Significant Proportional Bias Research Articles

Evaluation of a new soluble transferrin receptor assay and comparison to three measurement procedures.

Soluble transferrin receptor (sTfR) is a useful marker in the differentiation of anemia. Clinical utility is limited by lack of standardization between measurement procedures and interpretative recommendations. Our objective was to evaluate the analytical performance of a research sTfR immunoturbidimetric assay (Alinity c, Abbott Diagnostics) and compare it to three established measurement procedures. Assay imprecision was assessed with 7 panels across the analytical measuring interval. 159 patient samples were measured across four instrument systems (Alinity c [Abbott Diagnostics], Tina-quant c502 [Roche Diagnostics], Quantex Biokit [Werfen], and ACCESS [Beckman Coulter]). Ferritin was also measured to calculate an sTfR/Log Ferritin ratio. Sera from 100 reference individuals were assayed for sTfR and ferritin (Alinity) for reference interval (RI) verification (sTfR) or establishment (sTfR index). Assay imprecision met defined goals. Method comparison between Alinity c and ACCESS sTfR assays showed good agreement (slope: 1.06, intercept: -0.12, r: 0.989). Comparisons across other assays demonstrated significant proportional bias with slopes ranging from 0.44 (Tina-quant c502, mean bias: -2.52 mg/L) to 1.24 (Quantex Biokit, mean bias: 0.60 mg/L). A proportional bias was observed between other instruments. While the sTfR RI was verified on the Alinity assay, agreement in interpretation (within vs outside RI) between Alinity and other platforms ranged from 74.2-80.5 %. We report the first characterization of the performance of a research sTfR immunoturbidimetric assay (Alinity c, Abbott Diagnostics). Our findings emphasize the lack of harmonization between measurement procedures and result interpretation for sTfR and sTfR index, necessitating standardization efforts and clinical studies.

Fractional flow reserve measurement using dynamic CT perfusion imaging in patients with coronary artery disease

Fractional flow reserve measurement using dynamic CT perfusion imaging in patients with coronary artery disease

Minimal coronary microvascular resistance: agreement between continuous and bolus thermodilution

Abstract Background Continuous thermodilution quantifies absolute microvascular resistance (Rµ, Woods units), the quintessential metric of microvascular function. Rµ is minimal during hyperaemia (Rµ,hyper) with increased Rµ,hyper suggestive of microvascular dysfunction. Bolus thermodilution measures the index of microcirculatory resistance (IMR), a dimensionless surrogate of Rµ,hyper. Purpose We compared Rµ,hyper measured by continuous thermodilution (invasive Rµ,hyper) with the gold standard [15O]H2O positron emission tomography (PET Rµ,hyper), and explored the correlation between invasive Rµ,hyper and uncorrected IMR. Methods The accuracy of invasive Rµ,hyper was assessed in a cohort of 24 patients in which both invasive and PET Rµ,hyper were measured (cohort 1). For both techniques, Rµ,hyper was assessed in both the left anterior descending artery (LAD) and the circumflex artery (LCX), corresponding to 46 measurement of Rµ,hyper in total (LAD=24, LCX=22). Agreement between invasive Rµ,hyper and IMR was evaluated in a cohort of 250 patients with angina and non-obstructive coronary arteries (ANOCA) evaluated in 3 European centres (cohort 2). All measurements in this cohort were performed in the LAD, with patients randomly assigned in a 1:1 ratio to undergo either bolus or continuous thermodilution first. Both techniques were performed by the same operator during the same procedure with a strict interval of 5 minutes between techniques. Results In cohort 1, invasive Rµ,hyper exhibited a strong correlation with PET Rµ,hyper (r=0.86 [95% CI 0.76-0.92], p<0.001), with excellent absolute agreement (ICC 0.82 [95% CI 0.70-0.90], p<0.001) (Figure 1). Furthermore, Passing-Bablok regression analysis found no significant systematic (intercept A: 54.53 [95% CI -18.95 to 120.96]) or proportional (slope B: 0.90 [95% CI 0.71 to 1.15]) bias between invasive Rµ,hyper and PET Rµ,hyper. However, in cohort 2, invasive Rµ,hyper exhibited no significant correlation with IMR (r=0.11 [95% CI -0.01 to 0.23], p=0.08) (Figure 2). Conclusion Invasive Rµ,hyper derived from continuous thermodilution exhibited excellent agreement with non-invasive Rµ,hyper measured by [15O]H2O PET, the current standard of reference. However, IMR exhibited no significant correlation with invasive Rµ,hyper in patients with stable coronary syndromes.Figure 1.PET vs invasive Rµ,hyperFigure 2.Invasive Rµ,hyper vs IMR

