Point of care assay for blood aripiprazole concentrations: development, validation and utility.

BACKGROUND: The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis. AIMS: To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole. METHOD: Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method. RESULTS: A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml). CONCLUSIONS: The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.

Empiricism in Microsampling: Utilizing a Novel Lateral Flow Device and Intrinsic Normalization to Provide Accurate and Precise Clinical Analysis from a Finger Stick.

BACKGROUND: Phlebotomy plays a key role in clinical laboratory medicine but poses certain challenges for the patient and the laboratory. Dried blood spots simplify collection and stabilize specimens effectively, but clinical reference intervals are based primarily on serum or plasma. We evaluated use of dried separated blood plasma specimens to simplify plasma sample collection via finger stick; however, this sampling technique posed substantial analytical challenges. We discuss herein our efforts to overcome these challenges and provide accurate and precise clinical measurements. METHODS: Microsamples of whole blood were collected via finger stick using a collection device employing laminar-flow separation of cellular blood and plasma fractions with subsequent desiccation. Samples were analyzed on modern autoanalyzers with FDA-approved reagent and calibration systems, as well as commercially available reagents with laboratory-developed assay parameters. Measured analyte concentrations from extracted dried plasma samples were normalized to a coextracted endogenous analyte, chloride. RESULTS: Chloride normalization reduced variability incurred through extraction and undefined plasma volume. Excellent correlation of normalized measurements from dried finger-stick samples (whole blood and plasma) versus matched venous samples facilitated developing mathematical transformations to provide concordance between specimen types. Independent end-to-end performance verification yielded mean biases <3% for the 5 analytes evaluated relative to venous drawn samples analyzed on FDA-approved measurement systems. CONCLUSION: Challenges inherent with this microsampling technique and alternate sample matrix were obviated through capabilities of modern autoanalyzers and implementation of chloride normalization. These results demonstrate that self-collected microsamples from a finger stick can give results concordant with those of venous samples.

Noninvasive Technique for Estimating Blood Glucose Levels among Diabetic Patients.

AIM: The present study was aimed to assess the fasting and postprandial gingival crevicular blood (GCB) glucose and finger stick blood glucose measurements using a glucometer. MATERIALS AND METHODS: A total of 30 subjects with periodontitis and positive bleeding on probing were considered. Subjects were instructed to report to the department after overnight fasting. Gingival crevicular blood samples were collected from anterior region showing bleeding on probing followed by finger stick blood sample collection. Then, the patients were instructed to take 75 gm of glucose and after 2 hours blood samples from two sites were collected similarly. Results were analyzed using unpaired t test and Pearson's correlation. RESULTS: Mean glucose levels form GCB and finger stick blood did not differ either during fasting or postprandial (p > 0.05). Significant correlation was found between GCB glucose levels and capillary finger stick blood (CFB) glucose levels during fasting (r = 0.946, p < 0.001) and postprandial (r=0.930, p < 0.001) blood estimation. CONCLUSION: Periodontal probing can be considered as an alternate noninvasive method of blood glucose estimation for screening of diabetes mellitus (DM). The technique described is safe, easy to perform, and helps to increase the frequency of diabetes screening in dental office. CLINICAL SIGNIFICANCE: The GCB from probing can be a good source of blood for estimating blood glucose levels and screening for diabetes using portable glucose monitors. Also, it will be a simple and relatively inexpensive in office screening procedure for any patient suspected to have diabetes.

A Preliminary Analysis of Thyrotropin Measurement from Finger Stick Dried Blood Spot with an Automated High-Throughput Immunoassay Analyzer.

Background: Hyper- and hypothyroidism are prevalent in Western countries and often go unnoticed for long periods. Thyrotropin (TSH) as a biomarker of thyroid dysfunction is regularly measured in venous plasma/serum. In newborn screening for congenital hypothyroidism, TSH is measured from dried blood spots (DBSs). DBS enables minimally invasive (at-home) sampling of a small blood volume that can be sent to diagnostic laboratories by regular mail. Methods: In this study, we included 109 patients who presented to the outpatient clinic of the University Medical Center Utrecht. Capillary finger stick was used to spot blood on a filter paper card and was dried. After extraction of TSH from DBS, method comparison with venous TSH was performed on an automated high-throughput immunoassay analyzer. Additional validation steps regarding stability, effect of hematocrit (Hct), precision, and limits of blank and quantitation were conducted according to corresponding Clinical and Laboratory Standards Institute evaluation protocol. Results: Method comparison of TSH from venous plasma versus finger stick DBSs showed an R2 [95% confidence interval] = 0.988 [0.986-0.990]. This enabled correct diagnosis of hypothyrotropinemia and hypothyroidism in 12 of 14 and 6 of 7 cases, respectively, with no false positives. Furthermore, TSH from DBS was stable for at least 4 days at temperatures between -20°C and +30°C, and the maximum decrease of eluate TSH was 1.13% for 1% increase in Hct. Conclusions: TSH from DBS may be accurately measured on an automated high-throughput immunoassay analyzer and could be used to diagnose hypothyroidism and, for the first time, hypothyrotropinemia. This method, when confirmed in larger field studies, may enable individuals to engage in (at-home) sampling of blood on DBSs for telediagnostics, screening programs, patient follow-up, and medication management.

