Finger-prick Samples Research Articles

Validating the Use of Continuous Glucose Monitors With Nondiabetic Recreational Runners.

Continuous glucose monitors (CGMs) are becoming increasingly popular among endurance athletes despite unconfirmed accuracy. We assessed the concurrent validity of the FreeStyle Libre 2 worn on 2 different sites at rest, during steady-state running, and postprandial. Thirteen nondiabetic, well-trained recreational runners (age = 40 [8]y, maximal aerobic oxygen consumption = 46.1 [6.4]mL·kg-1·min-1) wore a CGM on the upper arm and chest while treadmill running for 30, 60, and 90minutes at intensities corresponding to 50%, 60%, and 70% of maximal aerobic oxygen consumption, respectively. Glucose was measured by manually scanning CGMs and obtaining a finger-prick capillary blood glucose sample. Mean absolute relative difference, time in range, and continuous glucose Clarke error grid analysis were used to compare paired CGM and blood glucose readings. Across all intensities of steady-state running, we found a mean absolute relative difference of 13.8 (10.9) for the arm and 11.4 (9.0) for the chest. The coefficient of variation exceeded 70%. Approximately 47% of arm and 50% of chest paired glucose measurements had an absolute difference ≤10%. Continuous glucose Clarke error grid analysis indicated 99.8% (arm) and 99.6% (chest) CGM data fell in clinically acceptable zones A and B. Time-in-range analysis showed reduced accuracy at lower glucose levels. However, CGMs accurately detected trends in mean glucose readings over time. CGMs are not valid for point glucose monitoring but appear to be valid for monitoring glucose trends during steady-state exercise. Accuracy is similar for arm and chest. Further research is needed to determine whether CGMs can detect important events such as hypoglycemia during exercise.

A-346 Evaluating 14-3-3η Detection in Finger Prick Blood Using Lateral Flow Technology: Advancing Clinical Laboratory Diagnostics

Abstract Background The protein 14-3-3η is a critical biomarker in the diagnosis and monitoring of autoimmune rheumatologic disorders, and its early detection is pivotal for patient outcomes. Previous research has established the significance of 14-3-3η as a biomarker, particularly in inflammatory polyarthritis, as well as patients’ and physicians’ interest in near-patient testing. While 14-3-3η is traditionally measured in serum via ELISA, this study explores the innovative use of lateral flow technology (LFT) for its detection in finger prick blood, addressing the urgent need for near-patient testing.This research aims to evaluate the technical and clinical performance of 14-3-3η measurement using LFT in comparison to standard ELISA methods, with an emphasis on its detectability in finger prick blood. Methods This study included two phases of testing involving patient serum and spiked whole blood. In the serum phase, 53 samples (19 NEG, ≤0.19 ng/mL, and 34 POS, 0.27 to 28 ng/mL 14-3-3η) were tested using LFT. LFT results were compared to JOINTstat® ELISA measurements for concordance. For whole blood, recombinant 14-3-3η and ELISA-positive serum samples were spiked into whole blood at increasing concentrations (0.4 to 3.2 ng/mL) and tested with LFT. Concordance criteria included visual inspection of test and control lines, with results captured and analyzed using a reference key card. The study was extended to assess 14-3-3η levels in consented patients with 22 matched finger prick and venous serum samples​​. Results In serum testing, LFT demonstrated 100% positivity in detecting 14-3-3η for POS samples. Among NEG samples, 85% tested negative, with 15% positive, indicating a strong concordance between LFT and ELISA. The LFT's ability to semi-quantitatively measure 14-3-3η was confirmed by a significant Kruskal-Wallis test (p<0.0001) across four intensity groups. In whole blood testing, LFT correctly identified all samples spiked at concentrations ≥0.5 ng/mL. The Spearman correlation showed a strong and significant association (r=0.96 to 0.98, p=0.001) between LFT test line intensity and spiked 14-3-3η levels. Finally, the equivalence testing for finger prick and venous serum samples affirmed the LFT’s reliability, with a strong correlation (p<0.0001), underscoring its potential for near-patient testing​​. Conclusions The study validates LFT as a reliable and semi-quantitative method for detecting 14-3-3η in finger prick blood, demonstrating strong concordance with traditional ELISA measurements. The findings support the feasibility of LFT in near-patient testing for early detection, prognosis, and monitoring of autoimmune diseases, paving the way for enhanced patient accessibility. Future research will focus on integrating this technology into routine clinical care and examining its impact on patient management and outcomes.

