Is perioperative point-of-care prothrombin time testing accurate compared to the standard laboratory test?

There is no accepted way of measuring prothrombin time without time loss for patients undergoing major surgery who are at risk of intraoperative dilution and consumption coagulopathy due to bleeding and volume replacement with crystalloids or colloids. Decisions to transfuse fresh frozen plasma and procoagulatory drugs have to rely on clinical judgment in these situations. Point-of-care devices are considerably faster than the standard laboratory methods. In this study we assessed the accuracy of a Point-of-care (PoC) device measuring prothrombin time compared to the standard laboratory method. Patients undergoing major surgery and intensive care unit patients were included. PoC prothrombin time was measured by CoaguChek XS Plus (Roche Diagnostics, Switzerland). PoC and reference tests were performed independently and interpreted under blinded conditions. Using a cut-off prothrombin time of 50%, we calculated diagnostic accuracy measures, plotted a receiver operating characteristic (ROC) curve and tested for equivalence between the two methods. PoC sensitivity and specificity were 95% (95% CI 77%, 100%) and 95% (95% CI 91%, 98%) respectively. The negative likelihood ratio was 0.05 (95% CI 0.01, 0.32). The positive likelihood ratio was 19.57 (95% CI 10.62, 36.06). The area under the ROC curve was 0.988. Equivalence between the two methods was confirmed. CoaguChek XS Plus is a rapid and highly accurate test compared with the reference test. These findings suggest that PoC testing will be useful for monitoring intraoperative prothrombin time when coagulopathy is suspected. It could lead to a more rational use of expensive and limited blood bank resources.

Routine use of point-of-care tests: usefulness and application in clinical microbiology.

Point-of-care (POC) tests offer potentially substantial benefits for the management of infectious diseases, mainly by shortening the time to result and by making the test available at the bedside or at remote care centres. Commercial POC tests are already widely available for the diagnosis of bacterial and viral infections and for parasitic diseases, including malaria. Infectious diseases specialists and clinical microbiologists should be aware of the indications and limitations of each rapid test, so that they can use them appropriately and correctly interpret their results. The clinical applications and performance of the most relevant and commonly used POC tests are reviewed. Some of these tests exhibit insufficient sensitivity, and should therefore be coupled to confirmatory tests when the results are negative (e.g. Streptococcus pyogenes rapid antigen detection test), whereas the results of others need to be confirmed when positive (e.g. malaria). New molecular-based tests exhibit better sensitivity and specificity than former immunochromatographic assays (e.g. Streptococcus agalactiae detection). In the coming years, further evolution of POC tests may lead to new diagnostic approaches, such as panel testing, targeting not just a single pathogen, but all possible agents suspected in a specific clinical setting. To reach this goal, the development of serology-based and/or molecular-based microarrays/multiplexed tests will be needed. The availability of modern technology and new microfluidic devices will provide clinical microbiologists with the opportunity to be back at the bedside, proposing a large variety of POC tests that will allow quicker diagnosis and improved patient care.

Evaluation of different POCT devices for glucose measurement in a clinical neonatal setting.

Hypoglycaemia is a major cause of neonatal morbidity and may induce long-term developmental sequelae. Clinical signs of hypoglycaemia in neonatal infants are unspecific or even absent, and therefore, precise and accurate methods for the assessment of glycaemia are needed. Glycaemia measurement in newborns has some particularities like a very low limit of normal glucose concentration compared to adults and a large range of normal haematocrit values. Many bedside point-of-care testing (POCT) systems are available, but literature about their accuracy in newborn infants is scarce and not very convincing. In this retrospective study, we identified over a 1-year study period 1,324 paired glycaemia results, one obtained at bedside with one of three different POCT systems (Elite? XL, Ascensia? Contour? and ABL 735) and the other in the central laboratory of the hospital with the hexokinase reference method. All three POCT systems tended to overestimate glycaemia values, and none of them fulfilled the ISO 15197 accuracy criteria. The Elite XL appeared to be more appropriate than Contour to detect hypoglycaemia, however with a low specificity. Contour additionally showed an important inaccuracy with increasing haematocrit. The bench analyzer ABL 735 was the most accurate of the three tested POCT systems. Both of the tested handheld glucometers have important drawbacks in their use as screening tools for hypoglycaemia in newborn infants. ABL 735 could be a valuable alternative, but the blood volume needed is more than 15 times higher than for handheld glucometers. Before daily use in the newborn population, careful clinical evaluation of each new POCT system for glucose measurement is of utmost importance.