Using Capillary Whole Blood to Quantitatively Measure Ferritin: A Validation Trial of a Point-of-Care System.

Iron deficiency is a public health problem with devastating health, developmental and behavioral effects which often exacerbated due to affordability and access to screening and diagnosis. Using IronScan™ a portable, point-of-care diagnostic system capable of quantitatively measuring ferritin in blood, we validated IronScan™ ferritin measurements using whole blood and serum with a lab-based, regulator-approved analytical device for measuring ferritin in venous serum. Capillary (finger stick) and venous whole blood samples were obtained from 44 male and female volunteers. Venous serum (vSer) ferritin concentrations were measured on Immulite 2000 Xpi (gold standard). Capillary whole blood (cWB), venous whole blood (vWB), and vSer ferritin levels were measured by IronScan™. cWB ferritin concentrations from IronScan™ were significantly correlated (R2 = 0.86) with vSer measured with the FDA-approved Immulite system. The results from the multiple regression analysis indicate that 10% of the variability was due to the method of blood collection (venous vs. capillary) and 6% was due to the form of blood analysis (whole blood vs. serum). The sensitivity of diagnosing iron deficiency using the WHO cutoff of <30 ng/mL is 90%, with a specificity of 96%. In conclusion, IronScan™ is a rapid viable option for measuring ferritin as a point-of-care system.

Using a fingerstick test for haematological monitoring in patients treated with clozapine.

BACKGROUND: Treatment with clozapine requires regular blood monitoring in order to minimise the risk of agranulocytosis. The demands on patients and clinicians associated with monitoring may be reduced by using point-of-care, as opposed to lab-based assessments. We assessed the utility of a device that can measure white blood cell (WBC) and neutrophil counts by capillary fingerstick blood. METHOD: The performance of a small, portable device (HemoCue® WBC DIFF System) was compared with that of a widely used laboratory analyser (ADVIA® 2120i) for measuring WBC and neutrophil counts. Patients with schizophrenia who were being treated with clozapine (n = 201) provided a fingerstick capillary sample and a venous sample for the respective assays. RESULTS: WBC counts and neutrophil counts from venous blood as determined by ADVIA 2120i, ranged from 3.0 × 109/l to 19.5 × 109/l, and 1.2 × 109/l to 15.9 × 109/l, respectively. There was a strong correlation between the results from venous and the capillary sample methods (WBC: R = 0.89, neutrophil: R = 0.92). By Passing-Bablok regression analysis, the slope of the association between ADVIA® 2120i and HemoCue WBC DIFF for WBC was 1.0 [95% confidence interval (CI) 0.944-1.086], with intercept at -0.9 (95% CI -1.43 to -0.45). For neutrophils, the slope was 0.870 (95% CI 0.817-0.923), with intercept at -0.19 (95% CI -0.43 to 0.02). Overall, mean biases of -0.95 × 109/l for WBC, and -0.91 × 109/l for neutrophils were observed for the capillary blood method compared with the venous blood method. Below the clinical cutoff intervals for clozapine monitoring WBC (<3.5 × 109/l) and neutrophils (<1.5 × 109/l) these biases were -1.1 × 109/l for WBC, and -0.25 × 109/l for neutrophils. CONCLUSION: Results from the capillary blood HemoCue WBC DIFF analyser compared well with the venous blood ADVIA 2120i analyser for determining WBC and neutrophil counts. There was a slight overall bias, with the capillary method reporting lower values for both measures. Fingerstick point-of-care analysis is suitable for monitoring blood counts in patients on clozapine, although confirmatory standard venous testing is recommended for test results falling below accepted thresholds.

Point-of-care measurement of clozapine concentration using a finger-stick blood sample.

