Deming Regression Research Articles

The accuracy of transcutaneous bilirubinometer measurements to identify the hyperbilirubinemia in outpatient newborn population

ObjectivesTo assess the ability of transcutaneous bilirubinometer for prediction total serum bilirubin levels in newborn infants after hospital discharge. MethodsNewborn infants requiring total serum bilirubin (TSB) level measurement during an outpatient follow-up visit were included into the study. Transcutaneous bilirubin (TcB) measurement was carried out using JH20-1C (Ningbo David, China) transcutaneous jaundice detector and total serum bilirubin was simultaneously determined by direct spectrophotometry. The agreement between paired TSB and TcB measurements were assessed by Bland-Altman plot and Deming regression analysis. Predictive indices were also identified in different TcB cut-off values for TSB levels of 222, 256 and 291 μmol/L. ResultsA total of 271 paired TcB and TSB measurements were obtained from 218 newborn infants. 40.2% had an age of above 7 days at measurement time. The mean difference (95% CI) between TcB and TSB values was −1.7 (−5.4 to 2.1) μmol/L. For TSB levels of at least 256 and 291 μmol/L, a TcB cut-off of 222 μmol/L shows sensitivity of 90.6% and 100%, respectively. It was also determined that 39.4% of TSB measurements could be avoided when using TcB cut-off value of 222 μmol/L. ConclusionThe measurement of TcB with JH20-1C seems to be a reliable screening method for hyperbilirubinemia in the outpatient population when used a TcB cut-off of 222 μmol/L. The use of transcutaneous bilirubinometer could reduce the number of invasive blood sampling for the determination serum bilirubin.

The commutability study of processed materials for serum alanine aminotransferase measurements

Objective To evaluate the commutability of 22 processed materials for serum alanine aminotransferase measurements which were performed in 11 routine assays without and 2 assays with pyridoxal-5′-phosphate. Methods 100 serum specimens were collected in Beijing Hospital, Zhao Yang Hospital and Tong Ren Hospital from May, 2017 to August, 2017. 50 individual specimens together with fresh frozen human serum pools (HSPs), external quality assessment (EQA) materials, commercial calibrators and controls were measured by 11 routine assays without pyridoxal-5′-phosphate. Measurement results of the 50 individual samples were pairwise analyzed by Deming regression for slopes and intercepts, and 95% prediction interval (PI) were calculated to evaluate the commutability of processed materials. Another 50 individual specimens and 22 above-mentioned materials were analyzed by 2 assays with pyridoxal-5′-phosphate as the evaluated methods and internationally recognized reference method as the comparative method. The ordinary linear regression (OLR) and 95% PI were used to identify the commutability of 22 materials. Results The Deming slopes ranged from 0.879 to 1.064 and intercepts from -1.96 to 3.30; the OLR slopes were 0.905 and 0.955 while intercepts were -6.71 and 9.53. The HSPs were commutable for 51/57 and 56/57 assay pairs. The EQA materials, commercial calibrators and controls showed noncommutability from 8/57 to 47/57, 38/57 and pairs after that, and from 13/57 to 43/57 assay pairs, respectively. Conclusion The lyophilized materials including EQA materials, commercial calibrators and controls demonstrated poor commutability in different degrees.(Chin J Lab Med, 2018, 41: 227-231) Key words: Alanine transaminase; Reference standards; Communication

Evaluation of linear regression techniques for atmospheric applications: the importance of appropriate weighting

Abstract. Linear regression techniques are widely used in atmospheric science, but they are often improperly applied due to lack of consideration or inappropriate handling of measurement uncertainty. In this work, numerical experiments are performed to evaluate the performance of five linear regression techniques, significantly extending previous works by Chu and Saylor. The five techniques are ordinary least squares (OLS), Deming regression (DR), orthogonal distance regression (ODR), weighted ODR (WODR), and York regression (YR). We first introduce a new data generation scheme that employs the Mersenne twister (MT) pseudorandom number generator. The numerical simulations are also improved by (a) refining the parameterization of nonlinear measurement uncertainties, (b) inclusion of a linear measurement uncertainty, and (c) inclusion of WODR for comparison. Results show that DR, WODR and YR produce an accurate slope, but the intercept by WODR and YR is overestimated and the degree of bias is more pronounced with a low R2 XY dataset. The importance of a properly weighting parameter λ in DR is investigated by sensitivity tests, and it is found that an improper λ in DR can lead to a bias in both the slope and intercept estimation. Because the λ calculation depends on the actual form of the measurement error, it is essential to determine the exact form of measurement error in the XY data during the measurement stage. If a priori error in one of the variables is unknown, or the measurement error described cannot be trusted, DR, WODR and YR can provide the least biases in slope and intercept among all tested regression techniques. For these reasons, DR, WODR and YR are recommended for atmospheric studies when both X and Y data have measurement errors. An Igor Pro-based program (Scatter Plot) was developed to facilitate the implementation of error-in-variables regressions.