Does Radar Technology Support the Diagnosis of Pneumothorax? PneumoScan-A Diagnostic Point-of-Care Tool

Background. A nonrecognized pneumothorax (PTX) may become a life-threatening tension PTX. A reliable point-of-care diagnostic tool could help in reduce this risk. For this purpose, we investigated the feasibility of the use of the PneumoScan, an innovative device based on micropower impulse radar (MIR). Patients and Methods. addition to a standard diagnostic protocol including clinical examination, chest X-ray (CXR), and computed tomography (CT), 24 consecutive patients with chest trauma underwent PneumoScan testing in the shock trauma room to exclude a PTX. Results. The application of the PneumoScan was simple, quick, and reliable without functional disorder. Clinical examination and CXR each revealed one and PneumoScan three out of altogether four PTXs (sensitivity 75%, specificity 100%, positive predictive value 100%, and negative predictive value 95%). The undetected PTX did not require intervention. Conclusion. The PneumoScan as a point-of-care device offers additional diagnostic value in patient management following chest trauma. Further studies with more patients have to be performed to evaluate the diagnostic accuracy of the device.

Developing a point-of-care electronic medical record system for TB/HIV co-infected patients: experiences from Lighthouse Trust, Lilongwe, Malawi.

BACKGROUND Implementation of user-friendly, real-time, electronic medical records for patient management may lead to improved adherence to clinical guidelines and improved quality of patient care. We detail the systematic, iterative process that implementation partners, Lighthouse clinic and Baobab Health Trust, employed to develop and implement a point-of-care electronic medical records system in an integrated, public clinic in Malawi that serves HIV-infected and tuberculosis (TB) patients. METHODS Baobab Health Trust, the system developers, conducted a series of technical and clinical meetings with Lighthouse and Ministry of Health to determine specifications. Multiple pre-testing sessions assessed patient flow, question clarity, information sequencing, and verified compliance to national guidelines. Final components of the TB/HIV electronic medical records system include: patient demographics; anthropometric measurements; laboratory samples and results; HIV testing; WHO clinical staging; TB diagnosis; family planning; clinical review; and drug dispensing. RESULTS Our experience suggests that an electronic medical records system can improve patient management, enhance integration of TB/HIV services, and improve provider decision-making. However, despite sufficient funding and motivation, several challenges delayed system launch including: expansion of system components to include of HIV testing and counseling services; changes in the national antiretroviral treatment guidelines that required system revision; and low confidence to use the system among new healthcare workers. To ensure a more robust and agile system that met all stakeholder and user needs, our electronic medical records launch was delayed more than a year. Open communication with stakeholders, careful consideration of ongoing provider input, and a well-functioning, backup, paper-based TB registry helped ensure successful implementation and sustainability of the system. Additional, on-site, technical support provided reassurance and swift problem-solving during the extended launch period. CONCLUSION Even when system users are closely involved in the design and development of an electronic medical record system, it is critical to allow sufficient time for software development, solicitation of detailed feedback from both users and stakeholders, and iterative system revisions to successfully transition from paper to point-of-care electronic medical records. For those in low-resource settings, electronic medical records for integrated care is a possible and positive innovation.

Assessment of Two Diabetes Point-of-Care Analyzers Measuring Hemoglobin A1c in the Peruvian Amazon

Aims: Measurement of glycated hemoglobin (HbA1c) is an important indicator of glucose control over time. Point-of-care (POC) devices allow for rapid and convenient measurement of HbA1c, greatly facilitating diabetes care. We assessed two POC analyzers in the Peruvian Amazon where laboratory-based HbA1c testing is not available.

Methods: Venous blood samples were collected from 203 individuals from six different Amazonian communities with a wide range of HbA1c, 4.4-9.0% (25-75 mmol/mol). The results of the Afinion AS100 and the DCA Vantage POC analyzers were compared to a central laboratory using the Premier Hb9210 high-performance liquid chromatography (HPLC) method. Imprecision was assessed by performing 14 successive tests of a single blood sample.

Results: The correlation coefficient r for POC and HPLC results was 0.92 for the Afinion and 0.93 for the DCA Vantage. The Afinion generated higher HbA1c results than the HPLC (mean difference = +0.56% [+6 mmol/mol]; p < 0.001), as did the DCA Vantage (mean difference = +0.32% [4 mmol/mol]). The bias observed between POC and HPLC did not vary by HbA1c level for the DCA Vantage (p = 0.190), but it did for the Afinion (p < 0.001). Imprecision results were: CV = 1.75% for the Afinion, CV = 4.01% for the DCA Vantage. Sensitivity was 100% for both devices, specificity was 48.3% for the Afinion and 85.1% for the DCA Vantage, positive predictive value (PPV) was 14.4% for the Afinion and 34.9% for the DCA Vantage, and negative predictive value (NPV) for both devices was 100%. The area under the receiver operating characteristic (ROC) curve was 0.966 for the Afinion and 0.982 for the DCA Vantage. Agreement between HPLC and POC in classifying diabetes and prediabetes status was slight for the Afinion (Kappa = 0.12) and significantly different (McNemar’s statistic = 89; p < 0.001), and moderate for the DCA Vantage (Kappa = 0.45) and significantly different (McNemar’s statistic = 28; p < 0.001).