BACKGROUND: The use of clozapine demands regular monitoring of clozapine plasma concentrations and of white blood cell parameters. The delay between sending blood samples for analysis and receiving the results hinders clinical care. Point-of-care testing (POCT) can provide drug assay results within a few minutes. AIM: This study aimed to investigate the utility of a novel point-of-care device that can measure clozapine concentrations using capillary blood samples collected via a finger stick. METHOD: During a five-week period starting in June 2019 eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Samples were analysed by the novel point-of-care device and by the standard laboratory method. Capillary blood samples were tested by the MyCare™ Insite POCT analyser, and a quantitative measurement of clozapine concentration was provided within six minutes. RESULTS: A total of 309 patients agreed to measurements by the two methods. Analysis revealed clozapine concentrations in venous blood as determined by the laboratory method ranged from 20 to 1310 ng/mL and by POCT from 7 to 1425 ng/mL. There was a strong positive correlation (R = 0.89) between the results from the venous and the capillary sample methods. The slope of the association between standard assay and MyCare™ Insite was 1.0 with an intercept of -21 ng/mL, indicating minimal bias. CONCLUSION: Clozapine concentrations can be accurately measured at the point of care using capillary blood samples collected via a finger stick. This approach may be more acceptable than venous sampling to patients and, with almost instant results available, more useful to clinicians.

Use of a capillary specimen in the laboratory to verify a point-of-care international normalized ratio: Avoidance of a venipuncture in a pediatric setting.

INTRODUCTION: Point-of-care (POC) international normalized ratio (INR) values above an institutional cutoff are confirmed in the laboratory using a gold standard venous specimen. This can be problematic in a pediatric setting. METHOD: In this study, 449 consecutive POC INR results were compared to an INR performed in the laboratory on a capillary citrate specimen collected from the same finger-stick. The results were statistically analyzed. RESULTS: The mean INR values from the CoaguChek XS and laboratory were 2.85 ± 1.19 and 2.63 ± 1.11, respectively. There was a good correlation between the methods with r = 0.97. Bland-Altman analysis indicated a bias of 0.22 favoring the CoaguChek XS, with 95% limits of agreement -0.29 to 0.72. Passing and Bablok method comparison resulted in a slope of 0.91 (y = 0.91x + 0.02). An INR of ≤0.5 was found between the methods in 89% of cases and 84% agreement was noted (κ = 0.69). CONCLUSION: Comparing the capillary INR laboratory results to studies involving a venous specimen, the capillary specimen performed with equivalence. Thus, a capillary citrate specimen can be collected from the same finger-stick used to perform the POC INR for confirmation in the laboratory. This avoids the trauma of a venous collection in such a situation.

Claros System: A Rapid Microfluidics-Based Point-of-Care System for Quantitative Prostate Specific Antigen Analysis from Finger-Stick Blood.

INTRODUCTION: Determination of circulating prostate specific antigen (PSA) is commonly used in the diagnosis and treatment monitoring of prostate cancer [1]. Presently, PSA testing is performed in centralized laboratories, which is associated with prolonged time between venipuncture and the PSA value being available. In this prospective study, we present a new and rapid test system for the quantitative determination of PSA levels from finger-stick blood. METHODS: The Claros1® analyzer is a rapid microfluidics-based point-of-care system for quantitative PSA analysis from 10-µl finger-stick blood that requires only 10 min for testing. Total PSA concentrations by the Claros system in 100 consecutive asymptomatic men (median age 57 years, range 44-81 years) were compared with two commercially available, commonly used PSA assays (Abbott and Elecsys by Roche) performed by a reference laboratory. RESULTS: Eighty-six percent of finger-stick blood-borne probes from 100 men were evaluable for PSA testing by the Claros1® analyzer system. In 13/14 cases the expiry date of the microfluid cassettes of the Claros system was exceeded and one blood puncture was performed inadequately. The correlations between the Claros results and OPKO-Abbott and OPKO-Roche assay results were high, with R2 values of 0.982 and 0.985, respectively. The R2 value for the Roche-Abbott correlation was 0.991 with a slope value of 1.160. Prostate cancer was diagnosed in seven cases, with a median PSA of 1.8 ng/ml in the Claros group compared to 1.75 ng/ml and 2.1 ng/ml in the Abbott and Roche groups, respectively. CONCLUSION: The Claros1® PSA assay combines the advantages of rapid, accurate detection with a low required sample volume, allowing the analysis to be performed using finger-stick blood. Provided that further analysis proves the reproducibility of the test, it may help to reduce the number of office visits, thus decreasing costs to the health care system.

Estimation of gingival crevicular blood glucose level for the screening of diabetes mellitus: A simple yet reliable method.