Intercalibration of Polar-Orbiting Spectral Radiometers Without Simultaneous Observations

A new intercalibration method for two polar-orbiting satellite instruments or two instrument constellations’ Fundamental Climate Data Records (FCDRs) is presented. It is based on statistical fitting of reflectance data from the two instruments covering the same area during the same period, but not simultaneously. A Deming regression with iterative weights is used. The accuracy of the intercalibration method itself was better than 0.5% for the Moderate Resolution Imaging Spectroradiometer (MODIS) versus MODIS and Advanced Very High Resolution Radiometer (AVHRR) versus AVHRR test data sets. The intercalibration of an AVHRR FCDR generated by NOAA versus a combined MODIS Terra and Aqua data set of red and near-infrared (NIR) channels was carried out and showed a difference in the reflectance values of about 2% (red) and 6% (NIR). The presented intercalibration method can be used for checking the calibration of two instruments or FCDRs in all viewing angles used separately.

Automated skeletal tissue quantification in the lower leg using peripheral quantitative computed tomography

Objective: In this paper we introduce a methodology for hard and soft tissue quantification at proximal, intermediate and distal tibia sites using peripheral quantitative computed tomography scans. Quantification of bone properties is crucial for estimating bone structure resistance to mechanical stress and adaptations to loading. Soft tissue variables can be computed to investigate muscle volume and density, muscle-bone relationship, and fat infiltration. Approach: We employed implicit active contour models and clustering techniques for automated segmentation and identification of bone, muscle and fat at , , and tibia length. Next, we calculated densitometric, area and shape characteristics for each tissue type. We implemented our approach as a multi-platform tool denoted by TIDAQ (tissue identification and quantification) to be used by clinical researchers. Main results: We validated the proposed method against reference quantification measurements and tissue delineations obtained by semi-automated workflows. The average Deming regression slope between the tested and reference method was 1.126 for cross-sectional areas and 1.078 for mineral densities, indicating very good agreement. Our method produced high average coefficient of variation (R2) estimates: 0.935 for cross-sectional areas and 0.888 for mineral densities over all tibia sites. In addition, our tissue segmentation approach achieved an average Dice coefficient of 0.91 over soft and hard tissues, indicating very good delineation accuracy. Significance: Our methodology should allow for high throughput, accurate and reproducible automatic quantification of muscle and bone characteristics of the lower leg. This information is critical to evaluate risk of future adverse outcomes and assess the effect of medications, hormones, and behavioral interventions aimed at improving bone and muscle strength.

An Alternative Technique for Determining Gravimetric Particle Mass Deposition on Filter Substrate: The Particle Extraction Method

Airborne particulate matter (PM) filter sample processing is susceptible to error and can present issues associated with organizing samples, tracking data, and maintaining weighing conditions. While filter weighing facilities should implement robust quality assurance and control checks to ensure that data collection is accurate and filter storage is secure, mistakes and accidents can still occur that compromise valuable data. This paper presents a novel approach to PM filter sample processing that allows for data validation or data recovery while ensuring data integrity. The technique approximates the original, unused pre-sampling weight of polytetrafluoroethylene (PTFE) filters after PM collection to determine PM mass-deposition (MD). The method describes the extraction of PM loaded on PTFE filters via sonication in relatively non-toxic solvents, methanol and distilled water. The extraction method is compared to the standard gravimetric PM MD determination method for a set of 265 PTFE filters with mean post-sampling filter mass of 116 ± 3.6 mg, mean estimated PM MD using the standard method of 367 ± 589 μg, and mean estimated PM MD using the extraction method of 371 ± 589 μg. A Deming regression comparison of the two methods yields a slope of 0.9983 and a Pearson’s r of 0.999. A Bland-Altman assessment of the percent and absolute differences between the two methods shows the limits of agreement between 32.5% and 25.5% and -61.9 and 50.1 μg, respectively. The 99% confidence interval of the mean difference in mass deposition between the two methods is -5.8 ± 4.5 μg. These data demonstrate that estimating pre-sampling PTFE filter mass by extracting PM from sampled filters is a viable technique for gravimetric filter analysis. This method is of use in recovering pre-sampling filter weights that have been lost, incorrectly measured, or otherwise compromised.

