Nepean Hospital

About: Nepean Hospital is a healthcare organization based out in Penrith, New South Wales, Australia. It is known for research contribution in the topics: Intensive care & Population. The organization has 1088 authors who have published 1314 publications receiving 31401 citations.

IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy

Abstract: Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.

Intensity of continuous renal-replacement therapy in critically ill patients.

Abstract: Background The optimal intensity of continuous renal-replacement therapy remains unclear. We conducted a multicenter, randomized trial to compare the effect of this therapy, delivered at two different levels of intensity, on 90-day mortality among critically ill patients with acute kidney injury. Methods We randomly assigned critically ill adults with acute kidney injury to continuous renal-replacement therapy in the form of postdilution continuous venovenous hemodiafiltration with an effluent flow of either 40 ml per kilogram of body weight per hour (higher intensity) or 25 ml per kilogram per hour (lower intensity). The primary outcome measure was death within 90 days after randomization. Results Of the 1508 enrolled patients, 747 were randomly assigned to higher-intensity therapy, and 761 to lower-intensity therapy with continuous venovenous hemodiafiltration. Data on primary outcomes were available for 1464 patients (97.1%): 721 in the higher-intensity group and 743 in the lower-intensity group. The two study groups had similar baseline characteristics and received the study treatment for an average of 6.3 and 5.9 days, respectively (P = 0.35). At 90 days after randomization, 322 deaths had occurred in the higher-intensity group and 332 deaths in the lower-intensity group, for a mortality of 44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P = 0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P = 0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P Conclusions In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days. (ClinicalTrials.gov number, NCT00221013.)

Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis

Abstract: Procalcitonin is widely reported as a useful biochemical marker to diff erentiate sepsis from other non-infectious causes of systemic infl ammatory response syndrome. In this systematic review, we estimated the diagnostic accuracy of procalcitonin in sepsis diagnosis in critically ill patients. 18 studies were included in the review. Overall, the diagnostic performance of procalcitonin was low, with mean values of both sensitivity and specifi city being 71% (95% CI 67–76) and an area under the summary receiver operator characteristic curve of 0·78 (95% CI 0·73–0·83). Studies were grouped into phase 2 studies (n=14) and phase 3 studies (n=4) by use of Sackett and Haynes’ classifi cation. Phase 2 studies had a low pooled diagnostic odds ratio of 7·79 (95% CI 5·86–10·35). Phase 3 studies showed signifi cant heterogeneity because of variability in sample size (meta-regression coeffi cient –0·592, p=0·017), with diagnostic performance upwardly biased in smaller studies, but moving towards a null eff ect in larger studies. Procalcitonin cannot reliably diff erentiate sepsis from other non-infectious causes of systemic infl ammatory response syndrome in critically ill adult patients. The fi ndings from this study do not lend support to the widespread use of the procalcitonin test in critical care settings.