Clinical validation of two volumetric absorptive microsampling devices to support home-based therapeutic drug monitoring of immunosuppression.

Dried blood volumetric absorptive microsamples (VAMS) may facilitate home-based sampling to enhance therapeutic drug monitoring after transplantation. This study aimed to clinically validate a liquid chromatography-tandem mass spectrometry assay using 2 VAMS devices with different sampling locations (Tasso-M20 for the upper arm and Mitra for the finger). Patient preferences were also evaluated. Clinical validation was performed for tacrolimus and mycophenolic acid by comparison of paired VAMS and venipuncture samples using Passing-Bablok regression and Bland-Altman analysis. Conversion of mycophenolic acid VAMS to serum concentrations was evaluated using haematocrit-dependent formulas and fixed correction factors defined a priori. Patients' perspectives, including useability, acceptability and feasibility, were also investigated using established questionnaires. Paired samples (n =50) were collected from 25 kidney transplant recipients. Differences for tacrolimus whole-blood concentration were within ±20% for 86 and 88% of samples from the upper arm and fingerstick, respectively. Using correction factors of 1.3 for the upper-arm and 1.47 for finger-prick samples, 84 and 76% of the paired samples, respectively, were within ±20% for mycophenolic acid serum concentration. Patient experience surveys demonstrated limited pain and acceptable useability of the upper-arm device. Tacrolimus and mycophenolic acid can be measured using 2 common VAMS devices with similar analytical performance. Patients are supportive of home-based monitoring with a preference for the Tasso-M20 device.

The effect of exercise on gastrointestinal symptoms and body composition at different phases of the menstrual cycle

Women commonly experience bloating, stomach cramps, water retention, and weight gain at the beginning of their menstrual cycle, which cause fluctuations in body composition through extracellular changes, this may affect osmotic pressure, leading to gastrointestinal (GI) symptoms. The aim of this study was to investigate the effect of the menstrual cycle phase on extracellular changes and GI symptoms in females in response to exercise. Seven healthy premenopausal female recreational athletes (maximal O2 consumption: 50 ± 5.8 ml·kg-1) performed two running trials in an experimental crossover design during two distinct phases of the menstrual cycle, early follicular phase (EFP) and the mid-luteal phase (MLP). Each trial consisted of 120 min of running, 60 min at 110% lactate threshold and 60 min at 90%. Determination of cycle was calculated from calendar-based counting and urinary ovulation detection kits. The EFP was determined by self-reporting onset of menses. The day before each trial, participants followed a low FODMAP diet and completed a gastrointestinal symptom rating scale questionnaire. On the morning of the trial, a standard breakfast was consumed, upon arrival at the laboratory, body composition was recorded. Each hour, finger prick samples were taken to measure lactate and ensure performance did not exceed maximum, every 15 minutes, a visual analog scale (VAS) of subjective ratings between 0-10 cm of gut comfort was taken. Data was analysed using mean and standard deviation (subsequent statistical analysis will be conducted if an n = 10 is reached prior to the conference). During exercise, participants experienced a higher prevalence of GI issues throughout the EFP compared with the MLP. The most common complaints reported from the VAS were nausea; EFP 1 ± 1 cm, MLP 0 ± 0 cm. Flatulence; EFP 4 ± 3 cm, MLP 1 ± 1 cm, and stomach cramps; EFP 3 ± 2 cm, MLP 1 ± 1 cm. Total body weight (TBW) differences were noted between the EFP and MLP. TBW EFP pre-exercise was higher than MLP pre-exercise phase EFP pre-exercise: 38.7 ± 2.8 L compared to MLP pre-exercise at 35.8 ±5.5 L. Similar differences were demonstrated with extra cellular water pre-exercise EFP; 16.1 ± 1.1 L MLP; 15.2 ±1.0 L. During the EFP fluid retention is known to be higher than the MLP, and results are as expected. While the data suggests a seemingly minimal variation in Gl symptoms, individually, there appears to be a higher level of difference. More gastrointestinal symptoms were reported during exercise, which is consistent with the findings. There is a slight difference in GI symptoms between the EFP and MLP at this stage, indicating a slight shift in total body water.

