Nam K. Tran

Multiplex polymerase chain reaction detection enhancement of bacteremia and fungemia.

Objective:To test a multiplex real-time polymerase chain reaction (PCR) method for simultaneous detection of multiple organisms in bloodstream infections. Methods:Prospective observational study at the University of California Davis Medical Center (Sacramento, CA). Two hundred adult (>18 yrs) patients from the emergency room, intensive care units, and general medicine wards at risk of a bloodstream infection and who manifested signs of systemic inflammatory response syndrome (SIRS). Whole blood samples for PCR testing were collected at the same time as blood culture (BC). PCR results were compared to blood and other culture results. Results:PCR detected potentially significant bacteria and fungi in 45 cases compared to 37 by BC. PCR detected the methicillin resistance (mecA) gene in all three culture-confirmed methicillin-resistant Staphylococcus aureus cases. More than 68% of PCR results were confirmed by blood, urine, and catheter culture. Independent clinical arbitrators could not rule out the potential clinical significance of organism(s) detected by PCR, but not by BC. PCR did not detect Enterococcus faecalis in five BC-confirmed cases. On average, seven patient samples could be tested simultaneously with the PCR method in 6.54 ± .27 hrs. Conclusions:Multiplex PCR detected potentially significant bacteria and fungi that were not found by BC. BC found organisms that were not detected by PCR. Despite limitations of both BC and PCR methods, PCR could serve as an adjunct to current culture methods to facilitate early detection of bloodstream infections. Early detection of microorganisms has the potential to facilitate evidence-based treatment decisions, antimicrobial selection, and adequacy of antimicrobial therapy.

Thermal stress and point-of-care testing performance: suitability of glucose test strips and blood gas cartridges for disaster response.

OBJECTIVE Point-of-care testing (POCT) devices are deployed in the field for emergency on-site testing under a wide range of environmental conditions. Our objective was to evaluate the performance of glucose meter test strips and handheld blood gas analyzer cartridges following thermal stresses that simulate field conditions. METHODS We evaluated electrochemical and spectrophotometric glucose meter systems and a handheld blood gas analyzer. Glucose test strips were cold-stressed (-21 degrees C) and heat-stressed (40 degrees C) for up to 4 weeks. Blood gas cartridges were stressed at -21 degrees C, 2 degrees C, and 40 degrees C for up to 72 hours. Test strip and cartridge performance was evaluated using aqueous quality control solutions. Results were compared with those obtained with unstressed POCT strips and cartridges. RESULTS Heated glucose test strips and blood gas cartridges yielded elevated results. Frozen test strips and cooled cartridges yielded depressed glucose and blood gas results, respectively. Frozen cartridges failed. CONCLUSIONS The performance of glucose test strips and blood gas cartridges was affected adversely by thermal stresses. Heating generated elevated results, and cooling depressed results. Disaster medical assistance teams and emergency medical responders should be aware of these risks. Field POCT devices must be robust to withstand adverse conditions. We recommend that industry produce POCT devices and reagents suitable for disaster medical assistance teams.

Assessing the Performance of Handheld Glucose Testing for Critical Care

BACKGROUND We assessed the performance of a point-of-care (POC) glucose meter system (GMS) with multitasking test strip by using the locally-smoothed (LS) median absolute difference (MAD) curve method in conjunction with a modified Bland-Altman difference plot and superimposed International Organization for Standardization (ISO) 15197 tolerance bands. We analyzed performance for tight glycemic control (TGC). METHODS A modified glucose oxidase enzyme with a multilayer-gold, multielectrode, four-well test strip (StatStriptrade mark, NOVA Biomedical, Waltham, MA) was used. There was no test strip calibration code. Pragmatic comparison was done of GMS results versus paired plasma glucose measurements from chemistry analyzers in clinical laboratories. Venous samples (n = 1,703) were analyzed at 35 hospitals that used 20 types of chemistry analyzers. Erroneous results were identified using the Bland-Altman plot and ISO 15197 criteria. Discrepant values were analyzed for the TGC interval of 80-110 mg/dL. RESULTS The GMS met ISO 15197 guidelines; 98.6% (410 of 416) of observations were within tolerance for glucose <75 mg/dL, and for > or =75 mg/dL, 100% were within tolerance. Paired differences (handheld minus reference) averaged -2.2 (SD 9.8) mg/dL; the median was -1 (range, -96 to 45) mg/dL. LS MAD curve analysis revealed satisfactory performance below 186 mg/dL; above 186 mg/dL, the recommended error tolerance limit (5 mg/dL) was not met. No discrepant values appeared. All points fell in Clarke Error Grid zone A. Linear regression showed y = 1.018x - 0.716 mg/dL, and r2 = 0.995. CONCLUSIONS LS MAD curves draw on human ability to discriminate performance visually. LS MAD curve and ISO 15197 performance were acceptable for TGC. POC and reference glucose calibration should be harmonized and standardized.