A-020 Evaluation of the QuidelOrtho Diagnostics Vitros NT-proBNP II Assay

Abstract Background N-terminal-proBNP (NT-proBNP), a short peptide originating from the cleavage of proBNP by Corin, can be used as a diagnostic test in individuals presenting with signs and symptoms consistent with heart failure (HF). QuidelOrtho Diagnostics released its latest reformulation of its NT-proBNP assay, the Vitros NT-proBNP II assay. The analytical performance of this assay was evaluated. Methods Repeatability, reproducibility, and carryover were assessed using quality control material. The analytical measuring range and clinical reportable range (AMR and CRR) were assessed using commercially available material and diluted patient samples. Accuracy was assessed by comparing results from the Vitros NT-proBNP II assay and results from the Vitros NT-proBNP assay. Instrument-to-instrument comparison was performed by comparing results from the NT-proBNP II assay from two different Vitros 5600 chemistry analyzers. Paired heparin and EDTA plasma samples were assessed for specimen type comparison. Results Repeatability and reproducibility were <=10% CV and no carryover was observed. The AMR was 20 - 30,000 pg/mL and the CRR extended the range to 600,000 pg/mL. Passing-Bablok analysis showed a significant proportional bias with a slope of 1.34 for samples up to 12,000 pg/mL (Vitros NT-proBNP). Vendor-performed comparison studies showed no significant proportional bias with a slope of 1.06 using unweighted Deming analysis for samples up to 20,700 pg/mL (Vitros NT-proBNP). Instrument-to-instrument and heparin-to-EDTA plasma comparisons showed no significant biases. Conclusions The NTproBNP II assay showed acceptable repeatability, reproducibility, and no carryover. The AMR analysis verified the measuring range in the IFU of the assay and the CRR is extended to 600,000 pg/mL. Results were very comparable between two different Vitros 5600s and between paired heparin and EDTA plasma specimens. Comparison between the Vitros NT-proBNP and Vitros NT-proBNP II assays showed a very significant proportional bias (slope of 1.34) for specimens up to 12,000 pg/mL measured on the Vitros NT-proBNP assay, but the proportional bias is less significant at higher NT-proBNP values (>20,000 pg/mL, Vitros NT-proBNP) are included in the analysis. There may be a significant matrix effect or interference at lower NT-proBNP concentrations with the reformulated reagent, which may be less prominent when NT-proBNP is present at much higher concentrations.

A-138 Implications of native protein conformation in the IgM quantification: total Ig vs HLC methods comparison

Abstract Background For IgM monoclonal gammopathies such as Waldenström Macroglobulinemia, the diagnosis, risk stratification and monitoring response to therapy is based on the detection and quantification of the secreted IgM monoclonal protein. Accurate IgM measurement is challenging due to its complex nature and the occurrence in higher polymeric structures (i.e., pentamers or hexamers), as well as heterogeneity and inherent subjectivity of the selected common methodologies. The recently developed Heavy/Light chain assay (Binding Site, part of Thermofisher Scientific) allows the separate determination of the IgM-Kappa and IgM-Lambda molecules, offering an alternative method to the serum electrophoresis (SPE) with reported higher sensitivity (Ref. Boyle E. et al, Clin Cancer Research 2016). In this study we explore the effect of the molecular structure on 3 different analytical techniques for accurate IgM measurements Methods 214 serum samples from patients (age median 63yo) under follow-up at our hospital were tested for: IgG, IgA, and IgM levels (immunoturbidimetry, either on a Beckman Coulter AU5800 analyser; Nyon, Switzerland; or a Cobas c 702 system, Roche Diagnostics); Hevylite assay (on an Optilite, Binding Site); and SPE and Immunofixation (Capillarys 3 Octa and Hydrasys 2, Sebia Inc.). The effect of the molecular conformation was evaluated through sample depolymerization with N-Acetylcysteine (NAC) according to the manufacturer’s instruction (Sebia Inc.) and IgM quantification by: tIgM (immunoturbidimetric total Ig); red-Ig (idem after NAC reduction); and, HLC-Ig (i. e. sum of the IgM-K+IgM-L heavy/light chain pair measured by Hevylite (Binding Site)). Results Total-Ig, red-Ig, and HLC-Ig returned similar results for IgG and IgA immunoglobulins (Kruskal-Wallis test, p-value > 0.05), and Passing Bablok regression analysis showed good agreement between the three methods, except for higher IgA levels. In the later, both HLC-IgA levels red-IgA values were higher than total-IgA. Regarding the IgM, PB regression revealed a significant proportional bias, with obtained values approx. 2,5x higher by red-IgM and approx. 1,4x by HLC-IgM methods than tIgM (red-IgM=-5.5+2.42*tIgM, Spearman’s r=0.995; HLC-IgM=-0,77+1.34*tIgM, Spearman’s r=0.978; red-IgM=-6.29+1.82*HLC-IgM, Spearman’s r=0.98). So, both red-IgM and HLC-IgM results are higher than total IgM. Of note, 1 sample presented antigen excess, resulting in unusually low IgM levels by tIgM but high red-IgM and high HLC-IgM levels coherent with the patient’s clinical condition. 75 samples had monoclonal protein measurable by SPE, showing good correlation with the three methods, however with greater proportional errors between measurements with other techniques Conclusions IgM molecular conformational status may affect the epitopes exposed and, therefore, available for the different assays’ recognition. Higher IgM complexes depolymerization into monomeric conformation results in higher IgM levels, which agree better with the Hevylite than with the total IgM measured previous NAC reduction, reflecting the impact of the native protein conformation in the IgM precise detection. Although also affected by the conformational status, Hevylite IgM results were closer to the reduced IgM levels than the obtained by the total IgM assay, therefore offering a sensitive assay that does not need a reduction treatment for a more accurate IgM quantification, optimizing the laboratory workflow

