i-STAT – Combining Chemistry and Haematology in PoCT

Point-of-care testing (PoCT) is traditionally considered a branch or offshoot of clinical chemistry. The appearance on the market of small, light, inexpensive, multi-purpose, point-of-care analysers, which combine a number of widely differing analytes, has to some degree upset this paradigm. Such analysers, however, are invaluable in some clinical settings.Specialties other than clinical chemistry may have differing views on traditional test management, particularly with regard to quality control (QC), quality assurance (QA), and training. These views must be considered when designing an overall PoCT management plan. Test management issues should be resolved by taking the view that it is a ‘point-of-care’ test, and by looking at the specific test technology and method involved, rather than by just assuming it is a ‘haematology’ or a ‘chemistry’ test.Clinical users of a combined PoCT system are principally interested in the generation of good quality results. To avoid confusion, any advice given to clinical staff regarding their analysers should be clear, concise, and above all else, consistent.     

The Evidence to Support Point-of-Care Testing

Point-of-care testing (PoCT) is now possible in many areas of clinical medicine. This review examines the evidence for its application in four areas: self-monitoring; community testing primarily in the pharmacy; general practice; and the emergency department. In all of these areas except pharmacy, randomised controlled trials of PoCT versus central laboratory testing have been performed, with the results of some of these trials supporting the use of PoCT. Aside from providing evidence, these trials and other observational studies have provided valuable information about how PoCT should be conducted. In particular they have shown that adoption of the technology is often insufficient to achieve a benefit and in some cases a change of care process is also required.     

Investigation of the effect of Interleukin-1 receptor antagonist (IL-1ra) on markers of inflammation in non-ST elevation acute coronary syndromes (The MRC-ILA-HEART Study)

Background

Point of care testing (PoCT) may be a useful adjunct in the management of chronic conditions in general practice (GP). The provision of pathology test results at the time of the consultation could lead to enhanced clinical management, better health outcomes, greater convenience and satisfaction for patients and general practitioners (GPs), and savings in costs and time. It could also result in inappropriate testing, increased consultations and poor health outcomes resulting from inaccurate results. Currently there are very few randomised controlled trials (RCTs) in GP that have investigated these aspects of PoCT.

Design/Methods

The Point of Care Testing in General Practice Trial (PoCT Trial) was an Australian Government funded multi-centre, cluster randomised controlled trial to determine the safety, clinical effectiveness, cost effectiveness and satisfaction of PoCT in a GP setting. The PoCT Trial covered an 18 month period with the intervention consisting of the use of PoCT for seven tests used in the management of patients with diabetes, hyperlipidaemia and patients on anticoagulant therapy. The primary outcome measure was the proportion of patients within target range, a measure of therapeutic control. In addition, the PoCT Trial investigated the safety of PoCT, impact of PoCT on patient compliance to medication, stakeholder satisfaction, cost effectiveness of PoCT versus laboratory testing, and influence of geographic location.

Discussion

The paper provides an overview of the Trial Design, the rationale for the research methodology chosen and how the Trial was implemented in a GP environment. The evaluation protocol and data collection processes took into account the large number of patients, the broad range of practice types distributed over a large geographic area, and the inclusion of pathology test results from multiple pathology laboratories. The evaluation protocol developed reflects the complexity of the Trial setting, the Trial Design and the approach taken within the funding provided. The PoCT Trial is regarded as a pragmatic RCT, evaluating the effectiveness of implementing PoCT in GP and every effort was made to ensure that, in these circumstances, internal and external validity was maintained.

Trial Registration

12612605000272695     

Point-of-Care Testing and Creatinine Measurement

This paper reviews the current status of point-of-care testing (PoCT) devices that are available for measuring whole blood or serum/plasma creatinine globally and within Australasia. Information on non-analytical specifications and analytical performance is provided using data sourced from recently published literature, external quality assurance programs and evaluative work by the author's unit. The limitations of current devices are summarised.     

