Intravascular device administration sets: Replacement after standard versus prolonged use in hospitalised patients--a study protocol for a randomised controlled trial (The RSVP Trial)

Introduction Vascular access devices (VADs), such as peripheral or central venous catheters, are vital across all medical and surgical specialties. To allow therapy or haemodynamic monitoring, VADs frequently require administration sets (AS) composed of infusion tubing, fluid containers, pressure-monitoring transducers and/or burettes. While VADs are replaced only when necessary, AS are routinely replaced every 3–4 days in the belief that this reduces infectious complications. Strong evidence supports AS use up to 4 days, but there is less evidence for AS use beyond 4 days. AS replacement twice weekly increases hospital costs and workload. Methods and analysis This is a pragmatic, multicentre, randomised controlled trial (RCT) of equivalence design comparing AS replacement at 4 (control) versus 7 (experimental) days. Randomisation is stratified by site and device, centrally allocated and concealed until enrolment. 6554 adult/paediatric patients with a central venous catheter, peripherally inserted central catheter or peripheral arterial catheter will be enrolled over 4 years. The primary outcome is VAD-related bloodstream infection (BSI) and secondary outcomes are VAD colonisation, AS colonisation, all-cause BSI, all-cause mortality, number of AS per patient, VAD time in situ and costs. Relative incidence rates of VAD-BSI per 100 devices and hazard rates per 1000 device days (95% CIs) will summarise the impact of 7-day relative to 4-day AS use and test equivalence. Kaplan-Meier survival curves (with log rank Mantel-Cox test) will compare VAD-BSI over time. Appropriate parametric or non-parametric techniques will be used to compare secondary end points. p Values of <0.05 will be considered significant.

EVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma

Background We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5–10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12–undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.

Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: Comparing corneal confocal microscopy with intraepidermal nerve fiber density

OBJECTIVE Quantitative assessment of small fiber damage is key to the early diagnosis and assessment of progression or regression of diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve fiber density (IENFD) is the current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has the potential to be a noninvasive and objective image biomarker for identifying small fiber damage. The purpose of this study was to determine the diagnostic performance of CCM and IENFD by using the current guidelines as the reference standard. RESEARCH DESIGN AND METHODS Eighty-nine subjects (26 control subjects and 63 patients with type 1 diabetes), with and without DSPN, underwent a detailed assessment of neuropathy, including CCM and skin biopsy. RESULTS Manual and automated corneal nerve fiber density (CNFD) (P < 0.0001), branch density (CNBD) (P < 0.0001) and length (CNFL) (P < 0.0001), and IENFD (P < 0.001) were significantly reduced in patients with diabetes with DSPN compared with control subjects. The area under the receiver operating characteristic curve for identifying DSPN was 0.82 for manual CNFD, 0.80 for automated CNFD, and 0.66 for IENFD, which did not differ significantly (P = 0.14). CONCLUSIONS This study shows comparable diagnostic efficiency between CCM and IENFD, providing further support for the clinical utility of CCM as a surrogate end point for DSPN.

Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small-cell lung cancer (NSCLC) patients: Results of an open-label, randomized, controlled phase II study (CERTO)

Background: This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v. (CIL-once) or 2×/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary end point was progression-free survival (PFS; independent read); secondary end points included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200. Results: There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P = 0.085]; for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P = 0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvβ3 and αvβ5 expression was neither a predictive nor a prognostic indicator. Conclusions: The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across end points suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment.