Quantification of neurofilament light and glial fibrillary acidic protein in finger-prick blood.

An accurate diagnosis of neurodegenerative disease and traumatic brain injury is important for prognostication and treatment. Neurofilament light and glial fibrillary acidic protein (GFAP) are leading biomarkers for neurodegeneration and glial activation that are detectable in blood. Yet, current recommendations require rapid centrifugation and ultra-low temperature storage post-venepuncture. Here, we investigated if these markers can be accurately measured in finger-prick blood using dried plasma spot cards. Fifty patients (46 with dementia; 4 with traumatic brain injury) and 19 healthy volunteers underwent finger-prick and venous sampling using dried plasma spot cards and aligned plasma sampling. Neurofilament light and GFAP were quantified using a Single molecule array assay and correlations between plasma and dried plasma spot cards assessed. Biomarker concentrations in plasma and finger-prick dried plasma spot samples were significantly positively correlated (neurofilament light ρ = 0.57; GFAP ρ = 0.58, P < 0.001). Finger-prick neurofilament light and GFAP were significantly elevated after acute traumatic brain injury with non-significant group-level increases in dementia (91% having Alzheimer's disease dementia). In conclusion, we present preliminary evidence that quantifying GFAP and neurofilament light using finger-prick blood collection is viable, with samples stored at room temperature using dried plasma spot cards. This has potential to expand and promote equitable testing access, including in settings where trained personnel are unavailable to perform venepuncture.

Performance analysis of point-of-care testing haemoglobin concentration methods with automated haematology analyser amongst blood donors

Abstract Background: In terms of rapidness, testing methodology and sensitivity, point-of-care (POC) testing devices provide quality in haemoglobin (Hb) check for safe donation of blood. Methods: This was a prospective observational study in a tertiary care centre. Capillary finger-prick samples obtained from 100 blood donors were analysed prior to donation using reagent-free cuvettes (DiaSpect Tm), digital haemoglobinometer (True Hb) and Hb photometer (HemoCue 301). Venous samples were drawn for analysis on haematology analyser. Donors were accepted based on copper sulphate method acceptance criteria. The performance of the devices was evaluated considering automated haematology analyser (Sysmex XN 1000) as the gold standard. Results: The mean Hb value using Sysmex XN 1000, HemoCue 301, DiaSpect Tm and True Hb were 14.8 ± 1.1 g/dL, 15.4 ± 1.8 g/dL, 15.3 ± 1.8 g/dL and 18.6 ± 2.8 g/dL, respectively. The sensitivity of True Hb, DiaSpect Tm, HemoCue 301 and copper sulphate method were 96.8%, 96.8%, 3.7% and 98.9%, respectively. DiaSpect Tm had a specificity of 60% whereas specificity of True Hb and copper sulphate method were 20% each. True Hb, HemoCue 301, DiaSpect Tm and copper sulphate had a positive predictive value of 95.8%, 94.7%, 97.9% and 95.9% and accuracy of 93%, 89%, 95% and 95%, respectively. The mean turnaround time was 1 sec for DiaSpect Tm whereas 35.3 sec and 2.6 sec for True Hb and HemoCue 301, respectively. The copper sulphate test provided the highest rate of donor’s acceptance, despite unacceptable Hb levels. Conclusions: DiaSpect Tm has the advantage of rapid turnaround time, high specificity and accuracy when compared to gold standard method.