Evolution of Point-of-Care Testing in Australia

Currently no mandatory standards or guidelines exist for Point-of-Care Testing (PoCT) in Australia. In 2001, a report on the role and value of ‘near patient testing’ in general practice outlined work that was required to assist the Australian Government to decide how to manage PoCT. Phillips Fox reported that adoption of mandatory accreditation requirements was not justified by the level of risk associated with PoCT.If implemented appropriately, PoCT could be useful with frontline management of chronic disease, relieving stress on general practice and expanding the reach of pathology.Interim PoCT standards in general practice were developed by a Quality Use of Pathology committee, and formed an accreditation framework for the PoCT in General Practice Trial. This trial concluded that PoCT has a role in supporting the primary healthcare team to manage chronic disease patients.While results of the trial are still being considered, the potential impact of funding PoCT in general practice is being treated as part of the wider review of pathology funding currently taking place in Australia.Although Australia has local models from which to draw experience, it has yet to decide the quality framework it would adopt if it was to roll out PoCT in general practice. The quality framework that Australia adopts for PoCT must achieve high quality pathology results that enhance clinical care.     

Integrating PoCT into Clinical Care

In South Australia, the Integrated Cardiovascular Clinical Network SA (iCCnet SA) is the provider which enacts the recommendations and policies of the state-wide cardiac clinical network working parties in rural and remote areas by developing appropriate clinical tools.Pathology tests play a significant role in contributing to best practice for patient diagnosis and management. As most South Australian country hospitals do not have timely access to pathology results, point-of-care testing (PoCT) for troponin and N-terminal pro-brain natriuretic peptide (NT-proBNP) has been integrated into clinical pathways for the management of possible acute coronary syndrome (ACS) and suspected heart failure patients respectively. Compared with control hospitals of similar size and resources, preliminary results from an iCCnet SA regional hospital showed improved patient outcomes for ACS: 30-day readmission rates were reduced from 10.4% to 4.2% (p = 0.03) and there was a corresponding trend in the reduction of in-hospital death rates from 15.8% to 9.8% (p = 0.1).The establishment of iCCnet SA has improved outcomes for rural patients presenting to hospital with symptoms suggestive of ACS by facilitating the uptake of evidence-based acute cardiac care. Implementation of PoCT equipment into clinical care requires a systematic approach that engages all stakeholders involved in patient care. Provider clinical networks, such as iCCnet SA, provide a structure for effective working relationships between health professionals. PoCT has been critical to the success of the network, but it needs to be implemented within an integrated system of care to produce optimal outcomes.     

The National QAAMS Program – A Practical Example of PoCT Working in the Community

The Quality Assurance for Aboriginal and Torres Strait Islander Medical Services (QAAMS) Program is the largest and longest-standing national point-of-care testing (PoCT) program in Australia. With a focus on PoCT for diabetes management, it now operates in 115 Indigenous medical services and has been funded continuously by the Australian Government for 11 years. A recent independent evaluation of the QAAMS Program concluded that the program continues to meet best practice standards for Indigenous healthcare, diabetes management and PoCT.     

Alternative strategies in assuring blood safety: An Overview

Assuring transfusion safety is an essential element of health care in all countries, requiring government commitment, national policy and a legal framework. Fundamental safety strategies include selection of low risk donors, Good Manufacturing Practices in preparation of blood components, and appropriate clinical use including avoidance of unnecessary transfusions. Hemovigilance, including surveillance for known adverse events and sentinel reporting of unexpected adverse events, enhances safety through benchmarking to promote best practices and by enabling rapid responses to new threats. Preventing transmission of infectious diseases is a principal safety concern. Selection of low risk donors includes use of screening questions to elicit risk factors known to be associated with transmissible infections. Laboratory testing for specific infectious disease markers is an established strategy for interdicting contaminated donations. The sensitivity, specificity, and operational convenience of laboratory testing have improved over time and newer technologies are imminent. Donor screening and laboratory testing, while highly effective in reducing risk, cannot eliminate all risk from known agents and must be developed de novo to address emerging infections. In contrast, pathogen reduction technologies offer the possibility for robust inactivation of a broad spectrum of blood transmissible agents and provide an added safeguard against newly emerging infectious threats of most types. Current pathogen reduction methods also inactivate leukocytes, adding safety benefits similar to leukocyte removal and product irradiation. However, to date, concerns about the safety and efficacy of cellular blood components treated by pathogen reduction have prevented approval of these technologies in the U.S. and Canada. FDA is promoting clinical and basic scientific studies to clarify these issues and would consider alternative approaches to assuring blood safety if pathogen reduction technologies are proven to be safe and effective.     

