The Australasian Resuscitation In Sepsis Evaluation : fluids or vasopressors in emergency department sepsis (ARISE FLUIDS), a multi-centre observational study describing current practice in Australia and New Zealand

Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30-day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6- and 24-h post-enrolment, time to antimicrobial administration, intensive care admission, organ support and in-hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre-enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in-hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Factors influencing cross-border mergers and acquisitions on U.S. firms

Cross-border M&As have become a fundamental characteristic of the global business landscape and has since attracted the attention of both policy makers and academics. Our research attempts to investigate the success probability of a foreign firm acquiring an U.S. firm, identify and understand other underlying non-financial, contributing factors of such cross-border transactions

Necrotising fasciitis during the COVID-19 pandemic: An Australian hospital network experience

Background: The clinical presentations of diseases and the provision of global healthcare services have been negatively affected by the COVID-19 pandemic. Our study aimed to determine the impact of this global pandemic on presentations of necrotising fasciitis (NF). Methods: A retrospective study was conducted of adult patients with NF in South West Sydney Local Health District from January 2017 to October 2022. An analysis of sociodemographic and clinical outcomes was performed comparing the COVID-19 cohort (2020–2022) and the pre-COVID-19 cohort (2017–2019). Results: Sixty-five patients were allocated to the COVID-19 cohort, and 81 patients were in the control cohort. The presentation to hospitals of the COVID-19 cohort was significantly delayed compared to the control cohort (6.1 vs. 3.2 days, P \0.001). Patients of the age group of 40 years and younger experienced prolonged operative time (1.8 vs. 1.0 h, P = 0.040), higher number of operations (4.8 vs. 2.1, P = 0.008), and longer total length of stay (LoS) (31.3 vs. 10.3 days, P = 0.035) during the pandemic. The biochemical, clinical, or post-operative outcomes of two groups were not significantly different. Conclusion: This multi-centre study showed that the COVID-19 pandemic delayed presentations of NF but did not result in any significant overall changes in operative time, ICU admissions, LoS, and mortality rate. Patients aged less than 40 years in the COVID-19 group were likely to experience prolonged operative time, higher number of operations, and greater LoS