AIM: This study was designed to assess the reliability of blood glucose level estimation in gingival crevicular blood(GCB) for screening diabetes mellitus. MATERIALS AND METHOD: 70 patients were included in study. A randomized, double-blind clinical trial was performed. Among these, 39 patients were diabetic (including 4 patients who were diagnosed during the study) and rest 31 patients were non-diabetic. GCB obtained during routine periodontal examination was analyzed by glucometer to know blood glucose level. The same patient underwent for finger stick blood (FSB) glucose level estimation with glucometer and venous blood (VB) glucose level with standardized laboratory method as per American Diabetes Association Guidelines.1 All the three blood glucose levels were compared. Periodontal parameters were also recorded including gingival index (GI) and probing pocket depth (PPD). RESULTS: A strong positive correlation (r) was observed between glucose levels of GCB with FSB and VB with the values of 0.986 and 0.972 in diabetic group and 0.820 and 0.721 in non-diabetic group. As well, the mean values of GI and PPD were more in diabetic group than non-diabetic group with the statistically significant difference (p < 0.005). CONCLUSION: GCB can be reliably used to measure the blood glucose level as the values were closest to glucose levels estimated by VB. The technique is safe, easy to perform and non-invasive to the patient and can increase the frequency of diagnosing diabetes during routine periodontal therapy.

The use of finger-stick blood to assess lactate in critically ill surgical patients.

BACKGROUND: Using finger-stick capillary blood to assess lactate from the microcirculation may have utility in treating critically ill patients. Our goals were to determine how finger-stick capillary lactate correlates with arterial lactate levels in patients from the surgical intensive care unit, and to compare how capillary and arterial lactate trend over time in patients undergoing resuscitation for shock. METHODS: Capillary whole blood specimens were obtained from finger-sticks using a lancet, and assessed for lactate via a handheld point-of-care device as part of an "investigational use only" study. Comparison was made to arterial blood specimens that were assessed for lactate by standard laboratory reference methods. RESULTS: 40 patients (mean age 68, mean APACHEII 18, vasopressor use 62%) were included. The correlation between capillary and arterial lactate levels was 0.94 (p < 0.001). Capillary lactate measured slightly higher on average than paired arterial values, with a mean difference 0.99 mmol/L. In patients being resuscitated for septic and hemorrhagic shock, capillary and arterial lactate trended closely over time: rising, peaking, and falling in tandem. Clearance of capillary and arterial lactate mirrored clinical improvement, normalizing in all patients except two that expired. CONCLUSION: Finger-stick capillary lactate both correlates and trends closely with arterial lactate in critically ill surgical patients, undergoing resuscitation for shock.

Gingival crevicular blood: As a non-invasive screening tool for diabetes mellitus in dental clinics.

BACKGROUND: A high number of patients with periodontitis may have undiagnosed diabetes. Self-monitoring devices provide a simple method for rapid monitoring of the glucose level in the blood by utilizing a blood sample from the finger, but this method requires a needle puncture to obtain blood. It is possible that gingival crevicular blood (GCB) from routine periodontal probing may be a source of blood for glucose measurements. AIM: To establish whether GCB can be used as a non-invasive diagnostic aid in screening for diabetes mellitus during routine periodontal examination. MATERIALS AND METHODS: The study involved 50 diabetics and 50 non-diabetics, with an age range of 26-66 years. Both diabetic and non-diabetic patients had moderate to severe gingivitis with at least one tooth in the maxillary anterior region showing bleeding upon probing. The Gingival Index and Oral Hygiene Index-Simplified were recorded. Blood oozing from the gingival sulcus/pocket following periodontal pocket probing was collected using a capillary tube and transferred to the test stick of a glucose self-monitoring device (Accu-Chek, Roche Diagnostic, Germany) in patients with comparable gingival and oral hygiene status. This value was compared with the peripheral fingerstick blood glucose (PFBG) value, which was obtained by pricking the finger tip at the same visit. Statistical analysis was performed using Pearson's correlation coefficient. RESULT: There was no statistically significant difference between the gingival crevicular blood glucose (GCBG) values and the PFBG values in both the diabetic (P = 0.129, NS) and the non-diabetic (P = 0.503, NS) groups. Karl Pearson's product-moment correlation coefficient was calculated, which showed a positive correlation between the two measurements in the diabetic (r = 0.943) as well as the non-diabetic (r = 0.926) groups. CONCLUSION: The results suggest that GCB can be used as a non-invasive diagnostic aid in screening for diabetes mellitus during routine periodontal examination.