End-expiratory lung volume recovers more slowly after closed endotracheal suctioning than after open suctioning : a randomized crossover study

Purpose Endotracheal suctioning causes significant lung derecruitment. Closed suction (CS) minimizes lung volume loss during suction, and therefore, volumes are presumed to recover more quickly postsuctioning. Conflicting evidence exists regarding this. We examined the effects of open suction (OS) and CS on lung volume loss during suctioning, and recovery of end-expiratory lung volume (EELV) up to 30 minutes postsuction. Material and Methods Randomized crossover study examining 20 patients postcardiac surgery. CS and OS were performed in random order, 30 minutes apart. Lung impedance was measured during suction, and end-expiratory lung impedance was measured at baseline and postsuctioning using electrical impedance tomography. Oximetry, partial pressure of oxygen in the alveoli/fraction of inspired oxygen ratio and compliance were collected. Results Reductions in lung impedance during suctioning were less for CS than for OS (mean difference, − 905 impedance units; 95% confidence interval [CI], − 1234 to –587; P < .001). However, at all points postsuctioning, EELV recovered more slowly after CS than after OS. There were no statistically significant differences in the other respiratory parameters. Conclusions Closed suctioning minimized lung volume loss during suctioning but, counterintuitively, resulted in slower recovery of EELV postsuction compared with OS. Therefore, the use of CS cannot be assumed to be protective of lung volumes postsuctioning. Consideration should be given to restoring EELV after either suction method via a recruitment maneuver.

Application of Resilience concept for enhanced management of water supply systems

This paper presents an approach to developing indicators for expressing resilience of a generic water supply system. The system is contextualised as a meta-system consisting of three subsystems to represent the water catchment and reservoir, treatment plant and the distribution system supplying the end-users. The level of final service delivery to end-users is considered as a surrogate measure of systemic resilience. A set of modelled relationships are used to explore relationships between system components when placed under simulated stress. Conceptual system behaviour of specific types of simulated pressure is created for illustration of parameters for indicator development. The approach is based on the hypothesis that an in-depth knowledge of resilience would enable development of decision support system capability which in turn will contribute towards enhanced management of a water supply system. In contrast to conventional water supply system management approaches, a resilience approach facilitates improvement in system efficiency by emphasising awareness of points-of-intervention where system managers can adjust operational control measures across the meta-system (and within subsystems) rather than expansion of the system in entirety in the form of new infrastructure development.

An approach for identifying the limit states of resilience of a water supply system

This paper presents an approach for identifying the limit states of resilience in a water supply system when influenced by different types of pressure (disturbing) forces. Understanding of systemic resilience facilitates identification of the trigger points for early managerial action to avoid further loss of ability to provide satisfactory service availability when the ability to supply water is under pressure. The approach proposed here is to illustrate the usefulness of a surrogate measure of resilience depicted in a three dimensional space encompassing independent pressure factors. That enables visualisation of the transition of the system-state (resilience) between high to low resilience regions and acts as an early warning trigger for decision-making. The necessity of a surrogate measure arises as a means of linking resilience to the identified pressures as resilience cannot be measured directly. The basis for identifying the resilience surrogate and exploring the interconnected relationships within the complete system, is derived from a meta-system model consisting of three nested sub-systems representing the water catchment and reservoir; treatment plant; and the distribution system and end-users. This approach can be used as a framework for assessing levels of resilience in different infrastructure systems by identifying a surrogate measure and its relationship to relevant pressures acting on the system.

A case presenting diagnostic difficulties : making sense of flavivirus serology in the Top End of the Northern Territory

In early April 1998 the Centre for Disease Control (CDC) in Darwin was notified of a case with positive dengue serology. The illness appeared to have been acquired in the Northern Territory (NT). Because dengue is not endemic to the NT, locally acquired infection has significant public health implications, particularly for vector identification and control to limit the spread of infection. Dengue IgM serology was positive on two occasions but the illness was eventually presumptively identified as Kokobera infection. This case illustrates some important points about serology. The interpretation of flavivirus serology is complex and can be misleading, despite recent improvements. The best method of determining the cause of infection is still attempting to reconcile clinical illness details with incubation times and vector presence, as well as laboratory results. This approach ultimately justified the initial period of waiting for confirmatory results in this case, before the institution of public health measures necessary for a true case of dengue.

