Capillary Whole Blood Research Articles

Detection of Islet Autoantibodies in Whole Blood by Antibody Detection by Agglutination-PCR (ADAP) Technology Is Sensitive and Suitable for General Population Screening Programs

Background. Detection of type 1 diabetes (T1D) at the preclinical stage is possible by detecting islet autoantibodies (IAs) years before the appearance of symptomatic diabetes. The Antibody Detection Israeli Research is a general population screening program searching for children with multiple IAs who are at risk of developing T1D. IAs are measured in capillary or venous whole blood (WB) samples using the novel ultrasensitive antibody detection by agglutination-PCR (ADAP) technology. Objective. To assess the accuracy and reliability of the ADAP assay in venous and capillary WB. Materials and Methods. In total, 50 children with T1D and 50 healthy controls participated in the study. Venous and capillary blood samples were drawn from participants with T1D, while only venous blood was drawn from the controls. The ADAP assay in venous and capillary blood was compared to the currently used assays in their ability to detect glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A), and insulin autoantibodies (IAAs). Results. The area under the curve using the receiver operating characteristic curves was comparable between the ADAP assay in WB and standard enzyme-linked immunosorbent assay (ELISA)/radioimmunoassay (RIA) for all three IAs GADA 0.946 (95% CI: 0.900–0.991) vs. 0.949 (0.906–0.992), P=0.873; IA-2A 0.747 (0.649–0.844) vs. 0.666 (0.587–0.744), P=0.106; IAA 1.000 (1.000–1.000) vs. 1.000 (1.000–1.000), P=1.000. The correlation between the levels of IA in venous and capillary WB using ADAP was R2 = 0.958 (P <0.01), R2 = 0.943 (P <0.01), and R2 = 0.711 (P <0.01) for GADA, IA-2A, and IAA, respectively. IA levels in venous and capillary WB using ADAP were comparable without a proportional bias in Bland–Altman’s plots of agreement, suggesting the two methods may be used interchangeably. Conclusions. The ADAP assay is reliable in detecting IA in venous and capillary WB samples with comparable performance to standard RIA and ELISA. These findings open avenues for widespread use of the ADAP assay in future general population screening programs to detect children at risk of developing T1D.

Validation Study of Novel Point-of-Care Tests for Infliximab, Adalimumab and C-Reactive Protein in Capillary Blood and Calprotectin in Faeces in an Ambulatory Inflammatory Bowel Disease Care Setting.

Background and aims: Point-of-care tests (POCT) allow instant measurement of inflammatory markers and drug concentrations. Here, we studied agreement between a novel POCT device and reference methods of measuring infliximab (IFX) and adalimumab (ADL) serum concentrations and C-reactive protein (CRP) and faecal calprotectin (FCP) concentrations of patients with inflammatory bowel disease (IBD). Methods: In this single-centre validation study, IBD patients were recruited in which IFX, ADL, CRP and/or FCP tests were required. IFX, ADL and CRP POCT were performed on capillary whole blood (CWB), obtained via finger prick. Additionally, IFX POCT was performed on serum samples. FCP POCT was performed on stool samples. Agreement between POCT and reference methods was tested using Passing-Bablok regression, intra-class correlation coefficients (ICC) and Bland-Altman plots. Results: In total, 285 patients participated. Passing-Bablok regression identified differences between the reference method and IFX CWB POCT (intercept = 1.56), IFX serum POCT (intercept = 0.71, slope = 1.10) and ADL CWB POCT (intercept = 1.44). There were also differences in the Passing-Bablok regressions of CRP (intercept = 0.81, slope = 0.78) and FCP (intercept = 51 and slope = 0.46). Bland-Altman plots demonstrated that IFX and ADL concentrations were slightly higher with the POCT and CRP and FCP were slightly lower with POCT. The ICC demonstrated almost perfect agreement with IFX CWB POCT (ICC = 0.85), IFX serum POCT (ICC = 0.96), ADL CWB POCT (ICC = 0.82) and CRP CWB POCT (ICC = 0.91) and moderate agreement with FCP POCT (ICC = 0.55). Conclusions: IFX and ADL results were slightly higher with this novel rapid and user-friendly POCT, whereas CRP and FCP results were slightly lower compared to the reference methods.