Rivaroxaban Levels in Patients' Plasmas are Comparable by Using Two Different Anti Xa Assay/Coagulometer Systems Calibrated with Two Different Calibrators.

Rivaroxaban oral anticoagulant does not need laboratory monitoring, but in some situations plasma level measurement is useful. The objective of this paper was to verify analytical performance and compare two rivaroxaban calibrated anti Xa assays/coagulometer systems with specific or other branch calibrators. In 59 samples drawn at trough or peak from patients taking rivaroxaban, plasma levels were measured by HemosIL Liquid anti Xa in ACLTOP 300/500, and STA liquid Anti Xa in TCoag Destiny Plus. HemosIL and STA rivaroxaban calibrators and controls were used. CLSI guideline procedures EP15A3 for precision and trueness, EP6 for linearity, and EP9 for methods comparison were used. Coefficient of variation within run and total precision (CVR and CVWL respectively) of plasmatic rivaroxaban were < 4.2 and < 4.85% and BIAS < 7.4 and < 6.5%, for HemosIL-ACL TOP and STA-Destiny systems, respectively. Linearity verification 8 - 525 ng/mL a Deming regression for methods comparison presented R 0.963, 0.968 and 0.982, with a mean CV 13.3% when using different systems and calibrations. The analytical performance of plasma rivaroxaban was acceptable in both systems, and results from reagent/coagulometer systems are comparable even when calibrating with different branch material.

Performance of non-traditional hyperglycemia biomarkers by chronic kidney disease status in older adults with diabetes: Results from the Atherosclerosis Risk in Communities Study.

In people with chronic kidney disease (CKD), HbA1c may be a problematic measure of glycemic control. Glycated albumin and fructosamine have been proposed as better markers of hyperglycemia in CKD. In the present study we investigated associations of HbA1c, glycated albumin, and fructosamine with fasting glucose by CKD categories. A cross-sectional analysis was performed of 1665 Atherosclerosis Risk in Communities Study participants with diagnosed diabetes aged ≥65 years. Spearman's rank correlations (r) were compared and Deming regression was used to obtain root mean square errors (RMSEs) for the associations across CKD categories defined using estimated glomerular filtration rate and urine albumin:creatinine ratio. Correlations of HbA1c, glycated albumin, and fructosamine with fasting glucose were lowest in people with severe CKD (HbA1c r = 0.52, RMSE = 0.91; glycated albumin r = 0.39, RMSE = 1.89; fructosamine r = 0.41, RMSE = 1.87) and very severe CKD (r = 0.48 and RMSE = 1.01 for HbA1c; r = 0.36 and RMSE = 2.14 for glycated albumin; r = 0.36 and RMSE = 2.22 for fructosamine). Associations of glycated albumin and fructosamine with HbA1c were relatively similar across CKD categories. In older adults with severe or very severe CKD, HbA1c, glycated albumin, and fructosamine were not highly correlated with fasting glucose. The results suggest there may be no particular advantage of glycated albumin or fructosamine over HbA1c for monitoring glycemic control in CKD.

Harmonization of laboratory results by data adjustment in multicenter clinical trials

Background/AimsIn multicenter clinical trials, laboratory tests are performed in the laboratory of each center, mostly using different measuring methodologies. The purpose of this study was to evaluate coefficients of variation (CVs) of laboratory results produced by various measuring methods and to determine whether mathematical data adjustment could achieve harmonization between the methods.MethodsWe chose 10 clinical laboratories, including Green Cross Laboratories (GC Labs), the central laboratory, for the measurement of total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), serum triglycerides, creatinine, and glucose. The serum panels made with patient samples referred to GC Labs were sent to the other laboratories. Twenty serum samples for each analyte were prepared, sent frozen, and analyzed by each participating laboratory.ResultsAll methods used by participating laboratories for the six analytes had traceability by reference materials and methods. When the results from the nine laboratories were compared with those from GC Labs, the mean CVs for total cholesterol, HDL-C, LDL-C, and glucose analyzed using the same method were 1.7%, 3.7%, 4.3%, and 1.7%, respectively; and those for triglycerides and creatinine analyzed using two different methods were 4.5% and 4.48%, respectively. After adjusting data using Deming regression, the mean CV were 0.7%, 1.4%, 1.8%, 1.4%, 1.6%, and 0.8% for total cholesterol, HDL-C, LDL-C, triglyceride, creatinine, and glucose, respectively.ConclusionsWe found that more comparable results can be produced by laboratory data harmonization using commutable samples. Therefore, harmonization efforts should be undertaken in multicenter trials for accurate data analysis (CRIS number; KCT0001235).

