Rapid detection of health-care-associated bloodstream infection in critical care using multipathogen real-time polymerase chain reaction technology: a diagnostic accuracy study and systematic review

Background: There is growing interest in the potential utility of real-time polymerase chain reaction (PCR) in diagnosing bloodstream infection by detecting pathogen deoxyribonucleic acid (DNA) in blood samples within a few hours. SeptiFast (Roche Diagnostics GmBH, Mannheim, Germany) is a multipathogen probe-based system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection. As background to this study, we report a systematic review of Phase III diagnostic accuracy studies of SeptiFast, which reveals uncertainty about its likely clinical utility based on widespread evidence of deficiencies in study design and reporting with a high risk of bias. 

Objective: Determine the accuracy of SeptiFast real-time PCR for the detection of health-care-associated bloodstream infection, against standard microbiological culture. 

Design: Prospective multicentre Phase III clinical diagnostic accuracy study using the standards for the reporting of diagnostic accuracy studies criteria. 

Setting: Critical care departments within NHS hospitals in the north-west of England. 

Participants: Adult patients requiring blood culture (BC) when developing new signs of systemic inflammation. 

Main outcome measures: SeptiFast real-time PCR results at species/genus level compared with microbiological culture in association with independent adjudication of infection. Metrics of diagnostic accuracy were derived including sensitivity, specificity, likelihood ratios and predictive values, with their 95% confidence intervals (CIs). Latent class analysis was used to explore the diagnostic performance of culture as a reference standard. 

Results: Of 1006 new patient episodes of systemic inflammation in 853 patients, 922 (92%) met the inclusion criteria and provided sufficient information for analysis. Index test assay failure occurred on 69 (7%) occasions. Adult patients had been exposed to a median of 8 days (interquartile range 4–16 days) of hospital care, had high levels of organ support activities and recent antibiotic exposure. SeptiFast real-time PCR, when compared with culture-proven bloodstream infection at species/genus level, had better specificity (85.8%, 95% CI 83.3% to 88.1%) than sensitivity (50%, 95% CI 39.1% to 60.8%). When compared with pooled diagnostic metrics derived from our systematic review, our clinical study revealed lower test accuracy of SeptiFast real-time PCR, mainly as a result of low diagnostic sensitivity. There was a low prevalence of BC-proven pathogens in these patients (9.2%, 95% CI 7.4% to 11.2%) such that the post-test probabilities of both a positive (26.3%, 95% CI 19.8% to 33.7%) and a negative SeptiFast test (5.6%, 95% CI 4.1% to 7.4%) indicate the potential limitations of this technology in the diagnosis of bloodstream infection. However, latent class analysis indicates that BC has a low sensitivity, questioning its relevance as a reference test in this setting. Using this analysis approach, the sensitivity of the SeptiFast test was low but also appeared significantly better than BC. Blood samples identified as positive by either culture or SeptiFast real-time PCR were associated with a high probability (> 95%) of infection, indicating higher diagnostic rule-in utility than was apparent using conventional analyses of diagnostic accuracy. 

Conclusion: SeptiFast real-time PCR on blood samples may have rapid rule-in utility for the diagnosis of health-care-associated bloodstream infection but the lack of sensitivity is a significant limiting factor. Innovations aimed at improved diagnostic sensitivity of real-time PCR in this setting are urgently required. Future work recommendations include technology developments to improve the efficiency of pathogen DNA extraction and the capacity to detect a much broader range of pathogens and drug resistance genes and the application of new statistical approaches able to more reliably assess test performance in situation where the reference standard (e.g. blood culture in the setting of high antimicrobial use) is prone to error.

Game-­theoretic Resource Allocation with Real-­time Probabilistic Surveillance Information

Game-theoretic security resource allocation problems have generated significant interest in the area of designing and developing security systems. These approaches traditionally utilize the Stackelberg game model for security resource scheduling in order to improve the protection of critical assets. The basic assumption in Stackelberg games is that a defender will act first, then an attacker will choose their best response after observing the defender’s strategy commitment (e.g., protecting a specific asset). Thus, it requires an attacker’s full or partial observation of a defender’s strategy. This assumption is unrealistic in real-time threat recognition and prevention. In this paper, we propose a new solution concept (i.e., a method to predict how a game will be played) for deriving the defender’s optimal strategy based on the principle of acceptable costs of minimax regret. Moreover, we demonstrate the advantages of this solution concept by analyzing its properties.