Reproducibility of [18F]MK-6240 kinetics in brain studies with shortened dynamic PET protocol in healthy/cognitively normal subjects

Background[18F]MK-6240 is a neurofibrillary tangles PET radiotracer that has been broadly used in aging and Alzheimer’s disease (AD) studies. Majority of [18F]MK-6240 PET studies use dynamic acquisitions longer than 60 min to assess the tracer kinetic parameters. As of today, no consensus has been established on the optimum dynamic PET scan time. In this study, we assess the reproducibility of [18F]MK-6240 quantitative metrics using shortest dynamic PET protocols in cognitively normal subjects. PET metrics were measured through two-tissue compartment model (2TCM) and Logan model to estimate VT and DVR, as well as SUVR from 90 to 120 min (SUVR90 − 120 min) post-tracer injection for brain regions. 2TCM was carried out using the 120 min dynamic coffee break dataset (first scan from 0 to 60 min p.i., second scan from 90 to 120 min p.i.) and then repeated after stepwise shortening it by 5 min. The dynamic scan length that reproduced the 120 min dynamic scans-based VT to within 10% error was defined as the shortest acquisition time (SAT). The SAT SUVR90 − 120 min was deduced from the SAT dataset by extrapolation of each image pixel time-activity curve to 120 min. The reproducibility of the 120 min dynamic scans-based VT2TCM, DVR2TCM, DVRLogan, and SUVR using the SAT was assessed using Passing-Bablock analysis. The limits of reproducibility of each PET metrics were determined using Bland-Altman analysis.ResultsA dynamic SAT of 40 min yielded < 10% error in [18F]MK-6240 VT2TCM’s for all brain regions, compared to those measured using the 120 min datasets. SAT-based analysis did not show statistically significant systemic or proportional biases in VT2TCM, DVR2TCM, DVRLogan, or SUVR compared to those deduced from the full dynamic dataset of 120 min. A mean difference between the 120 min- and SAT-based analysis of less than 4%, 10%, 15%, and 20% existed in the VT2TCM, DVR2TCM, DVRLogan, and SUVR respectively.ConclusionKinetic modeling of [18F]MK-6240 PET can be accurately performed using dynamic scan times as short as 40 min. This can facilitate studies with [18F]MK-6240 PET and improve patients accrual. Further work would be necessary to confirm the reproducibility of these results for patients in dementia spectra.