Worldwide Point-of-care Testing: Compendiums of Poct for Mobile, Emergency, Critical, and Primary Care and of Infectious Diseases Tests

Abstract:We present two compendiums of point-of-care devices and rapid response tests available worldwide. Information was gathered from both direct and indirect survey sources and crystallized into two tables, one a summary of POCT for mobile, emergency, critical, and primary care, and the other, a

CONTINUOUS NONINVASIVE HEMOGLOBIN MONITORING: THE STANDARD OF CARE AND FUTURE IMPACT

While the authors present analysis of trends, observations reflect more static, than dynamic hematological conditions, and they suggest that CNHM “…may be a feasible alternative to invasive hemoglobin monitoring”. However, they do not present decision-making or outcomes results, per se, and wisely, stop short of implying CNHM should replace discrete in vitro diagnostic hemoglobin testing when the article ends with the somewhat circuitous caveat, “A laboratory hemoglobin determination could be limited to situations where a blood transfusion is considered”. Oxygen saturation measured noninvasively by traditional pulse oximetry using red (~660 nm) and infrared (~905 nm) light emitting diodes (LEDs) differentiates oxy- versus deoxyhemoglobin, respectively (2). The ratio of red versus infrared light is correlated with a calibration curve empirically derived from clinical studies to calculate oxygen saturation over a limited range (2, 3), while pulse rate is determined from the plethysmogram. Newer devices incorporate robust treatment of the red/infrared ratio, multiple wavelengths, advanced algorithms, and proprietary sensor calibrations integrated (3). These principles extend to pulse co-oximetry, where up to twelve wavelengths and sophisticated signal reduction enable measurement of carboxyhemoglobin, methemoglobin, total hemoglobin,

Point-of-care testing for disasters: needs assessment, strategic planning, and future design.

Objective evidence-based national surveys serve as a first step in identifying suitable point-of-care device designs, effective test clusters, and environmental operating conditions. Preliminary survey results show the need for point-of-care testing (POCT) devices using test clusters that specifically detect pathogens found in disaster scenarios. Hurricane Katrina, the tsunami in southeast Asia, and the current influenza pandemic (H1N1, “swine flu”) vividly illustrate lack of national and global preparedness. Gap analysis of current POCT devices versus survey results reveals how POCT needs can be fulfilled. Future thinking will help avoid the worst consequences of disasters on the horizon, such as extensively drug-resistant tuberculosis and pandemic influenzas. A global effort must be made to improve POC technologies to rapidly diagnose and treat patients to improve triaging, on-site decision making, and, ultimately, economic and medical outcomes.

Bedside Glucose Monitoring—is it Safe? A New, Regulatory-compliant Risk Assessment Evaluation Protocol in Critically Ill Patient Care Settings*

Objectives: New data have emerged from ambulatory and acute care settings about adverse patient events, including death, attributable to erroneous blood glucose meter measurements and leading to questions over their use in critically ill patients. The U.S. Food and Drug Administration published new, more stringent guidelines for glucose meter manufacturers to evaluate the performance of blood glucose meters in critically ill patient settings. The primary objective of this international, multicenter, multidisciplinary clinical study was to develop and apply a rigorous clinical accuracy assessment algorithm, using four distinct statistical tools, to evaluate the clinical accuracy of a blood glucose monitoring system in critically ill patients. Design: Observational study. Setting: Five international medical and surgical ICUs. Patients: All patients admitted to critical care settings in the centers. Interventions: None. Measurements and Main Results: Glucose measurements were performed on 1,698 critically ill patients with 257 different clinical conditions and complex treatment regimens. The clinical accuracy assessment algorithm comprised four statistical tools to assess the performance of the study blood glucose monitoring system compared with laboratory reference methods traceable to a definitive standard. Based on POCT12-A3, the Clinical Laboratory Standards Institute standard for hospitals about hospital glucose meter procedures and performance, and Parkes error grid clinical accuracy performance criteria, no clinically significant differences were observed due to patient condition or therapy, with 96.1% and 99.3% glucose results meeting the respective criteria. Stratified sensitivity and specificity analysis (10 mg/dL glucose intervals, 50–150 mg/dL) demonstrated high sensitivity (mean = 95.2%, SD = ± 0.02) and specificity (mean = 95. 8%, SD = ± 0.03). Monte Carlo simulation modeling of the study blood glucose monitoring system showed low probability of category 2 and category 3 insulin dosing error, category 2 = 2.3% (41/1,815) and category 3 = 1.8% (32/1,815), respectively. Patient trend analysis demonstrated 99.1% (223/225) concordance in characterizing hypoglycemic patients. Conclusions: The multicomponent, clinical accuracy assessment algorithm demonstrated that the blood glucose monitoring system was acceptable for use in critically ill patient settings when compared to the central laboratory reference method. This clinical accuracy assessment algorithm is an effective tool for comprehensively assessing the validity of whole blood glucose measurement in critically ill patient care settings.