Conclusions: Despite significant variation of HbA1c results between the Afinion and DCA Vantage analyzers compared to HPLC, we conclude that both analyzers should be considered in health clinics in the Peruvian Amazon for therapeutic adjustments if healthcare workers are aware of the differences relative to testing in a clinical laboratory. However, imprecision and bias were not low enough to recommend either device for screening purposes, and the local prevalence of anemia and malaria may interfere with diagnostic determinations for a substantial portion of the population.

Linearity analysis and comparison study on the epoc® point-of-care blood analysis system in cardiopulmonary bypass patients

The epoc® blood analysis system (Epocal Inc., Ottawa, Ontario, Canada) is a newly developed in vitro diagnostic hand-held analyzer for testing whole blood samples at point-of-care, which provides blood gas, electrolytes, ionized calcium, glucose, lactate, and hematocrit/calculated hemoglobin rapidly. The analytical performance of the epoc® system was evaluated in a tertiary hospital, see related research article “Analytical evaluation of the epoc® point-of-care blood analysis system in cardiopulmonary bypass patients” [1]. Data presented are the linearity analysis for 9 parameters and the comparison study in 40 cardiopulmonary bypass patients on 3 epoc® meters, Instrumentation Laboratory GEM4000, Abbott iSTAT, Nova CCX, and Roche Accu-Chek Inform II and Performa glucose meters.

A biomimetic sensor for monitoring oxidative stress biomarker in point-of-care

1st ASPIC International Congress

Protein-responsive polymers for point-of-care detection of cardiac biomarker

This work describes a novel use for the polymeric film, poly(o-aminophenol) (PAP) that was made responsive to a specific protein. This was achieved through templated electropolymerization of aminophenol (AP) in the presence of protein. The procedure involved adsorbing protein on the electrode surface and thereafter electroploymerizing the aminophenol. Proteins embedded at the outer surface of the polymeric film were digested by proteinase K and then washed away thereby creating vacant sites. The capacity of the template film to specifically rebind protein was tested with myoglobin (Myo), a cardiac biomarker for ischemia. The films acted as biomimetic artificial antibodies and were produced on a gold (Au) screen printed electrode (SPE), as a step towards disposable sensors to enable point-of-care applications. Raman spectroscopy was used to follow the surface modification of the Au-SPE. The ability of the material to rebind Myo was measured by electrochemical techniques, namely electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SWV). The devices displayed linear responses to Myo in EIS and SWV assays down to 4.0 and 3.5 μg/mL, respectively, with detection limits of 1.5 and 0.8 μg/mL. Good selectivity was observed in the presence of troponin T (TnT) and creatine kinase (CKMB) in SWV assays, and accurate results were obtained in applications to spiked serum. The sensor described in this work is a potential tool for screening Myo in point-of-care due to the simplicity of fabrication, disposability, short time response, low cost, good sensitivity and selectivity.

Novel biosensing device for point-of-care applications with plastic antibodies grown on Au-Screen Printed Electrodes

A gold screen printed electrode (Au-SPE) was modified by merging Molecular Imprinting and Self-Assembly Monolayer techniques for fast screening cardiac biomarkers in point-of-care (POC). For this purpose, Myoglobin (Myo) was selected as target analyte and its plastic antibody imprinted over a glutaraldehyde (Glu)/cysteamine (Cys) layer on the gold-surface. The imprinting effect was produced by growing a reticulated polymer of acrylamide (AAM) and N,N′-methylenebisacrylamide (NNMBA) around the Myo template, covalently attached to the biosensing surface. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) studies were carried out in all chemical modification steps to confirm the surface changes in the Au-SPE. The analytical features of the resulting biosensor were studied by different electrochemical techniques, including EIS, square wave voltammetry (SWV) and potentiometry. The limits of detection ranged from 0.13 to 8 μg/mL. Only potentiometry assays showed limits of detection including the cut-off Myo levels. Quantitative information was also produced for Myo concentrations ≥0.2 μg/mL. The linear response of the biosensing device showed an anionic slope of ~70 mV per decade molar concentration up to 0.3 μg/mL. The interference of coexisting species was tested and good selectivity was observed. The biosensor was successfully applied to biological fluids.