Test-retest reliability and minimal detectable change in pelvis and lower limb coordination during running assessed with modified vector coding

The objective of this study was to evaluate the reliability of Modified Vector Coding in assessing the coordination and coordination variability of the lower limbs and pelvis during running and to determine the Minimal Detectable Change (MDC). Twenty-five healthy runners participated in a biomechanical analysis of treadmill running using a motion capture system. Modified vector coding was applied to assess the three-dimensional coordination among various pelvis and lower limb segmental couplings. Reliability was assessed using the Intraclass Correlation Coefficient (ICC), Standard Error of Measurement (SEM), MDC, and Bland-Altman analysis to ascertain measurement consistency, agreement, and the smallest clinically meaningful change that exceeds measurement error. The test–retest reliability for 33 of 42 segmental couplings analyzed was good to excellent, with ICC values ranging from 0.613 to 0.928 (p <0.05), which substantiates the robustness of modified vector coding in running biomechanics. However, nine couplings, particularly femur-tibia in the sagittal plane during midstance and foot in the frontal plane-tibia in the transverse plane during late stance, exhibited poor to moderate reliability. These findings underscore the need for cautious interpretation due to significant proportional bias (p <0.05). SEM and MDC provided insights into the precision and minimal clinically significant changes for each coupling. The findings confirm the reliability of modified vector coding for biomechanical analysis in running, with most couplings demonstrating consistent high reliability. Nevertheless, specific couplings should be interpreted with caution due to potential measurement errors. The application of MDC highlights the precision of modified vector coding in biomechanical analyses and emphasizes the importance of careful interpretation to improve clinical and research outcomes in running-related injuries.

Lack of Interchangeability Between 3 Different Methods for Quantification of Everolimus in Blood: ACMIA, LTIA, and UHPLC-MS/MS.

Affinity chrome-mediated immunoassays (ACMIA) do not require pretreatment and have a wide calibration range and good analytical performance. To date, no studies have compared ACMIA and latex agglutination turbidimetry immunoassays (LTIA). The objective of this study was to evaluate the interchangeability of ACMIA, LTIA, and the previously developed ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). A total of 111 whole blood samples were collected from 25 patients undergoing routine everolimus therapeutic drug monitoring. The interchangeability between the 3 methods was assessed using robust Passing-Bablok regression analysis and Bland-Altman plots. All samples were quantifiable by UHPLC-MS/MS, whereas 56 and 1 samples were below the lower limits of quantification by LTIA and ACMIA, respectively. In the robust Passing-Bablok regression plots, the slopes of the regression equations between ACMIA and UHPLC-MS/MS, LTIA and UHPLC-MS/MS, and ACMIA and LTIA were 1.23 (95% [confidence interval] CI, 1.13-1.33), 0.67 (95% CI, 0.57-0.77), and 1.71 (95% CI, 1.43-2.33), respectively, with significant proportional biases indicating no interchangeability among all 3 methods. Bland-Altman plots also revealed statistically significant proportional biases between ACMIA and UHPLC-MS/MS (P = 0.012), LTIA and UHPLC-MS/MS (P < 0.001), and ACMIA and LTIA (P < 0.001). Statistically significant proportional biases were observed among the 3 methods. Blood everolimus concentration measurements should be interpreted with caution when switching the quantification methods for therapeutic drug monitoring.

Evaluating a web-based visual acuity and refractive error self-assessment tool in myopic children.

Demands for myopia management are rising. A web-based tool that allows home-performed self-assessments of visual acuity (VA) and refractive error may enable hybrid care pathways and aid in identifying those with deteriorating visual performance. The tool has been validated in adult populations, but has yet to be evaluated in children. This study compared home-performed VA and refraction self-assessments to conventional measurements obtained at the clinic in a population of myopic children. Myopic children aged ≥6 years old were invited to perform web-based eye tests at home, assisted by a parent. At two myopia control clinics, they also underwent measurements of VA using a Snellen chart and refractive error using cycloplegic autorefraction. Agreement between the tests, repeatability of the web-based test and associations between clinical characteristics and web-based test accuracy were evaluated. A total of 147 children were enrolled, of whom 116 (51% male; mean age 13 ± 3 years; mean spherical equivalent refraction (SEQ) -5.58 ± 3.05) performed the web-based tests at home. Overall, the home-performed VA self-assessment and the Snellen chart assessment at the clinic agreed well (mean difference 0.03 ± 0.11 logMAR). A significant proportional bias was identified (β 0.65, p < 0.001), indicating underestimated web-based VA scores when the child's vision declined. The sensitivity to detect VA poorer than 0.10 logMAR was 94%; the specificity was 71%. The web-based refractive error algorithm measured more myopia progression compared to clinic observations (mean difference SEQ 0.40 ± 0.51 dioptres). Age, sex or use of atropine drops were not significantly associated with test accuracy. The web-based test for self-assessing vision, performed at home by children with assistance from their parents, yielded VA scores with a precision similar to Snellen chart testing conducted in a clinical setting. However, the web-based refractive error algorithm overestimated myopia progression and requires recalibration for this specific age group.