Pooled Analysis of Multiple Crossover Trials To Optimize Individual Therapy Response to Renin-Angiotensin-Aldosterone System Intervention.

In the treatment of CKD, individual patients show a wide variation in their response to many drugs, including renin-angiotensin-aldosterone system inhibitors (RAASi). To investigate whether therapy resistance to RAASi can be overcome by uptitrating the dose of drug, changing the mode of intervention (with drugs from similar or different classes), or lowering dietary sodium intake, we meta-analyzed individual responses to different modes of interventions. Randomized crossover trials were analyzed to assess correlation of individual responses to RAASi and nonsteroidal anti-inflammatory drugs (NSAIDs; n=395 patients). Included studies compared the antialbuminuric effect of uptitrating the dose of RAASi (n=10 studies) and NSAIDs (n=1), changing within the same class of RAASi (e.g., angiotensin-converting enzyme inhibition to angiotensin receptor blockers; n=5) or NSAIDs (n=1), changing from RAASi to NSAIDs (n=2), and changing from high to low sodium intake (n=5). A two-stage meta-analysis was conducted: Deming regression was conducted in each study to assess correlations in response, and individual study results were then meta-analyzed. The albuminuria response to one dose of RAASi or NSAIDs positively correlated with the response to a higher dose of the same drug (r=0.72; 95% confidence interval [95% CI], 0.66 to 0.78), changes within the same class of RAASi or NSAIDs (r=0.54; 95% CI, 0.35 to 0.68), changes between RAASi and NSAIDs (r=0.44; 95% CI, 0.16 to 0.66), and changes from high to moderately low salt intake (r=0.36; 95% CI, 0.22 to 0.48). Results were similar when the individual systolic BP and potassium responses were analyzed, and were consistent in patients with and without diabetes. Individuals who show a poor response to one dose or type of RAASi also show a poor response to higher doses, other types of RAASi or NSAIDs, or a reduction in dietary salt intake. Whether other drugs or drug combinations targeting pathways beyond the renin-angiotensin-aldosterone system and prostaglandins would improve the individual poor response requires further study.

Agreement Between the 6 Seconds and 10 Seconds Exhalation Modes When Measuring Fractional Exhaled Nitric Oxide in Children Aged 4-6 Years With the NIOX VERO Device