Stability of inflammation markers in human blood collected using volumetric absorptive microsampling (VAMS) under typical laboratory storage temperatures

Dried blood spots (DBS) collected on filter paper such as Guthrie cards are stored for years at room temperature. The assumption is that once dried, the samples remain stable and quantifiable indefinitely since the metabolites these were initially designed to measure, are known for their extended stability. The concentration of other blood proteins such as cytokines, however, are known to vary with storage even in liquid samples stored at −80 °C for extended periods of time. We sought to determine if cytokines are stable for up to 5 months when stored as a dried blood sample using volumetric absorptive microsampling (VAMS) devices.To test this, blood was collected from 4 healthy participants, spiked with recombinant cytokines, and collected into 30 µL VAMS devices. These prepared VAMS devices were stored at room temperature, 4 °C, or −20 °C for up to 5 months and matching VAMS liquid extracts were stored at −80 °C for the same period of time. At each timepoint, the samples were extracted from the VAMS devices and the extracts were analysed by Luminex® for quantification of up to 31 cytokines. These methods were also tested in a remote clinical study over a period of up to 8 months.Cytokine analysis revealed that room temperature, the current standard for DBS and VAMS storage, performed the poorest out of all storage temperatures with significant losses in 13/21 analytes compared to 4 °C at 5 months. Storage at 4 °C or colder performed well for the majority of analytes tested, however out of those, the optimal storage temperature differed for each analyte. There were a small number of analytes that performed poorly regardless of storage conditions and for fractalkine, this was found to be caused by inefficient recovery during extraction. Cytokine concentrations from finger-prick samples were also found to be much more variable that those in venous blood samples.Our results highlight the need to understand the stability of analytes of interest before committing to longitudinal collection and storage of samples in VAMS devices. These data give confidence that storage at 4 °C or colder was beneficial for cytokine stability. Wherein 25/31 cytokines were quantifiably stable at −20 °C when stored for 3 months and 17/21 were quantifiably stable after 5 months when stored at 4 °C.

Clinical performance of volumetric finger-prick sampling for the monitoring of tacrolimus, creatinine and haemoglobin in kidney transplant recipients.

Finger-prick sampling has emerged as an attractive tool for therapeutic drug monitoring and associated diagnostics. We aimed to validate the clinical performance of using two volumetric devices (Capitainer® qDBS and Mitra®) for monitoring tacrolimus, creatinine and haemoglobin in kidney transplant (KTx) recipients. Secondarily, we evaluated potential differences between finger-prick sampling performed by healthcare professionals vs. self-sampling, and differences between the two devices. We compared finger-prick and venous sampling in three settings: microsampling performed by healthcare personnel, self-sampling under supervision, unsupervised self-sampling. The finger-prick samples were analysed with adapted methods and results compared to routine method analysis of the venous blood samples. Twenty-five KTx recipients completed the main study and 12 KTx recipients completed a post hoc validation study. For tacrolimus measurements and predicted area under the curve, the proportions within ±20% difference were 79%-96% for Capitainer and 77%-95% for Mitra. For creatinine and haemoglobin, the proportions within ±15% were 92%-100% and 93%-100% for Capitainer and 79%-96% and 67%-92% for Mitra, respectively. Comparing sampling situations, the success rate was consistent for Capitainer (92%-96%), whereas Mitra showed 72%-88% and 52%-72% success rates with samples collected by healthcare personnel and the patients themselves. Capitainer and Mitra are technically feasible for measuring tacrolimus, creatinine and haemoglobin. In the context of self-sampling, Capitainer maintained consistent sampling success and analytical quality. Implementing volumetric finger-prick self-sampling for the monitoring of tacrolimus, creatinine and haemoglobin may simplify and improve the follow-up of KTx recipients.

Application of Shear Horizontal Surface Acoustic Wave (SH-SAW) Immunosensor in Point-of-Care Diagnosis.