Measuring Vertical Jump Height With Artificial Intelligence Through a Cell Phone: A Validity and Reliability Report.

Erik, HT, Onn, SW, and Montalvo, S. Vertical jump height with artificial intelligence through a cell phone: a validity and reliability report. J Strength Cond Res 38(9): e529-e533, 2024-This study estimated the reliability and validity of an artificial intelligence (AI)-driven model in the My Jump 2 (My Jump Lab ) for estimating vertical jump height compared with the Force Platform (FP). The cross-sectional study involved 88 athletes (33 female and 55 male athletes), performing a total of 264 countermovement jumps with hands on hips. "Jump heights were simultaneously measured using the FP and the My Jump 2 app." The FP estimated jump heights using the impulse-momentum method, whereas My Jump 2 used the flight-time method, with the latter using an AI feature for automated detection of jump take-off and landing. Results indicated high reliability for the AI model (intraclass correlation coefficient [ICC 1,3 ] = 0.980, coefficient of variation [CV] = 4.12) and FP (ICC 1,3 = 0.990, CV = 2.92). Validity assessment showed strong agreement between the AI model and FP (ICC 2,k = 0.973). This was also supported by the Bland-Altman analysis, and the ordinary least products regression revealed no significant systematic or proportional bias. The AI-driven model in My Jump 2 is highly reliable and valid for estimating jump height. Strength and conditioning professionals may use the AI-based mobile app for accurate jump height measurements, offering a practical and efficient alternative to traditional methods.

Head-to-head comparison of four plasma neurofilament light chain (NfL) immunoassays

BackgroundNeurofilament Light Chain (NfL) is an emerging blood biomarker of neuro-axonal injury and neurodegeneration with the potential to be used in the clinical management of various neurological conditions. Various NfL immunoassays are in development on high-throughput automated systems, but little information is available related to the comparability between assays. In this study, we performed a head-to-head comparison of four NfL immunoassays using plasma samples from individuals with various neurological conditions. MethodsEDTA plasma samples in which NfL was ordered clinically were stratified according to diagnosis. NfL concentrations (pg/mL) in plasma were obtained using the Quanterix Simoa®, the Roche Elecsys, the Siemens Healthineers Atellica®IM, and the Fujirebio Lumipulse® NfL assays. Passing-Bablok regression analyses were performed to assess the correlation and bias between methods. Additionally, the distribution of NfL concentrations for each assay was assessed in three disease groups: amyotrophic lateral sclerosis (ALS) upon initial diagnosis, ALS treated, and multiple sclerosis (MS). ResultsThe R2 between assays were all ≥ 0.95, however, significant proportional bias was observed between some assays. In particular, the Roche Elecsys assay NfL concentrations were significantly lower (∼85 %) when compared against the other three assays. The four assays were comparable with regards to the percentage of patients that were identified as having an elevated NfL result in the various clinical groups: ALS initial diagnoses (83–94 %), ALS untreated (93–100 %), and MS (8–18 %). ConclusionsThis is the first study describing a head-to-head comparison of four automated NfL immunoassays. We demonstrate that there is a strong correlation between assays but a lack of standardization which is evident by the bias observed between some of the evaluated methods. These analytical differences will be important to consider when using NfL as a biomarker of neurodegeneration.

A novel integrated lateral flow immunoassay platform for the detection of cardiac troponin I using hierarchical dendritic copper-nickel nanostructures