Quality control issues in point of care testing

* Quality Control (QC) in Point of Care Testing (PoCT) is often thought of as a complex issue; however intelligent system analysis can simplify matters and greatly increase the chances of a well controlled system. What we want to achieve is a QC program which adequately controls the PoCT system, but does not excessively contribute to the operating costs or complexity of maintaining a PoCT instrument, or network of instruments. * Don't neglect effective pre-analytical work: good documentation, operator training, monitoring, and analyser maintenance programs are essential, as for any analyser. * Look closely at your analyser: Is it a "laboratory type" instrument or cartridge or strip based? Can it perform multiple test types or a single test only? How is it calibrated? Does it have built in self-check capabilities or an electronic check cartridge? Is the sample in contact with the instrument? What are the cartridge/strip/reagent storage requirements? * Establish where the analysis is taking place and which system component is involved. * Tailor your QC program to target this component, but still check the system as a whole. * A common approach is to check cartridges/strips on delivery and run a QA sample at least monthly to check storage conditions and operator performance. If there is no independent electronic instrument check, daily QC checks are also recommended. * Don't be afraid to stray beyond conventional QC models if necessary. Some PoCT systems are not adequately controlled by the application of conventional QC alone.     

Biosensors in process control

Improvement in bioprocess control will require development of monitors for a wide range of cell-growth and downstream-process parameters. These requirements are examined in terms of the development and application of biosensor devices and physical measurement techniques. Acoustic, dielectric and laser light scattering techniques are discussed primarily as monitors and analysers for biomass parameters. Developments with biosensor devices are discussed in terms of their application in membrane sampling-flow analysis probes and the potential of more direct biosensing principles.     

Evaluating online direct-to-consumer marketing of genetic tests: informed choices or buyers beware?

Commercialization of genetic technologies is expanding the horizons for the marketing and sales of genetic tests direct-to-consumers (DTCs). This study assesses the information provision and access requirements that are in place for genetic tests that are being advertised DTC over the Internet. Sets of key words specific to DTC genetic testing were entered into popular Internet search engines to generate a list of 24 companies engaging in DTC advertising. Company requirements for physician mediation, genetic counseling arrangements, and information provision were coded to develop categories for quantitative analysis within each variable. Results showed that companies offering risk assessment and diagnostic testing were most likely to require that testing be mediated by a clinician, and to recommend physician-arranged counseling. Companies offering enhancement testing were less likely to require physician mediation of services and more likely to provide long-distance genetic counseling. DTC advertisements often provided information on disease etiology; this was most common in the case of multifactorial diseases. The majority of companies cited outside sources to support the validity of claims about clinical utility of the tests being advertised; companies offering risk assessment tests most frequently cited all information sources. DTC advertising for genetic tests that lack independent professional oversight raises troubling questions about appropriate use and interpretation of these tests by consumers and carries implications for the standards of patient care. These implications are discussed in the context of a public healthcare system.     