Point-of-care testing (POCT), also known as on-site or near-patient testing, has been exploding in the last 20 years. A favorable POCT device requires minimal sample handling (e.g., finger-prick samples, but plasma for analysis), minimal sample volume (e.g., one drop of blood), and very fast results. Shear horizontal surface acoustic wave (SH-SAW) biosensors have attracted a lot of attention as one of the effective solutions to complete whole blood measurements in less than 3 min, while providing a low-cost and small-sized device. This review provides an overview of the SH-SAW biosensor system that has been successfully commercialized for medical use. Three unique features of the system are a disposable test cartridge with an SH-SAW sensor chip, a mass-produced bio-coating, and a palm-sized reader. This paper first discusses the characteristics and performance of the SH-SAW sensor system. Subsequently, the method of cross-linking biomaterials and the analysis of SH-SAW real-time signals are investigated, and the detection range and detection limit are presented.

Utilizing quantitative dried blood spot analysis to objectively assess adherence to cardiovascular pharmacotherapy among patients at Kenyatta National Hospital, Nairobi, Kenya.

The burden of cardiovascular disease (CVD) is rising in Kenya and non-adherence to cardiovascular pharmacotherapy is a growing global public health issue that leads to treatment failure, an increased risk of cardiac events and poor clinical outcomes. This study assessed adherence to selected cardiovascular therapy medications among CVD patients attending outpatient clinics at Kenyatta National Hospital, Kenya by determining drug concentration(s) in patient dried blood spot (DBS) samples. Patients who had been taking one or more of the five commonly prescribed CVD medications (amlodipine, atenolol, atorvastatin, losartan, and valsartan) for at least six months were enrolled. Each patient completed a short questionnaire about their medication history and then provided a finger-prick blood spot sample from which drug concentrations were determined by liquid chromatography-high resolution mass spectrometry analysis. Two hundred and thirty-nine patients (62.3% female) participated in the study. The median number of medications used by patients was 2 (IQR 75%-25% is 3-1). Less than half (117; 49.0%) of patients were adherent to their prescribed CVD pharmacotherapy. Binary regression analysis revealed a significant correlation between non-adherence and the number of medications in the treatment regimen (Odds Ratio (OR) 1.583; 95%CI: 0.949-2.639; P-value = 0.039) and that gender was not an independent predictor of medication adherence (OR 1.233; 95%CI: 0.730-2.083; P-value = 0.216). Valuable information about adherence to each medication in the patient's treatment regimen was obtained using quantitative DBS analysis showing that adherence to CVD medications was not uniform. DBS sampling, due its minimally invasive nature, convenience and ease of transport is a useful alternative matrix to monitor adherence to pharmacotherapies objectively, when combined with hyphenated mass spectrometry analytical techniques. This information can provide physicians with an evidence-based novel approach towards personalization and optimization of CVD pharmacotherapy and implementing interventions in the Kenyan population, thereby improving clinical outcomes.

Liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of immunosuppressants and creatinine from a single dried blood spot using the Capitainer® qDBS device