Cardiac troponin I (cTnI) is a critical biomarker for the diagnosis of acute myocardial infarction (AMI). Herein, we report a novel integrated lateral flow immunoassay (LFIA) platform for highly sensitive point-of-care testing (POCT) of cTnI using hierarchical dendritic copper-nickel (HD-nanoCu-Ni) nanostructures. The electrodeposited HD-nanoCu-Ni film (∼22 μm thick) on an ITO-coated glass substrate exhibits superior capillary action and structural integrity. These properties enable efficient sample transport and antibody immobilization, making it a compelling alternative to conventional multi-component paper-based LFIA test strips, which are often plagued by structural fragility and susceptibility to moisture damage. The biofunctionalized HD-nanoCu-Ni substrates were laser-etched with lateral flow channels, including a sample loading/conjugate release zone, a test zone, and a control zone. Numerical simulations were used to further optimize the design of these channels to achieve optimal fluid flow and target capture. The HD-nanoCu-Ni LFIA device utilizes a fluorescence quenching based sandwich immunoassay format using antibody-labeled gold nanoparticles (AuNPs) as quenchers. Two different fluorescent materials, fluorescein isothiocyanate (FITC) and CdSe@ZnS quantum dots (QDs), were used as background fluorophores in the device. Upon the formation of a sandwich immunocomplex with cTnI on the HD-nanoCu-Ni device, introduced AuNPs led to the fluorescence quenching of the background fluorophores. The total assay time was approximately 15 min, demonstrating the rapid and efficient nature of the HD-nanoCu-Ni LFIA platform. For FITC, both inner filter effect (IFE) and fluorescence resonance energy transfer (FRET) contributed to the AuNP-mediated quenching. In the case of CdSe@ZnS QDs, IFE dominated the AuNP-induced quenching. Calibration curves were established based on the relationship between the fluorescence quenching intensity and cTnI concentration in human serum samples, ranging from 0.5 to 128 ng/mL. The limits of detection (LODs) were determined to be 0.27 ng/mL and 0.40 ng/mL for FITC and CdSe@ZnS QDs, respectively. A method comparison study using Passing-Bablok regression analysis on varying cTnI concentrations in human serum samples confirmed the equivalence of the HD-nanoCu-Ni LFIA platform to a commercial fluorescence cTnI LFIA assay kit, with no significant systematic or proportional bias observed.

Quantification of Aortic Valve Calcification in Contrast-Enhanced Computed Tomography.

Background: The goal of our study is to evaluate a method to quantify aortic valve calcification (AVC) in contrast-enhanced computed tomography for patients with suspected severe aortic stenosis pre-interventionally. Methods: A total of sixty-five patients with aortic stenosis underwent both a native and a contrast-enhanced computed tomography (CECT) scan of the aortic valve (45 in the training cohort and 20 in the validation cohort) using a standardized protocol. Aortic valve calcification was semi-automatically quantified via the Agatston score method for the native scans and was used as a reference. For contrast-enhanced computed tomography, a calcium threshold of the Hounsfield units of the aorta plus four times the standard deviation was used. Results: For the quantification of aortic valve calcification in contrast-enhanced computed tomography, a conversion formula (691 + 1.83 x AVCCECT) was derived via a linear regression model in the training cohort. The validation in the second cohort showed high agreement for this conversion formula with no significant proportional bias (Bland-Altman, p = 0.055) and with an intraclass correlation coefficient in the validation cohort of 0.915 (confidence interval 95% 0.786-0.966) p < 0.001. Conclusions: Calcium scoring in patients with aortic valve stenosis can be performed using contrast-enhanced computed tomography with high validity. Using a conversion factor led to an excellent agreement, thereby obviating an additional native computed tomography scan. This might contribute to a decrease in radiation exposure.

Hormone anti-müllérienne (AMH) en pédiatrie: établissement de valeurs de référence avec le dosage de l'AMH Fujirebio® Lumipulse G et comparaison avec le dosage Roche® Elecsys sur les mêmes échantillons pédiatriques

We performed a method comparison between the Fujirebio® Lumipulse G AMH assay and the Roche® Elecsys AMH assay using the same pediatric samples. We described full pediatric gender and age-specific reference ranges for AMH using the Fujirebio® AMH assay on the Lumipulse G 600 II. The study was performed on 281 plasma samples collected in tubes with lithium heparin. The samples were from patients (135 males and 146 females) aged from 3 days to 22 years collected at the University Hospital Center of Tours. The Fujirebio® Lumipulse method showed excellent correlation with Roche® Elecsys but had a significant proportional positive bias. The data were used to propose pediatric reference values adapted to the Fujirebio® method. Our study described full pediatric gender and age-related reference ranges for AMH using the Fujirebio® AMH assay on the Lumipulse G600II. The delineation between normal male and female AMH concentrations make them valuable clinical tools for the monitoring of pediatric sexual and reproductive development from early childhood through the pubertal transition into adulthood.

Measuring Cardiorespiratory Fitness without Exercise Testing: The Development and Validation of a New Tool for Spanish Adults.