Evaluation of performance of two SARS-CoV-2 Rapid IgM-IgG combined antibody tests on capillary whole blood samples from the fingertip.

The SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) is responsible for the infectious respiratory disease called COVID-19 (COronaVIrus Disease 2019). In response to the growing COVID-19 pandemic, point-of-care (POC) tests have been developed to detect specific antibodies, IgG and IgM, to SARS-CoV-2 virus in human whole blood. We conducted a prospective observational study to evaluate the performance of two POC tests, COVID-PRESTO® and COVID-DUO®, compared to the gold standard, RT-PCR (real-time reverse transcriptase polymerase chain reaction). RT-PCR testing of SARS-Cov-2 was performed from nasopharyngeal swab specimens collected in adult patients visiting the infectious disease department at the hospital (Orléans, France). Capillary whole blood (CWB) samples from the fingertip taken at different time points after onset of the disease were tested with POC tests. The specificity and sensitivity of the rapid test kits compared to test of reference (RT-PCR) were calculated. Among 381 patients with symptoms of COVID-19 who went to the hospital for a diagnostic, 143 patients were RT-PCR negative. Results of test with POC tests were all negative for these patients, indicating a specificity of 100% for both POC tests. In the RT-PCR positive subgroup (n = 238), 133 patients were tested with COVID-PRESTO® and 129 patients were tested with COVID-DUO® (24 patients tested with both). The further the onset of symptoms was from the date of collection, the greater the sensitivity. The sensitivity of COVID-PRESTO® test ranged from 10.00% for patients having experienced their 1st symptoms from 0 to 5 days ago to 100% in patients where symptoms had occurred more than 15 days before the date of tests. For COVID-DUO® test, the sensitivity ranged from 35.71% [0-5 days] to 100% (> 15 days). COVID-PRESTO® and DUO® POC tests turned out to be very specific (none false positive) and to be sensitive enough after 15 days from onset of symptom. These easy to use IgG/IgM combined test kits are the first ones allowing a screening with CWB sample, by typing from a finger prick. These rapid tests are particularly interesting for screening in low resource settings.

Validation of hepatitis C virus RNA detection using capillary blood by finger prick (GenXpert system)-Hepatitis C fingerprick study.

To achieve the ambitious goals of the WHO to eliminate hepatitis C virus (HCV) infection as a public health threat by 2030, innovative approaches are needed to improve the uptake for screening and treatment in people who inject drugs (PWID). Important barriers to care are difficult venous access and the two-step approach in current point-of-care tests, using an HCV antibody screening test followed by a confirmatory HCV RNA test. In this study, we aimed to validate the new GenXpert instrument to diagnose HCV RNA by finger prick. This prospective study was conducted in a cohort of PWID in 6 alcohol/drug clinic sites and 1 outreach project in Belgium between January 2018 and March 2019. Plasma and capillary whole-blood samples were collected by venepuncture and finger prick, respectively. Sensitivity and specificity of the GenXpert system were compared to the gold standard Artus HCV RNA kit. Of 153 participants enrolled, 147 (96.1%) had results of both the GenXpert system and Artus HCV RNA kit available. HCV RNA was detected in 35 of 147 (23.8%) by the Artus HCV RNA kit and in 36 of 147 (24.8%) by the GenXpert. Median quantitative HCV RNA viral load on finger prick was 28700IU/mL (IQR 4070-65875) vs 1900000IU/mL (IQR 416,466-2,265,510) on plasma. The GenXpert instrument had a sensitivity of 100% (95% CI 90%-100%) and a specificity of 99.1% (95.1%-99.9%). The overall diagnostic accuracy was 99.3% (96.3%-99.9%). This study validates the excellent performance of the GenXpert instrument to assess HCV RNA in capillary whole blood by finger prick in a PWID cohort.

Population pharmacokinetic assessment of a new regimen of mefloquine used in combination treatment of uncomplicated falciparum malaria.