SESSION TITLE: Pediatrics SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: NIOX VERO has the capability to measure fractional exhaled nitric oxide (FeNO) using both the 6 second (6s) and the 10 second (10s) exhalation modes. ATS/ERS 2005 guidelines for measurement of FeNO in children require exhalation of at least 4 seconds for children <12 years of age and >6 seconds for children >12 years of age. This study was undertaken to compare results of FeNO measurements performed using the 6s and 10s exhalation modes in children 4-6 years of age. METHODS: This was a randomized, multi-center, single-visit study with healthy and asthmatic children 4 to 6 years of age. Subjects were randomized to perform FeNO measurements starting with either the 6s or 10s exhalation mode. Data are presented in which the degree of agreement of FeNO measurements using the 6s and the 10s exhalation modes was assessed by weighted Deming regression analysis. RESULTS: The total population (n=247) consisted of 137 (55.5%) males, had a mean height of 112.8 cm, and was composed of 73 four year olds (4yo), 87 five year olds (5yo) and 87 six year olds (6yo). 105 subjects completed one FeNO measurement in either mode (20 4yo, 40 5yo, 45 6yo). An additional 88 subjects completed one FeNO measurement in either mode but were discontinued because enrollment into the low FeNO group (<20 ppb) was met (25 4yo, 30 5yo, 33 6yo). 54 subjects were unable to complete any FeNO measurements (28 4yo, 17 5yo, 9 6yo). There were 83 subjects that completed one FeNO measurement in both modes. Average FeNO values for the 6s (21.3 ppb) and the 10s (21.0 ppb) modes were comparable and paired differences between the replicates centered around zero for each age group. The 4yo mean paired difference was -0.3 (n=13, SD=1.58, median=0.0). The 5yo mean paired difference was 0.5 (n=31, SD=3.61, median=0.5). The 6yo mean paired difference was 0.4 (n=39, SD=3.70, median=0.5). Of the 83 subjects, 68 completed two FeNO measurements in both modes. Average FeNO values for the 6s (21.1 ppb) and the 10s (20.7 ppb) modes were comparable and paired differences between the replicates centered around zero for each age group. The 4yo mean paired difference was 0.4 (n=9, SD=0.74, median=0.0). The 5yo mean paired difference was 0.6 (n=27, SD=3.28, median=0.5). The 6yo mean paired difference was 0.1 (n=32, SD=3.99, median=0.3). The estimated intercept and slope from the weighted Deming regression modeling 6s mode FeNO results as a function of the 10s mode FeNO results were not significantly different from 0 and 1.0, respectively. Average bias in the predicted 6s mode FeNO results expressed as a percent of the 10s mode FeNO result was low (1.03%), and the bias at the 35 ppb cut-off value (0.391) was significantly less than 7 ppb (20% of 35 ppb; p<0.0001). FeNO values were within the tolerance limits at the 35 ppb cut-off value for 65/68 subjects (95.6%). There were no reported adverse events or serious injuries. CONCLUSIONS: The results of this study demonstrate that the degree of agreement between the 6s and 10s modes was high and that the NIOX VERO was safe in children 4-6 years of age. CLINICAL IMPLICATIONS: Performing FeNO measurements to assess TH2 inflammation in the airway using the 6s mode is a feasible option and can provide valuable information in the management of asthma in children 4-6 years of age. DISCLOSURE: Kathy Rickard: Employee: salary Margot MacDonald-Berko: Employee: salary Robert Anolik: Grant monies (from industry related sources): contract for study-related tasks Neal Jain: Grant monies (from industry related sources): contract for study-related tasks, Consultant fee, speaker bureau, advisory committee, etc.: contract for advisory board and speaker fees Craig La Force: Grant monies (from industry related sources): contract for study-related tasks, Consultant fee, speaker bureau, advisory committee, etc.: contract for speaker fees Richard Wasserman: Grant monies (from industry related sources): contract for study-related tasks The use of the NIOX VERO 6s exhalation mode and the use of the NIOX VERO in children younger than 7 years of age are uses not yet cleared by the FDA. However, the results of this study have been submitted to the FDA for 510k and clearances may be obtained prior to the CHEST meeting.

Improving validation methods for molecular diagnostics: application of Bland-Altman, Deming and simple linear regression analyses in assay comparison and evaluation for next-generation sequencing

AimsA standard approach in test evaluation is to compare results of the assay in validation to results from previously validated methods. For quantitative molecular diagnostic assays, comparison of test values...

Bioimpedance analysis vs. DEXA as a screening tool for osteosarcopenia in lean, overweight and obese Caucasian postmenopausal females.

We aimed at evaluating the efficiency of a newly developed, advanced Bioimpedance Analysis (BIA-ACC®) device as a screening tool for determining the degree of obesity and osteosarcopenia in postmenopausal women with normal or decreased bone density determined by Dual-Energy X-Ray absorptiometry (DEXA) in a representative sample of Greek postmenopausal women. This is a single-gate cross-sectional study of body composition measured by BIA-ACC® and DEXA. Postmenopausal females with BMI ranging from 18.5 to 40 kg/m2 were subjected to two consecutive measurements of DEXA and BIA-ACC® within 5-10 minutes of each other. We used Pearson's co-efficient to examine linear correlations, the intraclass correlation co-efficient (ICC) to test reliability, Bland-Atman plots to assess bias and Deming regressions to establish the agreement in parameters measured by BIA-ACC® and DEXA. Last, we used ANOVA, with Bonferroni correction and Dunnett T3 post hoc tests, for assessing the differences between quantitative and Pearson's x2 between qualitative variables. Our sample consisted of 84 overweight/obese postmenopausal women, aged 39-83 years, of whom 22 had normal bone density, 38 had osteopenia and 24 had osteoporosis based on DEXA measurements, using quota sampling. ICCs and Deming regressions showed strong agreement between BIA-ACC® and DEXA and demonstrated minimal proportional differences of no apparent clinical significance. Bland-Altman plots indicated minimal biases. Fat, skeletal and bone mass measured by BIA-ACC® and DEXA were increased in the non-osteopenic/non-osteoporotic women compared with those of the osteopenic and osteoporotic groups. BIA-ACC® is a rapid, bloodless and useful screening tool for determining body composition adiposity and presence of osteo-sarcopenic features in postmenopausal women. Women with osteopenia and osteoporosis evaluated by DEXA had decreased fat, skeletal and bone mass compared with normal bone density women, suggesting concordance in the change of these three organ masses in postmenopausal women.