In recent years, a lot of attention has been given to a more patient-centric therapeutic drug monitoring (TDM) of immunosuppressant drugs (tacrolimus, sirolimus, everolimus and cyclosporin A) by the use of microsampling techniques. By adopting Dried Blood Spots (DBS) after a finger prick, instead of conventional venous blood draws, follow-up can (partially) be established from patients’ homes. Despite the many advantages of DBS, one of the major disadvantages associated with this technique is the well described hematocrit (hct) effect. In order to overcome the hct area bias, different strategies have been proposed, amongst which the use of dried blood sampling techniques based on the volumetric collection of blood.The aim of this study was to evaluate the use of the Capitainer® qDBS (quantitative Dried Blood Spot) device for the combined TDM of four immunosuppressants and creatinine from a single qDBS. The set-up of an adequate sample preparation allowing both immunosuppressants and creatinine quantification was one of the key challenges in the method development due to device-specific interferences. Liquid chromatography tandem-mass spectrometry methods for the quantification of tacrolimus, sirolimus, everolimus, cyclosporin A and creatinine from qDBS (10 μL) were developed and validated based on international guidelines, also taking into account DBS-specific parameters. The methods proved to be accurate and reproducible, with absolute biases below 10% and within-run CVs (%) below 8% over a calibration range from 1 to 50 ng/mL for tacrolimus, sirolimus and everolimus, 20–1500 ng/mL for cyclosporin A, and 15–700 μmol/L for creatinine. Reproducible (CV < 15%) IS-compensated relative recovery values were obtained, showing no hematocrit-dependence (compared to a hct of 0.37), except for cyclosporin A at higher hct values. Application on venous blood left-over patient samples showed good agreement between the results of Capitainer® qDBS and whole blood with 98% (47/48), 93% (41/44), 89% (41/46), 88% (38/43) and 89% (116/131) of the samples lying within 20% of the whole blood result for tacrolimus, sirolimus, everolimus, cyclosporin A and plasma/serum for creatinine, respectively. For creatinine a blood/plasma ratio of 0.85 was found and used to convert qDBS results to plasma/serum results. As a next step, capillary finger prick samples will need to demonstrate the clinical applicability of the method in a real life setting.

Optical Spectrophotometry as a Promising Method for Quantification and Stage Differentiation of Plasmodium falciparum Parasites.

Malaria is one of the most life-threatening infectious diseases worldwide, claiming half a million lives yearly. Prompt and accurate diagnosis is crucial for disease control and elimination. Currently used diagnostic methods require blood sampling and fail to detect low-level infections. At the symptomatic stage of infection, the parasites feed on red blood cells' (RBCs) hemoglobin, forming inert crystals, the hemozoin, in the process. Thus, along with parasite maturation inside the RBCs, the hemoglobin and hemozoin proportion is inversely related, and they generate specific optical spectra, according to their concentration. Herein, to address the issues of finger prick sampling and the lack of sensitivity of the parasitological test, we explored the optical features of Plasmodium falciparum-infected RBCs through absorbance and reflectance spectrophotometric characterization, aiming for their detection. This is the first work fully characterizing the spectrophotometric properties of P. falciparum-infected RBCs by using only 16 specific wavelengths within the visible optical spectra and two different post-processing algorithms. With such an innovative methodology, low-level infections can be detected and quantified, and early- and late-stage development can be clearly distinguished, not only improving the current detection limits but also proving the successful applicability of spectrophotometry for competitive and accurate malaria diagnosis.

Application of a Volumetric Absorptive Microsampling (VAMS)-Based Method for the Determination of Paracetamol and Four of its Metabolites as a Tool for Pharmacokinetic Studies in Obese and Non-Obese Patients.

The pharmacokinetic (PK) profile of a drug is influenced by several factors, which can lead to a suboptimal dosing regimen in specific patient populations. As obesity becomes increasingly prevalent, it is important that optimized dosing schemes are available for these patients. To set up such dosing schemes, PK studies should be performed in this population. Regarding paracetamol (acetaminophen [APAP]), obese patients would benefit from a tailored dosing scheme, as both the volume of distribution and metabolism are increased compared with non-obese patients. This includes metabolism by cytochrome P450 2E1, which is involved in APAP-associated hepatotoxicity. To decrease the burden for patients in these PK studies, finger-prick sampling could be used. The aim of this study was to compare the quantitative determination of APAP and four metabolites in different blood-based matrices and to determine if capillary dried blood samples, collected directly following finger-prick, could serve as a tool to investigate APAP PK in obese and non-obese patients. In this study, we performed a clinical validation of methods for the determination of APAP and four of its metabolites (APAP-glucuronide, APAP-sulfate, APAP-mercapturate, and APAP-cysteine) in blood, plasma, and dried blood. The latter was obtained by volumetric absorptive microsampling (VAMS), either starting from the venous blood or collected directly following a finger-prick. Results were compared between the different matrices and, in addition, blood:plasma (B:P) ratios were determined for the different analytes. Liquid and dried venous blood results were in good agreement. Furthermore, differences between capillary (finger-prick) and venous VAMS blood samples remained limited for most analytes. However, for APAP-cysteine, caution should be paid to the interpretation of concentrations in (dried) blood. With the exception of APAP, concentrations were higher in plasma compared with blood, with B:P ratios ranging between 0.52 and 0.65. A time-dependent change in median B:P ratio was observed for APAP and APAP-cysteine. Additionally, a time-dependent trend was seen for APAP, as well as for APAP-glucuronide and APAP-mercapturate, for the distribution between capillary and venous blood. We demonstrated that finger-prick sampling is a viable alternative to conventional venous blood sampling to investigate the PK of APAP and its metabolites in obese and non-obese patients.