Head-of-bed elevation improves end-expiratory lung volumes in mechanically ventilated subjects : a prospective observational study

BACKGROUND: Head-of-bed elevation (HOBE) has been shown to assist in reducing respiratory complications associated with mechanical ventilation; however, there is minimal research describing changes in end-expiratory lung volume. This study aims to investigate changes in end-expiratory lung volume in a supine position and 2 levels of HOBE. METHODS: Twenty postoperative cardiac surgery subjects were examined using electrical impedance tomography. End-expiratory lung impedance (EELI) was recorded as a surrogate measurement of end-expiratory lung volume in a supine position and at 20° and then 30°. RESULTS: Significant increases in end-expiratory lung volume were seen at both 20° and 30° HOBE in all lung regions, except the anterior, with the largest changes from baseline (supine) seen at 30°. From baseline to 30° HOBE, global EELI increased by 1,327 impedance units (95% CI 1,080–1,573, P < .001). EELI increased by 1,007 units (95% CI 880–1,134, P < .001) in the left lung region and by 320 impedance units (95% CI 188–451, P < .001) in the right lung. Posterior increases of 1,544 impedance units (95% CI 1,405–1,682, P < .001) were also seen. EELI decreased anteriorly, with the largest decreases occurring at 30° (−335 impedance units, 95% CI −486 to −183, P < .001). CONCLUSIONS: HOBE significantly increases global and regional end-expiratory lung volume; therefore, unless contraindicated, all mechanically ventilated patients should be positioned with HOBE.

Will algorithmic playlist curation be the end of music stardom?

It is 2015 and there are no indications that the relentless digital transformation of the music economy is about to slow down. Rather, the music economy continues to rapidly reinvent itself and industry powers, positions and practices that were redefined only a few years ago are being questioned once again. This paper examines the most recent changes of the music economy as it moves from a product-based towards an access-based logic. The paper starts out by recognising the essential role of technology in the evolution of the music economy. It then moves on to a discussion about the rise of so-called access-based music business models and points out some of the controversies and debates that are associated with these models and online services. With this as a background the paper explores how access-based music services and the algorithmically curated playlists developed by these services transform the relationship between artists, music and fans and challenges the music industrial power relationships and established industry practices once again.

Factors affecting ICT diffusion in Australian construction organisations – the storey from the big end

Our survey findings confirm that 11 factors influence information and communication technology (ICT) diffusion for experienced ICT users. We offer a model that consists of 4 groups of categories: management (M); individual (I); technology (T); and environment (E). Our conclusions reinforce the importance of a coherent ICT diffusion strategy and supportive environment. This requires substantial investment in training and collegial learning support mechanisms. This paper provides an overview of the work undertaken and an analysis of its implications for the construction industry and we provide useful insights that a wide range of construction industry professionals and contractors may find useful.

End-of-life decision making for older people

This chapter deals with the increasing issues surrounding end-of-life decision making. As the life trajectory for older people changes, the need for open discussion about their health problems and treatment becomes more critical. Acceptance of the ageing process itself is often not easy so the matter of a good death is even more distressing for some people to consider. The vignette provides an excellent discussion on the need for open dialogue with the older person and their families, whether they are acutely ill or have chronic health problems. How a person wishes to be treated when quality of life is not going to improve, no matter what interventions are put in place, seems essential for person-centred care. The issue of competency is one that must be determined before any decision is made by any person involved in care.

The Google online marketing challenge and research opportunities

The Google Online Marketing Challenge is an ongoing collaboration between Google and academics, to give students experiential learning. The Challenge gives student teams US$200 in AdWords, Google’s flagship advertising product, to develop online marketing campaigns for actual businesses. The end result is an engaging in-class exercise that provides students and professors with an exciting and pedagogically rigorous competition. Results from surveys at the end of the Challenge reveal positive appraisals from the three—students, businesses, and professors—main constituents; general agreement between students and instructors regarding learning outcomes; and a few points of difference between students and instructors. In addition to describing the Challenge and its outcomes, this article reviews the postparticipation questionnaires and subsequent datasets. The questionnaires and results are publicly available, and this article invites educators to mine the datasets, share their results, and offer suggestions for future iterations of the Challenge.