A fixed artesunate-mefloquine combination, comprising three daily doses of 8 mg of mefloquine/kg of body weight and 4 mg of artesunate/kg, has been developed recently. This study was designed to construct a population pharmacokinetic model describing this new dosage regimen of mefloquine given as loose tablets together with artesunate. In two randomized trials in Thailand which evaluated the efficacy, safety, and tolerability of this new regimen, the members of a subgroup of 50 patients were randomized to have capillary blood sampling before treatment and at five randomly assigned time points during the 63-day follow-up period. Mefloquine levels in capillary whole blood were assayed by liquid chromatography with UV detection. A pharmacokinetic model for mefloquine was constructed using mixed-effects modeling. A one-compartment model with first-order absorption and elimination was selected to describe the kinetic properties of mefloquine. For capillary whole-blood mefloquine, the area under the concentration curve (AUC) was 40% higher than previous estimates for patients given the equivalent conventional-dose regimen (mefloquine given as 15 mg/kg and then 10 mg/kg on the second and third days of treatment). The half-life (t1/2) of the carboxylic acid metabolite was estimated as 26 days, and the metabolite was eliminated more slowly than the parent drug (population t1/2 estimate, 10.5 days). Splitting the 25 mg/kg dose of mefloquine into three doses of 8 mg/kg each resulted in improved oral bioavailability compared to the conventional split-dose regimen results. This new regimen is well tolerated and results in an equivalent therapeutic response.

Assessment of trueness of glucose measurement instruments with different specimen matrices

Background The trueness of glucose monitors is commonly assessed using whole-blood samples and a clinical analyzer as a comparison method. In this study, the effect of specimen matrix on trueness of one clinical analyzer and one glucose monitor was compared with a gas chromatography–mass spectrometry (GC/MS) reference method, using split-sample comparison with capillary whole blood (CWB), venous whole blood (VWB), and plasma (PL). Methods CWB was analyzed by the glucose monitor and the GC/MS reference method. VWB was analyzed by the glucose monitor, clinical analyzer, and the GC/MS method. PL was analyzed by the clinical analyzer and the GC/MS reference method. Results For the glucose monitor, the bias was 0.4% and − 18.2% for CWB and VWB, respectively. The clinical analyzer had a bias of − 25.4% for VWB and − 12.0% for PL and a proportional bias was detected in both specimens. Using the clinical analyzer as a comparison method, the glucose monitor had a proportional bias of − 9.8%. Conclusion The trueness of clinical analyzers can be affected by the specimen matrix that needs to be assessed before they are used as comparison method to assess trueness of glucose monitors.

Concentration of unconjugated estriol in capillary whole blood from pregnant women.

A radio-immunological method applied to the estimation of unconjugated estriol in capillary whole blood is described. The concentration of unconjugated estriol in capillary whole blood and venous serum from 35 pregnant women was measured. Close relation was found between values in venous serum and capillary whole blood. The intra-assay variation was 4.9% for venous and 7.8% for capillary whole blood samples when analysed in duplicate. The day-to-day variability was of the same order for venous (10.0%) as for capillary (8.4%) samples. It is concluded that unconjugated estriol can be measured in small amounts (25 microliter) of capillary whole blood and that this method offers practical advantages over methods using venous serum or plasma.

HYPERGLYCÆMIA AND DIABETES MELLITUS

Recommended criteria for the diagnosis of maturity-onset diabetes mellitus based on glucose tolerance tests vary considerably; none are derived from long-term observations of the further development of different degrees of glucose intolerance. Evidence from several epidemiological investigations suggests that the risk of specific diabetic complications becomes important only in people with capillary wholeblood sugar concentrations exceeding 200 mg/dl 2 hours after a 50 g oral glucose load, who have overnight fasting blood-sugar concentrations usually exceeding 110 mg/dl. Lesser degrees of glucose intolerance may, nevertheless, indicate an additional risk of atherosclerotic arterial disease. Assessment of "borderline diabetics" should, therefore, include an evaluation of other known risk factors for arterial disease and any treatment programme should be determined in the light of these as well as by the degree of glycæmia.