Performance Assessment of a Trypanosoma cruzi Chimeric Antigen in Multiplex Liquid Microarray Assays

Diagnosing chronic Chagas disease (CD) requires antibody-antigen detection methods, which are traditionally based on enzymatic assay techniques whose performance depend on the type and quality of antigen used. Previously, 4 recombinant chimeric proteins from the Instituto de Biologia Molecular do Paraná (IBMP-8.1 to 8.4) comprising immuno-dominant regions of diverse Trypanosoma cruzi antigens showed excellent diagnostic performance in enzyme-linked immunosorbent assays. Considering that next-generation platforms offer improved CD diagnostic accuracy with different T. cruzi-specific recombinant antigens, we assessed the performance of these chimeras in liquid microarrays (LMAs). The chimeric proteins were expressed in Escherichia coli and purified by chromatography. Sera from 653 chagasic and 680 healthy individuals were used to assess the performance of these chimeras in detecting specific anti-T. cruzi antibodies. Accuracies ranged from 98.1 to 99.3%, and diagnostic odds ratio values were 3,548 for IBMP-8.3, 4,826 for IBMP-8.1, 7,882 for IBMP-8.2, and 25,000 for IBMP-8.4. A separate sera bank (851 samples) was employed to assess cross-reactivity with other tropical diseases. Leishmania, a pathogen with high similarity to T. cruzi, showed cross-reactivity rates ranging from 0 to 2.17%. Inconclusive results were negligible (0 to 0.71%). Bland-Altman and Deming regression analysis based on 200 randomly selected CD-positive and negative samples demonstrated interchangeability with respect to CD diagnostic performance in both singleplex and multiplex assays. Our results suggested that these chimeras can potentially replace antigens currently used in commercially available assay kits. Moreover, the use of multiplex platforms, such as LMA assays employing 2 or more IBMP antigens, would abrogate the need for 2 different testing techniques when diagnosing CD.

The relationship between minute ventilation and end tidal CO2 in intubated and spontaneously breathing patients undergoing procedural sedation.

BackgroundMonitoring respiratory status using end tidal CO2 (EtCO2), which reliably reflects arterial PaCO2 in intubated patients under general anesthesia, has often proven both inaccurate and inadequate when monitoring non-intubated and spontaneously breathing patients. This is particularly important in patients undergoing procedural sedation (e.g., endoscopy, colonoscopy). This can be undertaken in the operating theater, but is also often delivered outside the operating room by non-anesthesia providers. In this study we evaluated the ability for conventional EtCO2 monitoring to reflect changes in ventilation in non-intubated surgical patients undergoing monitored anesthesia care and compared and contrasted these findings to both intubated patients under general anesthesia and spontaneously breathing volunteers.MethodsMinute Ventilation (MV), tidal volume (TV), and respiratory rate (RR) were continuously collected from an impedance-based Respiratory Volume Monitor (RVM) simultaneously with capnography data in 160 patients from three patient groups: non-intubated surgical patients managed using spinal anesthesia and Procedural Sedation (n = 58); intubated surgical patients under General Anesthesia (n = 54); and spontaneously breathing Awake Volunteers (n = 48). EtCO2 instrument sensitivity was calculated for each patient as the slope of a Deming regression between corresponding measurements of EtCO2 and MV and expressed as angle from the x-axis (θ). All data are presented as mean ± SD unless otherwise indicated.ResultsWhile, as expected, EtCO2 and MV measurements were negatively correlated in most patients, we found gross systematic differences across the three cohorts. In the General Anesthesia patients, small changes in MV resulted in large changes in EtCO2 (high sensitivity, θ = -83.6 ± 9.9°). In contrast, in the Awake Volunteers patients, large changes in MV resulted in insignificant changes in EtCO2 (low sensitivity, θ = -24.7 ± 19.7°, p < 0.0001 vs General Anesthesia). In the Procedural Sedation patients, EtCO2 sensitivity showed a bimodal distribution, with an approximately even split between patients showing high EtCO2 instrument sensitivity, similar to those under General Anesthesia, and patients with low EtCO2 instrument sensitivity, similar to the Awake Volunteers.ConclusionsWhen monitoring non-intubated patients undergoing procedural sedation, EtCO2 often provides inadequate instrument sensitivity when detecting changes in ventilation. This suggests that augmenting standard patient care with EtCO2 monitoring is a less than optimal solution for detecting changes in respiratory status in non-intubated patients. Instead, adding direct monitoring of MV with an RVM may be preferable for continuous assessment of adequacy of ventilation in non-intubated patients.

