Active Surveillance of Candidemia, Australia

This infection has a high death rate and is predominantly associated with healthcare

Risk factors for peripheral intravenous catheter failure: a multivariate analysis of data from a randomized controlled trial

Objective.To assess the relative importance of independent risk factors for peripheral intravenous catheter (PIVC) failure.Methods.Secondary data analysis from a randomized controlled trial of PIVC dwell time. The Prentice, Williams, and Peterson statistical model was used to identify and compare risk factors for phlebitis, occlusion, and accidental removal.Setting.Three acute care hospitals in Queensland, Australia.Participants.The trial included 3,283 adult medical and surgical patients (5,907 catheters) with a PIVC with greater than 4 days of expected use.Results.Modifiable risk factors for occlusion included hand, antecubital fossa, or upper arm insertion compared with forearm (hazard ratio [HR], 1.47 [95% confidence interval (CI), 1.28--1.68], 1.27 [95% CI, 1.08--1.49], and 1.25 [95% CI, 1.04--1.50], respectively); and for phlebitis, larger diameter PIVC (HR, 1.48 [95% CI, 1.08--2.03]). PIVCs inserted by the operating and radiology suite staff had lower occlusion risk than ward insertions (HR, 0.80 [95% CI, 0.67--0.94]). Modifiable risks for accidental removal included hand or antecubital fossa insertion compared with forearm (HR, 2.45 [95% CI, 1.93--3.10] and 1.65 [95% CI, 1.23--2.22], respectively), clinical staff insertion compared with intravenous service (HR, 1.69 [95% CI, 1.30--2.20]); and smaller PIVC diameter (HR, 1.29 [95% CI, 1.02--1.61]). Female sex was a nonmodifiable factor associated with an increased risk of both phlebitis (HR, 1.64 [95% CI, 1.28--2.09]) and occlusion (HR, 1.44 [95% CI, 1.30--1.61]).Conclusions.PIVC survival is improved by preferential forearm insertion, selection of appropriate PIVC diameter, and insertion by intravenous teams and other specialists.Trial registration.The original randomized controlled trial on which this secondary analysis is based is registered with the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au; ACTRN12608000445370)

Needleless connector decontamination for prevention of central venous access device infection: A pilot randomized controlled trial

Pilot randomized controlled trial (180 patients) of needleless connector decontamination. Central line-associated bloodstream infection occurred in 2% (1/61) of 70% isopropyl alcohol (IPA) wipe, 2% (1/59) of 70% IPA cap, and zero (0/58) infections in 2% chlorhexidine gluconate in 70% IPA wipe patients. Larger definitive trials are feasible and needed

Dressings and securements for the prevention of peripheral intravenous catheter failure in adults (SAVE): a pragmatic, randomised controlled, superiority trial

Background: Two billion peripheral intravenous catheters (PIVCs) are used globally each year, but optimal dressing and securement methods are not well established. We aimed to compare the efficacy and costs of three alternative approaches to standard non-bordered polyurethane dressings. Methods: We did a pragmatic, randomised controlled, parallel-group superiority trial at two hospitals in Queensland, Australia. Eligible patients were aged 18 years or older and required PIVC insertion for clinical treatment, which was expected to be required for longer than 24 h. Patients were randomly assigned (1:1:1:1) via a centralised web-based randomisation service using random block sizes, stratified by hospital, to receive tissue adhesive with polyurethane dressing, bordered polyurethane dressing, a securement device with polyurethane dressing, or polyurethane dressing (control). Randomisation was concealed before allocation. Patients, clinicians, and research staff were not masked because of the nature of the intervention, but infections were adjudicated by a physician who was masked to treatment allocation. The primary outcome was all-cause PIVC failure (as a composite of complete dislodgement, occlusion, phlebitis, and infection [primary bloodstream infection or local infection]). Analysis was by modified intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000769987. Findings: Between March 18, 2013, and Sept 9, 2014, we randomly assigned 1807 patients to receive tissue adhesive with polyurethane (n=446), bordered polyurethane (n=454), securement device with polyurethane (n=453), or polyurethane (n=454); 1697 patients comprised the modified intention-to-treat population. 163 (38%) of 427 patients in the tissue adhesive with polyurethane group (absolute risk difference −4·5% [95% CI −11·1 to 2·1%], p=0·19), 169 (40%) of 423 of patients in the bordered polyurethane group (–2·7% [–9·3 to 3·9%] p=0·44), 176 (41%) of 425 patients in the securement device with poplyurethane group (–1·2% [–7·9% to 5·4%], p=0·73), and 180 (43%) of 422 patients in the polyurethane group had PIVC failure. 17 patients in the tissue adhesive with polyurethane group, two patients in the bordered polyurethane group, eight patients in the securement device with polyurethane group, and seven patients in the polyurethane group had skin adverse events. Total costs of the trial interventions did not differ significantly between groups. Interpretation: Current dressing and securement methods are commonly associated with PIVC failure and poor durability, with simultaneous use of multiple products commonly required. Cost is currently the main factor that determines product choice. Innovations to achieve effective, durable dressings and securements, and randomised controlled trials assessing their effectiveness are urgently needed

Integrative genomic and proteomic analyses identify targets for Lkb1 deficient metastatic lung tumors

SummaryIn mice, Lkb1 deletion and activation of KrasG12D results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1 deficient primary and metastatic lung tumors and that the combined inhibition of SRC, PI3K and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathways that may be targeted for treatment

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Determinants of mortality in non-neutropenic ICU patients with candidaemia

