Risk factors for 3-year-mortality and a tool to screen patient in dialysis population

Introduction: Clinical parameters especially co‑morbidities among end stage renal disease (ESRD) patients are associated with mortality. This study aims to determine the risk factors that are associated with mortality within three years among prevalent patients with ESRD. Methods: This is a cohort study where prevalent ESRD patients’ details were recorded between May 2012 and October 2012. Their records were matched with national death record at the end of year 2015 to identify the deceased patients within three years. Four models were formulated with two models were based on logistic regression models but with different number of predictors and two models were developed based on risk scoring technique. The preferred models were validated by using sensitivity and specificity analysis. Results: A total of 1332 patients were included in the study. Majority succumbed due to cardiovascular disease (48.3%) and sepsis (41.3%). The identified risk factors were mode of dialysis (P < 0.001), diabetes mellitus (P < 0.001), chronic heart disease (P < 0.001) and leg amputation (P = 0.016). The accuracy of four models was almost similar with AUC between 0.680 and 0.711. The predictive models from logistic regression model and risk scoring model were selected as the preferred models based on both accuracy and simplicity. Besides the mode of dialysis, diabetes mellitus and its complications are the important predictors for early mortality among prevalent ESRD patients. Conclusions: The models either based on logistic regression or risk scoring model can be used to screen high risk prevalent ESRD patients

Nitric oxide (NO) elicits aminoglycoside tolerance in Escherichia coli but antibiotic resistance gene carriage and NO sensitivity have not co-evolved

The spread of multidrug-resistance in Gram-negative bacterial pathogens presents a major clinical challenge, and new approaches are required to combat these organisms. Nitric oxide (NO) is a well-known antimicrobial that is produced by the immune system in response to infection, and numerous studies have demonstrated that NO is a respiratory inhibitor with both bacteriostatic and bactericidal properties. However, given that loss of aerobic respiratory complexes is known to diminish antibiotic efficacy, it was hypothesised that the potent respiratory inhibitor NO would elicit similar effects. Indeed, the current work demonstrates that pre-exposure to NO-releasers elicits a >10-fold increase in IC50 for gentamicin against pathogenic E. coli (i.e. a huge decrease in lethality). It was therefore hypothesised that hyper-sensitivity to NO may have arisen in bacterial pathogens, and that this trait could promote the acquisition of antibiotic-resistance mechanisms through enabling cells to persist in the presence of toxic levels of antibiotic. To test this hypothesis, genomics and microbiological approaches were used to screen a collection of E. coli clinical isolates for antibiotic susceptibility and NO tolerance, although the data did not support a correlation between increased carriage of antibiotic resistance genes and NO tolerance. However, the current work has important implications for how antibiotic susceptibility might be measured in future (i.e. +/- NO), and underlines the evolutionary advantage for bacterial pathogens to maintain tolerance to toxic levels of NO