Dried blood spot sampling of nilotinib in patients with chronic myeloid leukaemia: a comparison with venous blood sampling

To compare nilotinib concentrations obtained by venous blood sampling and dried blood spot (DBS) in patients with chronic myeloid leukaemia (CML). It was investigated how to predict nilotinib plasma levels on the basis of DBS. Forty duplicate DBS and venous blood samples were collected from 20 patients. Capillary blood was obtained by finger prick and spotted on DMPK-C Whatman sampling paper, simultaneously with venous blood sampling. Plasma concentrations were predicted from DBS concentrations using three methods: (1) individual and (2) mean haematocrit correction and (3) the bias between plasma and DBS concentrations. Results were compared using Deming regression and Bland-Altman analysis. Nilotinib plasma concentrations ranged from 376 to 2663μg/l. DBS concentrations ranged from 144 to 1518μg/l. The slope was 0.56 (95% CI, 0.51 to 0.61) with an intercept of -41.68μg/l (95% CI, -93.78 to 10.42). Mean differences between calculated and measured plasma concentrations were -14.3% (method 1), -14.0% (method 2) and -0.6% (method 3); differences were within 20% of the mean in 73%, 85% and 80% of the samples, respectively. The slopes were respectively 0.96 (95% CI, 0.86 to 1.06), 0.95 (95% CI, 0.86 to 1.03) and 1.00 (95% CI, 0.91 to 1.09). Plasma concentrations of nilotinib could be predicted on the basis of DBS. DBS sampling to assess nilotinib concentrations in CML patients seems a suitable alternative for venous sampling.

Characterization of the analytic performance of an electrochemical point-of-care meter for measuring β-hydroxybutyrate concentration in blood and plasma from periparturient dairy cattle.

The Precision Xtra electrochemical meter is widely used to measure blood β-hydroxybutyrate concentration (BHBb) in dairy cattle. The meter uses an algorithm optimized for human blood that assumes the HCT in cattle is the same as in people, and that intra-erythrocyte β-hydroxybutyrate (BHBe) and plasma β-hydroxybutyrate (BHBp) concentration are equivalent. The first objective was to characterize the analytic performance of the meter for measuring BHBb and BHBp in dairy cattle. The second objective was to characterize the influence of HCT and sample temperature on BHBp concentration measured by the meter. Blood and plasma samples were obtained from 106 periparturient Holstein cattle and 15 lactating Holstein cows with experimentally induced electrolyte and acid-base imbalances. Meter performance was evaluated using Deming regression and Bland-Altman plots. Multivariable linear regression was used to determine the effect of HCT and sample temperature on BHBb and BHBp concentration, respectively. The meter was linear up to BHB = 3.0 mmol/L as measured by the reference method, equivalent to meter values for BHBb > 4.5 mmol/L and BHBp > 5.2 mmol/L. An increase in HCT resulted in higher BHBb concentration. This result was partially explained by BHBe being much lower than BHBp. Changes in sample temperature caused a linear change in measured BHBp whenever BHBp > 3.0 mmol/L. Meter accuracy was markedly dependent on the BHBe-to-BHBp ratio and consequently the HCT. Therefore, the algorithm used by the meter should be revised when applied to bovine blood for improved accuracy.