Background: Cardiorespiratory fitness (CRF) is an important component of overall physical fitness and is associated with numerous health benefits, including a reduced risk of heart disease, diabetes, and obesity. However, direct measurement of CRF is time-consuming and therefore not feasible for screening purposes. Methods: A maximal treadmill exercise test with the Bruce protocol was performed to estimate VO2max in 1047 Spanish men and women aged 17 to 62 years. Weight, height, and heart rate were measured. Leisure-time physical activity (LTPA) was recorded using the Minnesota Leisure Time Physical Activity Questionnaire. A multiple linear regression model was developed to predict exercise-based VO2max. The validity of the model was examined by correlation, concordance, Bland-Altman analysis, cross-validation, and construct validity analysis. Results: There was no significant difference between VO2max obtained by the Bruce protocol (43.56 mL/kg/min) or predicted by the equation (43.59 mL/kg/min), with R2 of 0.57, and a standard error of the estimate of 7.59 mL/kg/min. Pearson's product-moment correlation and Lin's concordance correlation between measured and predicted CRF values were 0.75 and 0.72, respectively. Bland-Altman analysis revealed a significant proportional bias of non-exercise eCRF, overestimating unfit and underestimating highly fit individuals. However, 64.3% of participants were correctly classified into CRF tertile categories, with an important 69.9% in the unfit category. Conclusions: The eCRF equation was associated with several cardiovascular risk factors in the anticipated directions, indicating good construct validity. In conclusion, the non-exercise eCRF showed a reasonable validity to estimate true VO2max, and it may be a useful tool for screening CRF.

High concordance of blood glucose measurement in cats between a beta prototype glucometer device and a reference laboratory standard in a clinical setting.

The objective of this study was to evaluate the accuracy of a beta prototype version of a new portable blood glucose meter in feline patients. 60 client-owned cats. In this prospective study, 3-mL blood samples were collected from each cat and analyzed in triplicate using a beta prototype device (AlphaTRAK 3 [AT3]) and by a reference lab standard immediately after collection. Accuracy of the AT3 device was determined in accordance with the International Organization of Standardization (ISO) 15197:2013 criteria, including Bland-Altman plotting and consensus error grid analysis. A Passing-Bablok regression analysis was also performed. 96% of feline measurements fell within the ISO accuracy threshold, and 100% of measurements fell within zones A and B of the consensus error grid, meeting the ISO accuracy requirements. There was no significant bias in the data according to the Bland-Altman analysis. Within the full range of glucose concentrations (20 to 750 mg/dL) the correlation coefficient between the AT3 and the reference lab standard was 0.99. There was no significant constant or proportional bias present in the data. The AT3 device met the ISO requirements and is accurate for measurement of blood glucose concentrations in cats.

Agreement Between a Colorimetric Assay and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry for Quantifying Paracetamol Plasma Concentrations.

Special populations, like geriatric patients, experience altered paracetamol pharmacokinetics (PK), complicating pain management. More PK research is essential to optimize paracetamol (acetaminophen) dosing. Yet, the reference method ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is not readily available. Therefore, we aimed to evaluate the agreement between UPLC-MS/MS and the more accessible colorimetric Roche acetaminophen (ACETA) assay in quantifying paracetamol plasma concentrations, to facilitate PK studies and therapeutic drug monitoring for pain management. Patient data and plasma samples were obtained from a prospective study including geriatric patients admitted to the geriatric wards. ACETA and UPLC-MS/MS assays were performed in two separate laboratories. Bland-Altman plot and Passing-Bablok regression were used to assess agreement. Accuracy was evaluated using the McNemar test for a threshold value of 10mg/L. Population PK modeling was employed to bridge PK data obtained from both methods (NONMEM 7.5). A total of 242 plasma sample pairs were available from 40 geriatric patients (age range, 80-95years). Paracetamol plasma concentrations from ACETA (median 9.8 [interquartile range 6.1-14.4] mg/L) and UPLC-MS/MS (9.5 [6.2-14.8] mg/L) did not differ significantly (P > 0.05). No significant proportional nor additive bias was observed between both assay methods. The classification accuracy (at threshold 10mg/L) was 85% (P = 0.414). The conversion factor between ACETA and UPLC-MS/MS was estimated at 1.06 (relative standard error 5%), yet with a 13.4% (relative standard error 23%) interindividual variability. ACETA assay showed no systematic bias in comparison with the UPLC-MS/MS assay in determining paracetamol exposure in geriatric blood samples despite the imprecision.

Body composition assessment in 6-month-old infants: A comparison of two- and three-compartment models using data from the Baby-bod study.