Bioluminescent kinase strips: A novel approach to targeted and flexible kinase inhibitor profiling

In addition to target efficacy, drug safety is a major requirement during the drug discovery process and is influenced by target specificity. Therefore, it is imperative that every new drug candidate be profiled against various liability panels that include protein kinases. Here, an effective methodology to streamline kinase inhibitor profiling is described. An accessible standardized profiling system for 112 protein kinases covering all branches of the kinome was developed. This approach consists of creating different sets of kinases and their corresponding substrates in multi-tube strips. The kinase stocks are pre-standardized for optimal kinase activity and used for inhibitor profiling using a bioluminescent ADP detection assay. We show that these strips can routinely generate inhibitor selectivity profiles for small or broad kinase family panels. Lipid kinases were also assembled in strip format and profiled together with protein kinases. We identified two specific PI3K inhibitors that have off-target effects on CK2 that were not reported before and would have been missed if compounds were not profiled against lipid and protein kinases simultaneously. To validate the accuracy of the data generated by this method, we confirmed that the inhibition potencies observed are consistent with published values produced by more complex technologies such as radioactivity assays.     

Costal Strip Accumulation and Lorica Assembly In the Marine Choanoflagellate Diplotheca Costata Valkanov

ABSTRACT The lorica of the tectiform choanoflagellate D. costata contains five categories of costal strips distinguishable from each other on the basis of morphology and patterning. Categories of strips include those forming the anterior transverse costa; the anterior, intermediate, and posterior costal strips, respectively, of the longitudinal costae and those constituting the posterior transverse costa. the distinctive morphology of each class of strips makes it possible to observe their location and orientation within the overall accumulation of strips at the top of the parent cell collar. In Diplotheca costata the orientation and positioning of the different categories of strips in an accumulation anticipates their orientation and imbrication in the mature lorica. Assembly of the lorica from an accumulation of strips involves lateral sliding of costal strips to constitute transverse costae and longitudinal sliding of strips to constitute longitudinal costae. the motive force for lorica assembly is provided by extension of the anterolateral tentacles.     

Small-scale systems for in vivo drug delivery

Recent developments in the application of micro- and nanosystems for drug administration include a diverse range of new materials and methods. New approaches include the on-demand activation of molecular interactions, novel diffusion-controlled delivery devices, nanostructured 'smart' surfaces and materials, and prospects for coupling drug delivery to sensors and implants. Micro- and nanotechnologies are enabling the design of novel methods such as radio-frequency addressing of individual molecules or the suppression of immune response to a release device. Current challenges include the need to balance the small scale of the devices with the quantities of drugs that are clinically necessary, the requirement for more stable sensor platforms, and the development of methods to evaluate these new materials and devices for safety and efficacy.     

Technical mitigation to reduce marine mammal bycatch and entanglement in commercial fishing gear: lessons learnt and future directions

Fisheries bycatch is one of the biggest threats to marine mammal populations. A literature review was undertaken to provide a comprehensive assessment and synopsis of gear modifications and technical devices to reduce marine mammal bycatch in commercial trawl, purse seine, longline, gillnet and pot/trap fisheries. Successfully implemented mitigation measures include acoustic deterrent devices (pingers) which reduced the bycatch of some small cetacean species in gillnets, appropriately designed exclusion devices which reduced pinniped bycatch in some trawl fisheries, and various pot/trap guard designs that reduced marine mammal entrapment. However, substantial development and research of mitigation options is required to address the bycatch of a range of species in many fisheries. No reliably effective technical solutions to reduce small cetacean bycatch in trawl nets are available, although loud pingers have shown potential. There are currently no technical options that effectively reduce marine mammal interactions in longline fisheries, although development of catch and hook protection devices is promising. Solutions are also needed for species, particularly pinnipeds and small cetaceans, that are not deterred by pingers and continue to be caught in static gillnets. Large whale entanglements in static gear, particularly buoy lines for pots/traps, needs urgent attention although there is encouraging research on rope-less pot/trap systems and identification of rope colours that are more detectable to whale species. Future mitigation development and deployment requires rigorous scientific testing to determine if significant bycatch reduction has been achieved, as well as consideration of potentially conflicting mitigation outcomes if multiple species are impacted by a fishery.