TH3.1 Implementation of a home finger-prick CEA test for follow-up of colorectal cancer - a pilot study of patient perspectives

Abstract Aim NICE guidance advocates 6 monthly CEA blood testing following curative colorectal resection. This usually takes place through face to face appointments with a phlebotomist, with associated monetary and resource cost to local services, as well as impacting on patient lives. This project piloted use of self-taken finger-prick blood tests in this patient population, to assess feasibility, patient perspectives and preferences. Methods During colorectal outpatient clinics, patients undergoing face to face CEA surveillance in primary care were offered postal finger-prick assessment. Recruitment stopped once 50 patients had been recruited. Recruited patients were sent finger-prick blood testing kits with pre-paid return packaging. Follow-up questionnaires were undertaken to assess patient perspectives and future preferences. Results 67.6% (50/74) of eligible patients agreed to participate. 76.0% (38/50) of patients successfully completed finger-prick CEA assessment. 46.8% (22/47) of patients felt they would prefer finger-prick rather than phlebotomy for future CEA testing, whilst 19.1% (9/47) had no preference. 38.3% (18/47) patients felt finger-prick testing was worse than their previous experience. No significant differences in preference existed between patients aged &amp;lt;65 and 65+. Qualitative data showed difficulties with pain, discomfort and sample collection. Patients felt that finger-prick samples were convenient and easier to fit in with their lives. Conclusions Whilst some patients prefer finger-prick CEA assessment, there are significant numbers for whom it is challenging, unnecessary or less preferable. Finger-prick CEA testing may represent a future strategy for reducing burden of follow-up blood tests on resources, but this would currently be acceptable only to limited patient groups.

Postal methods for monitoring HbA1c in diabetes mellitus: a protocol for systematic review.

Worldwide there are an estimated 463 million people with diabetes. In the UK people with diabetes are offered annual review, which includes monitoring of haemoglobin A1c (HbA1c). This can identify people with diabetes who are not meeting their glycaemic targets, enabling early intervention. Those who do not attend these reviews often have poorer health outcomes. During the COVID-19 pandemic, there was a 77% reduction in monitoring of HbA1c in the UK. It is hypothesised that people with diabetes could take finger-prick samples at home for measurement of HbA1c. This study will examine the agreement and correlation of capillary HbA1c values compared with a venous reference standard. It will explore reliability and repeatability of capillary HbA1c testing methods, as well as the direction of effect of storage variables. The study will also explore patient acceptability and safety. It will look at capillary blood methods that would be suitable for posting. A systematic review will be undertaken. The core terms of 'Diabetes', 'HbA1c' and 'Capillary sampling' will be used to search MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science Core Collection, Google Scholar, OpenGrey, and other grey literature, from database inception until 2021. Risk of bias will be assessed using the 'COSMIN Risk of Bias tool to assess the quality of studies on reliability and measurement error'. A narrative synthesis will be produced to explore whether there are viable postal alternatives to venous sampling, as well as exploring acceptability and safety of patient self-collection.