Introduction: Candidaemia in critically-ill intensive care unit (ICU) patients is associated with high crude mortality. Determinants of mortality – particularly those amenable to potential modification – are incompletely defined. Methods: A nationwide prospective clinical and microbiological cohort study of all episodes of ICU-acquired candidaemia occurring in non-neutropenic adults was undertaken in Australian ICUs between 2001 and 2004. Multivariate Cox regression analyses were performed to determine independently significant variables associated with mortality. Results: 183 episodes of ICU-acquired candidaemia occurred in 183 patients during the study period. Of the 179 with microbiological data, Candida albicans accounted for 111 (62%) episodes and Candida glabrata, 32 (18%). Outcome data were available for 173: crude hospital mortality at 30 days was 56%. Host factors (older age, ICU admission diagnosis, mechanical ventilation and ICU admission diagnosis) and failure to receive systemic antifungal therapy were significantly associated with mortality on multivariate analysis. Among the subset who received initial fluconazole therapy (n = 93), the crude mortality was 52%. Host factors (increasing age and haemodialysis receipt), but not organism- (Candida species, fluconazole MIC), pharmacokinetic- (fluconazole dose, time to initiation), or pharmacodynamic-related parameters (fluconazole dose:MIC ratio) were associated with mortality. Process of care measures advocated in recent guidelines were implemented inconsistently: follow-up blood cultures were obtained in 68% of patients, central venous catheters removed within five days in 80% and ophthalmological examination performed in 36%. Conclusions: Crude mortality remains high in Australian ICU patients with candidaemia and is overwhelmingly related to host factors but not treatment variables (the time to initiation of antifungals or fluconazole pharmacokinetic and pharmacodynamic factors). The role and timing of early antifungal intervention in critically-ill ICU patients requires further investigation.Deborah J.E. Marriott, E. Geoffrey Playford, Sharon Chen, Monica Slavin, Quoc Nguyen, David Ellis and Tania C. Sorrell for the Australian Candidaemia Stud

Evaluation of the ICT Malaria P.f/P.v and the OptiMal Rapid Diagnostic Tests for Malaria in Febrile Returned Travellers

Rapid diagnostic tests (RDTs) are less reliant on expert microscopy and have the potential to reduce errors in malaria diagnosis but have not been extensively evaluated in nonimmune persons or in countries where infection is not endemic. We evaluated the ICT P.f/P.v (ICT-Amrad, Sydney, Australia) and OptiMal (Flow Inc., Portland, Oreg.) assays prospectively for the diagnosis of malaria in 158 specimens from 144 febrile returned travellers in Australia by using expert microscopy and PCR as reference standards. Malaria was diagnosed in 93 specimens from 87 patients by expert microscopy, with 3 additional specimens from recently treated patients testing positive for Plasmodium falciparum by PCR. For the diagnosis of asexual-stage P. falciparum malaria, the sensitivity and specificity of the ICT P.f/P.v assay were 97 and 90%, respectively, and those of the OptiMal assay were 85 and 96%, respectively. The ICT P.f/P.v assay missed one infection with a density of 45 parasites/μl, whereas the OptiMal assay missed infections up to 2,500/μl; below 1,000/μl, its sensitivity was only 43%. For the diagnosis of P. vivax malaria, the sensitivity and specificity of the ICT P.f/P.v assay were 44 and 100%, respectively, and those of the OptiMal assay were 80 and 97%, respectively. Both assays missed infections with parasite densities over 5,000/μl: up to 10,000/μl with the former and 5,300/μl with the latter. Despite the high sensitivity of the ICT P.f/P.v assay for P. falciparum malaria, caution is warranted before RDTs are widely adopted for the diagnosis of malaria in nonimmune patients or in countries where malaria is not endemic

Sections on some spores from the Lower Carboniferous of Spitsbergen

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Parenteral nutrition-associated bloodstream infection in an Australian teaching hospital-an 8-year retrospective study of over 11,000 PN-days

Background: Bloodstream infections (BSIs) are a well-recognized complication of parenteral nutrition (PN). However, their epidemiology and clinical consequences are incompletely described. Methods: A retrospective cohort study was performed, from 2002 to 2009, of all hospital inpatients who were administered PN, outside the intensive care setting, at a major tertiary hospital in Queensland, Australia. Results: In 780 episodes of PN administration, 120 BSIs occurred, giving an incidence of 10.0/1000 PN-days. The majority of PN-associated BSIs were classified as central line-associated (n = 98, 81.7%). Candida spp. were the most frequent pathogens. Observed BSI management revealed that over 8% of intravascular devices were inappropriately retained, over 30% of empirical antibiotic therapy was inappropriate, and 62% of antifungal therapy was delayed >= 48 h. All-cause hospital mortality was over 2-fold greater in patients with a PN-associated BSI compared to those without (17.9% vs 8.3%, crude odds ratio (OR) 2.4, 95% confidence interval (CI) 1.29-4.35, p = 0.002). BSI was identified as an independent risk factor for mortality (adjusted OR 3.54, 95% CI 1.76-7.12, p < 0.001). Low baseline albumin levels and a requirement for intravenous insulin infusion (a marker of sustained hyperglycaemia) were independent risk factors for the development of PN-associated BSIs. Conclusions: PN-associated BSI in hospital inpatients is common and is associated with mortality. The implementation of standardized evidence-based infection prevention strategies, particularly targeting IVD maintenance, is a priority. PN-associated BSI management pathways require optimization, with timely IVD removal and appropriate antimicrobial therapy. Depending on local epidemiology patterns, empirical antifungal therapy should be considered