     

Pecking preferences and pre-dispositions in domestic chicks: implications for the development of environmental enrichment devices

Environmental enrichment is thought likely to benefit chickens and farmers in many ways; these include reduced fearfulness and feather pecking and improved productivity. Enrichment devices would intuitively be more effective if they reliably attracted and sustained appreciable interest but many fail to do so. This may reflect the fact that the choice of stimuli often reflects availability and human preconceptions rather than a critical consideration of the birds' preferences and pre-dispositions. We had previously identified string as a particularly attractive pecking stimulus for chicks and adult hens (Gallus gallus domesticus) of a laying strain (ISA Brown). In the present study we found that chicks of another laying strain (Lohmann Brown) also pecked sooner and more at a bunch of string than at chains or beads (Experiment 1). White or yellow strings were preferred to red, green or blue ones (Experiment 2) and white string elicited more pecking than did combinations of white and yellow or of all five colours (Experiment 3). Varying the length and width of the bunches of string exerted no detectable effects on pecking (Experiment 4) whereas incorporating small, shiny beads in the white string devices actually reduced pecking (Experiment 5). Virtually all the devices elicited progressively more interest with repeated presentation; this trend was particularly marked for white string. Collectively, the present findings demonstrate that young domestic chicks have clear and specific pecking preferences. Although the magnitude of response varied across experiments, white string consistently elicited the most interest. Our two main conclusions are: (i) white or yellow strings were particularly attractive stimuli that drew increasing interest, at least in the short term, and (ii) simple devices were preferred to more complex ones, or at least to those used here.     

Coverage of genetic technologies under national health reform.

This article examines the extent to which the technologies expected to emerge from genetic research are likely to be covered under Government-mandated health insurance programs such as those being proposed by advocates of national health reform. Genetic technologies are divided into three broad categories; genetic information services, including screening, testing, and counseling; experimental technologies; and gene therapy. This article concludes that coverage of these technologies under national health reform is uncertain. The basic benefits packages provided for in the major health reform plans are likely to provide partial coverage of experimental technologies; relatively broad coverage of information services; and varying coverage of gene therapies, on the basis of an evaluation of their costs, benefits, and the degree to which they raise objections on political and religious grounds. Genetic services that are not included in the basic benefits package will be available only to those who can purchase supplemental insurance or to those who can purchase the services with personal funds. The resulting multitiered system of access to genetic services raises serious questions of fairness.     

综述与专论: 基于核酸适配体传感器的即时检测（POCT）技术

即时检测（point-of-care testing，POCT）是一种检测成本低、检测速度快、准确度高、能自我采样获得临床诊断结果的新型诊断技术。该技术在临床诊断、病情监控与疫情防控等领域发挥了重要作用。核酸适配体是一种能够特异性识别多种靶标的分子探针，具有易合成、批间差异小、易实现信号放大等突出优势，是生物医学传感器中重要的分子识别元件。本文概述了核酸适配体探针的现有筛选方法和进展，总结了核酸适配体POCT传感器信号放大策略，着重介绍了各类核酸适配体传感器在POCT领域的应用现状，并对核酸适配体POCT传感器的发展前景进行了展望。     

The elastic properties of canine abdominal aorta at its branches

The elastic properties of the abdominal aorta at regions of junctions were studied using strips from 17 dogs. Strips of tissue cut longitudinally and circumferentially at the celiac, mesenteric, and renal branches were used to compare the properties of the proximal and distal junctions, as well as the aorta and artery regions adjoining. The tissues were stored for at least 24 h to ensure that no active component of the smooth muscle remained. The elastic properties measured here are due to elastin and collagen, with a small contribution from dead smooth muscle cells. The tissue strips were tested at 20 degrees C while immersed in saline using an Instron tensile testing machine. Elongation of the three regions was measured from photographs taken as the tissue was stretched. Stress values went to 200 kN/m2 as the strain increased to approximately 0.8. (The physiological range for the dog was calculated as 40-85 kN/m2.) The distal junctional region was found to be the most extensible for both longitudinally and circumferentially oriented strips. These results have important implications for flow models as they imply that the shape of the junctional region probably changes between diastole and systole.