Mapping point-of-care performance using locally-smoothed median and maximum absolute difference curves.

Abstract Background: The goal is to introduce visual performance mapping efficient for establishing acceptance criteria and facilitating decisions regarding the utility of hospital point-of-care devices. This approach uniquely reveals the quality of performance locally, as opposed to globally. Methods: After presenting theoretical foundations, this study illustrates the approach by applying it to six hospital glucose meter systems (GMSs) using clinical multi-center (n=2767) and multi-system (n=613, n=100) observations. Results: LS MAD curves identified breakouts, that is, points where the locally-smoothed median absolute difference (LS MAD) curve exceeds the recommended error tolerance limit of 5 mg/dL (0.28 mmol/L). LS maximum absolute difference (MaxAD) breakthroughs, which occur where the LS MaxAD curve exceeds the 99th percentile of MaxADs from x=30–200 mg/dL (1.67–11.10 mmol/L), showed extreme error locations. A multi-sensor interference- and hematocrirt-correcting GMS displayed a flat LS MAD curve until it reached a breakout of 179 mg/dL (9.94 mmol/L) and generated breakthroughs that could affect bedside decision-making, but less erratically than other systems with inadequate performance for hospital critical care. We discovered Class I (meter high, reference low) and Class II (converse) discrepant values in some systems. Class I errors could lead to inappropriate insulin dosing and hypoglycemic episodes in tight glucose control. Conclusions: LS MAD-MaxAD curves help assess the performance of point-of-care testing. Visual mapping of systematic and random errors locally over the entire analyte measurement range in a single integrated display is an advantage when considering the adverse impact of zones of poor quantitative performance on specific clinical applications, threshold-driven bedside decisions and the care of critically ill patients.

Design of a cost-effective, hemodynamically adjustable model for resuscitative endovascular balloon occlusion of the aorta (REBOA) simulation

ABSTRACT Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct technique for salvaging patients with noncompressible torso hemorrhage. Current REBOA training paradigms require large animals, virtual reality simulators, or human cadavers for acquisition of skills. These training strategies are expensive and resource intensive, which may prevent widespread dissemination of REBOA. We have developed a low-cost, near-physiologic, pulsatile REBOA simulator by connecting an anatomic vascular circuit constructed out of latex and polyvinyl chloride tubing to a commercially available pump. This pulsatile simulator is capable of generating cardiac outputs ranging from 1.7 to 6.8 L/min with corresponding arterial blood pressures of 54 to 226/14 to 121 mmHg. The simulator accommodates a 12 French introducer sheath and a CODA balloon catheter. Upon balloon inflation, the arterial waveform distal to the occlusion flattens, distal pulsation within the simulator is lost, and systolic blood pressures proximal to the balloon catheter increase by up to 62 mmHg. Further development and validation of this simulator will allow for refinement, reduction, and replacement of large animal models, costly virtual reality simulators, and perfused cadavers for training purposes. This will ultimately facilitate the low-cost, high-fidelity REBOA simulation needed for the widespread dissemination of this life-saving technique.

Point-of-care B-type natriuretic peptide and neutrophil gelatinase-associated lipocalin measurements for acute resuscitation: a pilot study.

Adequate resuscitation is paramount to burn patient survival and recovery. Novel biomarkers of intravascular volume and renal perfusion may augment resuscitation strategies. The purpose of this study is to characterize serum B-type natriuretic peptide (BNP) and neutrophil gelatinase-associated lipocalin (NGAL) during burn resuscitation and correlate to clinical assessments of volume status. We hypothesize that BNP and NGAL will help predict inadequate resuscitation during the first 48 hours following burn injury. We conducted a pilot observational study recruiting 15 adult (age ≥18 years) patients with ≥20% TBSA burns. Paired serial BNP, NGAL, and creatinine measurements were performed using point-of-care testing. Samples were tested every 4 hours for the first 48 hours following admission. Acute kidney injury (AKI) was defined by the RIFLE criteria. Over-resuscitation was defined as developing compartment syndrome. Demographics and TBSA were similar between AKI (n = 7) vs non-AKI (n = 8), and over-resuscitated (n = 5) vs adequately resuscitated groups (n = 10). NGAL (184.9 ± 72.2 vs 110.8 ± 35.8 ng/ml, P = .004) and BNP (25.3 ± 17.3 vs 8.8 ± 5.2 pg/ml, P = .033) values were significantly higher in AKI patients. Creatinine values were similar between AKI and non-AKI patients. NGAL levels suggested presence of AKI 12 hours earlier than creatinine levels. BNP values (23.1 ± 21.9 vs 13.9 ± 13.4 pg/ml, P < .001) were significantly higher in over-resuscitated patients. Point-of-care BNP, NGAL, and creatinine measurements aid in the assessment of vascular volume and renal function during acute burn resuscitation. Further studies are warranted to determine BNP and NGAL cut-offs for guiding burn resuscitation.