A validation method for near-infrared spectroscopy based tissue oximeters for cerebral and somatic tissue oxygen saturation measurements

We describe the validation methodology for the NIRS based FORE-SIGHT ELITE® (CAS Medical Systems, Inc., Branford, CT, USA) tissue oximeter for cerebral and somatic tissue oxygen saturation (StO2) measurements for adult subjects submitted to the United States Food and Drug Administration (FDA) to obtain clearance for clinical use. This validation methodology evolved from a history of NIRS validations in the literature and FDA recommended use of Deming regression and bootstrapping statistical validation methods. For cerebral validation, forehead cerebral StO2 measurements were compared to a weighted 70:30 reference (REF CXB) of co-oximeter internal jugular venous and arterial blood saturation of healthy adult subjects during a controlled hypoxia sequence, with a sensor placed on the forehead. For somatic validation, somatic StO2 measurements were compared to a weighted 70:30 reference (REF CXS) of co-oximetry central venous and arterial saturation values following a similar protocol, with sensors place on the flank, quadriceps muscle, and calf muscle. With informed consent, 25 subjects successfully completed the cerebral validation study. The bias and precision (1 SD) of cerebral StO2 compared to REF CXB was −0.14 ± 3.07%. With informed consent, 24 subjects successfully completed the somatic validation study. The bias and precision of somatic StO2 compared to REF CXS was 0.04 ± 4.22% from the average of flank, quadriceps, and calf StO2 measurements to best represent the global whole body REF CXS. The NIRS validation methods presented potentially provide a reliable means to test NIRS monitors and qualify them for clinical use.

Whole blood selenium determination by inductively coupled plasma mass spectrometry

ObjectiveTo develop a sensitive method for accurately measuring whole blood selenium and determining an appropriate reference interval for the local Cleveland population. Design and methodsThe assay was developed and validated on an inductively coupled plasma mass spectrometry (ICP-MS) with a collision cell. Whole blood trace element free EDTA tubes were used to collect samples for the reference interval study (n=50). Samples were collected after at least 8h fast from healthy adults (76% females) with ages between 19 and 64yr. Whole blood aliquots (1mL) in acid washed cryogenic vials were stored at −70°C until analysis. ResultsThe method passed the matrix effect, interference (except for Gd), and carryover tests. The method had a linear range of 0.2–7.1μmol/L with accuracies of 87.1–118.1%. The total assay imprecision (CV) was <2.5% across the concentration levels tested. Comparison to another ICP-MS assay offered by an independent clinical lab yielded a Deming regression with a slope of 0.98, an intercept of 0.1μmol/L, a standard error of estimate of 0.1μmol/L, a correlation coefficient of 0.9846, and an average difference of 0.8%. The whole blood Se reference interval using a transformed parametric method was 2.2–3.5μmol/L. ConclusionsThis whole blood Se ICP-MS methodology is sensitive and acceptable for patient testing.

Retrospective Analysis of Point-of-Care and Laboratory-Based Hemoglobin A1c Testing.

Glycemic control is essential to diabetic management, and hemoglobin A1c (Hb A1c) has long been used for this purpose. Though laboratory-based testing is standard, point-of-care (POC) systems provide rapid results in clinic, allowing more timely patient management. A negative bias with POC testing has been observed, and our aim is to further characterize these discrepancies at our institution. A medical record search identified patients who underwent laboratory-based and/or POC Hb A1c testing (DCA Vantage™) at our medical center from July 2015 to April 2016. Patients who underwent both tests within 30 days were grouped by age, sex, and test interval (same day, <1 day, ≤15 days, or ≤30 days). Mean laboratory-based and POC values were compared using the paired t-test. Correlation statistics were determined using the Deming regression. In total, 40503 data points were gathered from the database, comprising 28555 laboratory-based Hb A1c tests and 11948 POC-based Hb A1c tests. A total of 28292 unique patients were identified, of which 493 underwent both tests within 30 days. While DCA and laboratory-based testing was highly correlated, there was a mean negative bias of 0.18% with POC testing. Bias was greater for women [0.17% higher (95% CI, 0.063%-0.284%), P = 0.002] and children aged 0-13 years [0.52% higher (95% CI, 0.141%-0.891%), P = 0.007]. There is a consistent negative bias with POC testing, most pronounced in the female and pediatric populations. Further studies will determine what variables contribute to this discrepancy and how clinical management is modified. POC testing using the DCA Vantage should be interpreted cautiously.