underlying mechanisms. Notably, our prior investigations have unveiled that spirometry has the potential to trigger gastro-esophageal reflux in a susceptible population. This current study embarks on elucidating the intricate mechanisms orchestrating reflux induced by spirometry. To achieve this, we enlisted twenty-four (24) participants exhibiting reflux symptoms for esophageal assessment. These participants underwent two sets of spirometry sessions, interspersed with a 10-minute intermission, during which we closely scrutinized fluid flow dynamics and esophageal function through high-resolution impedance esophageal manometry. Our comprehensive evaluation juxtaposed baseline manometric parameters against their equivalents during the initial spirometry session, the intervening rest period, and the subsequent spirometry session. Remarkably, impedance values, serving as a metric for fluid quantity, exhibited a substantial elevation during each spirometry session and the ensuing recovery interval in the pan-esophageal and hypopharyngeal regions when compared to baseline levels. Additionally, the resting pressure of the lower esophageal sphincter experienced a noteworthy reduction subsequent to the first bout of spirometry (13.6 ± 8.8 mmHg) in comparison to the baseline pressure (22.5 ± 13.3 mmHg). Furthermore, our observations unveiled a decline in spirometric parameters-FEV1 (0.14 ± 0.24 L, P = 0.042) and PEFR (0.67 L/s, P = 0.34)-during the second spirometry session when contrasted with the first session. Collectively, our study underscores the compelling evidence that spirometry maneuvers can elicit gastro-esophageal reflux by eliciting intra-esophageal pressure differentials and inducing temporary relaxation of the lower esophageal sphincter.