Asset Tracking in Critical Power Communications Infrastructures using Passive Techniques

Active network scanning injects traffic into a network and observes responses to draw conclusions about the network. Passive network analysis works by looking at network meta data or by analyzing traffic as it traverses a fixed point on the network. It may be infeasible or inappropriate to scan critical infrastructure networks. Techniques exist to uniquely map assets without resorting to active scanning. In many cases, it is possible to characterize and identify network nodes by passively analyzing traffic flows. These techniques are considered in particular with respect to their application to power industry critical infrastructure.

Understanding informal kinship care: a critical narrative review of theory and research

Many children are cared for on a full-time basis by relatives or adult friends, rather than their biological parents, and often in response to family crises. These kinship care arrangements have received increasing attention from the social science academy and social care professions. However, more information is needed on informal kinship care that is undertaken without official ratification by welfare agencies and often unsupported by the state. This article presents a comprehensive, narrative review of international, research literature on informal, kinship care to address this gap. Using systematic search and review protocols, it synthesises findings regarding: (i) the way that informal kinship care is defined and conceptualised; (ii) the needs of the carers and children; and (iii) ways of supporting this type of care. A number of prominent themes are highlighted including the lack of definitional clarity; the various adversities experienced by the families; and the requirement to understand the interface between formal and informal supports. Key messages are finally identified to inform the development of family friendly policies, interventions, and future research.

Critical Nodes In Directed Networks

Critical nodes—or “middlemen”—have an essential place in both social and economic networks when considering the flow of information and trade. This paper extends the concept of critical nodes to directed networks and in doing so identify strong and weak middlemen.
Node contestability is introduced as a form of competition in networks; a duality between uncontested intermediaries and middlemen is established. The brokerage power of middlemen is formally expressed and a general algorithm is constructed to measure the brokerage power of each node from the networks adjacency matrix. Augmentations of the brokerage power measure are discussed to encapsulate relevant centrality measures. Furthermore, we extend these notions and provide measures of the competitiveness of a network.
We use these concepts to identify and measure middlemen in two empirical socio-economic networks, the elite marriage network of Renaissance Florence and Krackhardt’s advice net- work.

Developing an information booklet to meet the needs of intensive care patients and relatives

Changes in the economic climate and the delivery of health care require that pre-operative information programmes are effective and efficiently implemented. In order to be effective the pre-operative programme must meet the information needs of intensive care unit (ICU) patients and their relatives. Efficiency can be achieved through a structured pre-operative programme which provides a framework for teaching. The need to develop an ICU information booklet in a large teaching hospital in Northern Ireland has become essential to provide relevant information and improve the quality of service for patients and relatives, as set out in the White Paper, ‘Working for Patients’, (DoH, 1989). The first step in establishing a patient education programme was to ascertain patients' and relatives' informational needs. A ‘needs assessment’ identified the pre-operative information needs of ICU patients and their relatives (McGaughey, 1994) and the findings were used to plan and publish an information booklet. The ICU booklet provides a structure for pre-operative visits to ensure that patients and relatives information needs are met.

Realist synthesis: Critical care rapid response systems.