Bioluminescent sensor proteins for point-of-care therapeutic drug monitoring.

For many drugs, finding the balance between efficacy and toxicity requires monitoring their concentrations in the patient's blood. Quantifying drug levels at the bedside or at home would have advantages in terms of therapeutic outcome and convenience, but current techniques require the setting of a diagnostic laboratory. We have developed semisynthetic bioluminescent sensors that permit precise measurements of drug concentrations in patient samples by spotting minimal volumes on paper and recording the signal using a simple point-and-shoot camera. Our sensors have a modular design consisting of a protein-based and a synthetic part and can be engineered to selectively recognize a wide range of drugs, including immunosuppressants, antiepileptics, anticancer agents and antiarrhythmics. This low-cost point-of-care method could make therapies safer, increase the convenience of doctors and patients and make therapeutic drug monitoring available in regions with poor infrastructure.

Biomarkkerit sepsiksen diagnostiikassa sekä Kvantitatiivisen prokalsitoniini-immunomäärityksen pystyttäminen ja optimointi point-of-care-ympäristöön

Termiä sepsis käytetään infektion aiheuttamasta yleisestä tulehdusreaktio-oireyhtymästä. Biokemiallinen merkkiaine eli biomarkkeri on aine, joka objektiivisesti mitattuna ja arvioituna toimii indikaattorina erottaen toisistaan normaalit biologiset prosessit ja patogeeniset prosessit. Lisäksi biomarkkeri saattaa osoittaa farmakologisen vasteen lääkehoidolle. Tutkielman kirjallisessa osassa on esitelty ja verrattu toisiinsa jo kliinisessä käytössä olevia sekä lupaavia, vielä tutkimusvaiheessa olevia, sepsiksen biomerkkiaineita. Lisäksi tutkielmassa on tarkasteltu sepsiksen todentamisen, tunnistamisen ja hoidon tulevaisuudennäkymiä. Prokalsitoniini (PCT) on eräs jo kliinisessä käytössä oleva sepsiksen biomerkkiaine. Tutkielman kokeellisessa osassa pystytettiin teho-osastoille suunnattu pikatesti PCT:n mittaamiseen aikaerotteista fluoresenssiteknologiaa hyödyntävälle AQT-järjestelmälle (DHR Finland Oy, Innotrac Diagnostics, Suomi). Järjestelmä mittaa 20–30 minuutissa biomerkkiainepitoisuuden. Tavoitteena oli löytää sopiva vasta-ainepari ja pystyttää kaksipuoleinen immunomääritys, jonka analyyttinen herkkyys on alle 0,02 ng/ml:ssa. Työssä tutkittiin biotinyloidun kokonaisen vasta-aineen ja paikkaspesifisesti biotinyloidun antigeenia sitovan fragmentin (engl. fragment antigen binding, Fab) toimivuutta sitojamolekyylinä. Lisäksi työssä verrattiin kahden eri leimamolekyylin, 9 hampaisen europiumkelaatin sekä Innotracissa kehitetyn tähtikelaatin, toimivuutta PCT-immunomäärityksessä. Vasta-aineiden mahdolliset ristireaktiot testattiin ja määritystä testattiin alustavasti eri näytematriiseissa. Työssä löydettiin 5 vasta-aineparia, joiden analyyttinen herkkyys oli alle 0,02 ng/ml:ssa. Aiemmin testattuja vasta-ainepareja parempi analyyttinen herkkyys johtui todennäköisesti yhden uuden leimavasta-aineen paremmasta affiniteetistä. Tähtikelaatilla leimatulla vasta-aineella analyyttinen herkkyys parani lähes viisinkertaisesti, kun sitä verrattiin 9-hampaisella euroopiumkelaatilla leimatun vasta-aineen määritykseen. Havaittiin myös, että Fab-fragmentilla mitattiin määrityksissä lähes kaksi kertaa suuremmat signaali-taustasuhteet, kun sitä verrattiin kokonaiseen vasta-aineeseen, tietyllä vasta-aineparilla. Tämä johtui luultavasti steeristen esteiden vähenemisestä. Näytematriisilla ei todettu olevan vaikutusta määritykseen, eikä ristireaktioita havaittu. Kehitetyn määrityksen suoriutumista verrattiin markkinoilla olevaan BRAHMS AG:n (Saksa) PCT-määritykseen käyttäen potilasnäytteitä. Korrelaatiokertoimet potilasnäytevertailuissa olivat 0,965–0,989 ja näytteiden mitatuissa pitoisuuksissa oli tasoero.