An appreciation of infant body composition is helpful to understand the 'quality' of growth in early life. Air displacement plethysmography (ADP) using PEA POD and the deuterium dilution (DD) technique are commonly used body composition approaches in infants. We evaluated the comparability of body composition assessed using both techniques with two-compartment (2C) and three-compartment (3C) models in 6-month-old infants. Infant fat mass (FM) and percent fat mass (%FM) obtained from a 2C model using PEA POD (2C-PP) and a 2C model using the deuterium dilution technique (2C-DD) were compared to those derived from a 3C model, and to each other, using Bland-Altman analysis and Deming regression. Measurements were available from 68 infants (93% Caucasian, 53% male). The mean biases were not significant between any of the method comparisons. However, significant constant and proportional biases were identified in 2C-DD vs 3C and 2C-PP vs 2C-DD, but not in the 2C-PP vs 3C comparison. Furthermore, we observed significant associations between the mean differences and infants' percent total body water (%TBW). While no significant between-method mean differences were found in body composition estimates, some comparisons revealed significant constant and proportional biases and notable associations between the mean differences and %TBW were observed. Our results emphasise the importance of method choice, ensuring methodological uniformity in long-term studies, and carefully considering and regulating multiple pre-analytical variables, such as the hydration status of the participants.

IVsight as an Infusion Monitor for Patients Receiving Intravenous Therapy: An Exploratory, Unblinded, Single-Center Trial

Intravenous (IV) infusion therapy is commonly used in health care settings. However, IV therapy at home can be challenging because it relies on the patient's ability to manage multiple medications correctly, which may lead to decreased treatment adherence. We aimed to assess the usability and accuracy of the IVsight monitor in capturing IV infusion data compared to manual recording. A prospective, single-center, usability study involving patients receiving IV infusion therapy at one of the BJC's Home Infusion suites was conducted to evaluate the accuracy, performance, and acceptability of the device IVsight as a monitor for IV infusions. Of the 15 participants, the median (IQR) age was 46 years (36-55), 8 (53%) were female, and 13 (87%) were non-Hispanic white. Each participant received a median (IQR) of 4 (4-5) infusions during the study, and 68 infusions were observed overall. The intraclass correlation coefficient between the IVsight measurement and manual recording of infusion duration in seconds was excellent (ICC 0.97, 95% confidence interval 0.96-0.98). The Bland-Altman plot visually showed an acceptable limit of agreement for the 2 measurements, and the linear regression analysis revealed no significant proportional bias between the 2 methods for measuring the IV infusion time. None of the participants thought that IVsight was difficult to hold, use, clean, or store. Only one participant was concerned that the device could interfere with the IV infusion, and all participants felt comfortable with the device transmitting data to their health care providers. The IVsight infusion monitoring device showed near-perfect agreement on the recorded IV infusion duration compared with manual recording, and good acceptability among the study participants.

Evaluation of Agreement Between Sweep Visual Evoked Potential Testing and Subjective Visual Acuity.

The primary objective of this study was to evaluate the agreement of visual acuity (VA) obtained with the sweep visual evoked potential (sVEP) method with the VA obtained with the Snellen chart. The secondary objective was to examine the effect of age and gender on agreement. Best corrected VAs of subjects were recorded with the Snellen chart, and sVEP testing was performed according to the recommendations of the International Society for Clinical Electrophysiology of Vision (ISCEV). Snellen VAs and sVEP measurements were analyzed using logMAR conversion for statistical analysis. Agreement was evaluated with Bland-Altman analysis. The study included 49 subjects with a mean age of 53.5±17.3 years (range: 19-75 years) and mean Snellen VA of 0.31±0.32 logMAR (range: 1.3-0.0 logMAR). In the Bland-Altman analysis, the mean differences between the VA and sVEP measurements (VA-sVEP) were significantly different and outside the limits of agreement (p=0.035). A significant proportional bias (p=0.0007) was found in the regression analysis performed between VA-sVEP and the mean VA. According to the Bland-Altman analysis of sex subgroups, there was a significant difference between VA and sVEP measurements in female subjects (p=0.006). The difference between VA and sVEP measurement increased significantly with older age (R2: 0.306, p<0.001, β: 0.05 [0.03, 0.08]). In conclusion, sVEP measurements and VAs did not show statistical agreement. Cranial anatomy and endocrine differences of the subjects may affect their sVEP measurements. The difference between the methods varies according to VA level. Directly using sVEP results instead of VA would not be appropriate.