Background Rapid Response Systems (RRS) consist of four interrelated and interdependent components; an event detection and trigger mechanism, a response strategy, a governance structure and process improvement system. These multiple components of the RRS pose problems in evaluation as the intervention is complex and cannot be evaluated using a traditional systematic review. Complex interventions in healthcare aimed at changing service delivery and related behaviour of health professionals require a different approach to summarising the evidence. Realist synthesis is such an approach to reviewing research evidence on complex interventions to provide an explanatory analysis of how and why an intervention works or doesn’t work in practice. The core principle is to make explicit the underlying assumptions about how an intervention is suppose to work (ie programme theory) and then use this theory to guide evaluation. Methods A realist synthesis process was used to explain those factors that enable or constrain the success of RRS programmes. Results The findings from the review include the articulation of the RRS programme theories, evaluation of whether these theories are supported or refuted by the research evidence and an evaluation of evidence to explain the underlying reasons why RRS works or doesn’t work in practice. Rival conjectured RRS programme theories were identified to explain the constraining factors regarding implementation of RRS in practice. These programme theories are presented using a logic model to highlight all the components which impact or influence the delivery of RRS programmes in the practice setting. The evidence from the realist synthesis provided the foundation for the development of hypothesis to test and refine the theories in the subsequent stages of the Realist Evaluation PhD study [1]. This information will be useful in providing evidence and direction for strategic and service planning of acute care to improve patient safety in hospital. References: McGaughey J, Blackwood B, O’Halloran P, Trinder T. J. & Porter S. (2010) Realistic Evaluation of Early Warning Systems and the Acute Life-threatening Events – Recognition and Treatment training course for early recognition and management of deteriorating ward-based patients: research protocol. Journal of Advanced Nursing 66 (4), 923-932.

Building Information Modelling (BIM) Software Interoperability: A Review of the Construction Sector

Building Information Modelling (BIM) is continuing to evolve and develop as the construction industry progresses towards level 2 maturity. However, one of the core barriers in this progression is the aspect of interoperability between software packages. This research and paper stems from a Knowledge Transfer Partnership (KTP) where both industry and academia come together to address this shortcoming within the sector. One of the core objectives of this partnership and the aim of this study is investigating potential solutions to this barrier, while also developing best working practices to be applied in industry. Using one of the case studies from this partnership (a temporary steel structure), this paper demonstrates a potential solution to addressing interoperability within structural analysis and detailing packages, MasterSeries and Revit respectively. The findings of the research indicate that a process based approach rather than that of additional software coding as being the preferred solution. The results of this preliminary research will aid in the development of the topic of interoperability within the sector, while also developing the knowledge and competencies of the parties within the KTP. The findings are explored further, by providing an overview of the resolution process adopted in this case study, in overcoming the interoperability that arose as the project progressed. It is envisaged that this study will assist the construction sector and its adoption of BIM technologies, while also addressing the critical aspect of operability between software.

A Novel Approach for Axle Detection in Bridge Weigh-In-Motion Systems

Bridge weigh-in-motion (B-WIM), a system that uses strain sensors to calculate the weights of trucks passing on bridges overhead, requires accurate axle location and speed information for effective performance. The success of a B-WIM system is dependent upon the accuracy of the axle detection method. It is widely recognised that any form of axle detector on the road surface is not ideal for B-WIM applications as it can cause disruption to the traffic (Ojio & Yamada 2002; Zhao et al. 2005; Chatterjee et al. 2006). Sensors under the bridge, that is Nothing-on-Road (NOR) B-WIM, can perform axle detection via data acquisition systems which can detect a peak in strain as the axle passes. The method is often successful, although not all bridges are suitable for NOR B-WIM due to limitations of the system. Significant research has been carried out to further develop the method and the NOR algorithms, but beam-and-slab bridges with deep beams still present a challenge. With these bridges, the slabs are used for axle detection, but peaks in the slab strains are sensitive to the transverse position of wheels on the beam. This next generation B-WIM research project extends the current B-WIM algorithm to the problem of axle detection and safety, thus overcoming the existing limitations in current state-of–the-art technology. Finite Element Analysis was used to determine the critical locations for axle detecting sensors and the findings were then tested in the field. In this paper, alternative strategies for axle detection were determined using Finite Element analysis and the findings were then tested in the field. The site selected for testing was in Loughbrickland, Northern Ireland, along the A1 corridor connecting the two cities of Belfast and Dublin. The structure is on a central route through the island of Ireland and has a high traffic volume which made it an optimum location for the study. Another huge benefit of the chosen location was its close proximity to a nearby self-operated weigh station. To determine the accuracy of the proposed B-WIM system and develop a knowledge base of the traffic load on the structure, a pavement WIM system was also installed on the northbound lane on the approach to the structure. The bridge structure selected for this B-WIM research comprised of 27 pre-cast prestressed concrete Y4-beams, and a cast in-situ concrete deck. The structure, a newly constructed integral bridge, spans 19 m and has an angle of skew of 22.7°.