Point-of-care haematological monitoring during treatment with clozapine

Abstract Objectives Patients treated with clozapine are required to have regular venous blood samples taken to measure white blood cell (WBC) and neutrophil counts to reduce the risk of agranulocytosis. The need for regular venous blood sampling can deter patients and clinicians from treatment with clozapine. Finger prick sampling offers patients a simpler and less invasive technique that is likely to be more acceptable. We undertook to evaluate a novel point of care testing (POCT) device which measures WBC and neutrophil counts using a small volume of capillary blood from a finger prick sample. Methods A total of 215 patients who were being treated with clozapine and were having a venous blood sample taken for haematological monitoring also provided a fingerprick capillary blood sample. The capillary and venous samples were tested using the Sight OLO® POCT analyser, and the venous sample also tested using a standard laboratory method. Results For both the WBC and the neutrophil counts, there was a strong correlation between the results from the standard laboratory venous method and the POCT assay (R=0.94 and 0.95, respectively for capillary blood samples, and R=0.98 for both WBC and neutrophil counts for venous blood samples). Compared with the standard laboratory venous blood method, mean biases were −1.0×109/L for WBC and −0.5×109/L for neutrophils for the capillary blood POCT method, and −0.4×109/L for WBC and −0.4×109/L for neutrophils for the venous blood POCT method. Overall, 6 of 215 (2.8%) of patients had levels below clozapine monitoring thresholds (WBC &lt;3.5×109/L and Neutrophils &lt;1.5×109/L) by capillary blood, and 5 (2.3%) by venous blood by POCT. Of these, 2 had sub-threshold counts on the standard laboratory method. Conclusions The POCT analyser provided results for both WBC and neutrophil counts that were comparable with those from a standard venous blood laboratory method. Using POCT devices may make haematological monitoring easier in patients being treated with clozapine, and thereby increase the use of clozapine in the treatment of schizophrenia.

AB0369 CORRELATION OF THE FIRST LATERAL FLOW-BASED POINT OF CARE TEST TO QUANTIFY INFLIXIMAB AND ANTI-INFLIXIMAB ANTIBODIES IN A FINGER PRICK SAMPLE WITH THE REFERENCE ELISA TECHNIQUE

BackgroundCurrent techniques to monitor clinical response may require several days and centralised facilities, which may cause delays in effective therapeutic decisions. Therefore, the use of a rapid decentralized test will facilitate patient management and improve patient care.ObjectivesThe goal of this study was to validate the use of capillary blood in a real point-of-care (POC) setting for rheumatic patients under infliximab treatment by using Promonitor Quick lateral flow (LF) tests. Results were compared to the Promonitor ELISA reference technique in serum samples used by centralised laboratories.MethodsA prospective, observational study was designed to evaluate the performance of a rapid LF test (Promonitor Quick IFX, Progenika, Spain). 160 infliximab treated rheumatology consecutive patients (400 samples) were recruited in two hospitals in Galicia, Spain. Prior to the infusion, a finger prick sample was obtained and analysed. Anti-infliximab antibodies were also determined with Promonitor Quick ANTI-IFX1-4. Results were read with the automated portable PQreader instrument. Additionally, a serum sample was collected for subsequent comparative analysis with either LF or ELISA tests.Qualitative (positive (PPA) and negative (NPA) agreements) and quantitative (Pearson correlation and bias) performance of the LF test was compared to ELISA, as well as between different specimens following CLSI EP09-A3.ResultsOverall agreement between Promonitor Quick IFX finger prick and ELISA test was 91% (88% PPA; 100% NPA). The quantitative comparison showed a good correlation (Pearson correlation coefficient: 0.85 and observed bias: 25%) (Table 1).Table 1.Performance results: infliximab drugQualitative ComparisonN*PPANPAoverallPOC finger prick vs ELISA27488%100%91%POC serum vs ELISA28198%100%98%Quantitative ComparisonN*Pearson correlationBiasPOC finger prick vs ELISA1650.8525%POC serum vs ELISA1810.916%*Only samples in the common measurement range for both methods considered.Performance results: anti-infliximab anti-drug antibodiesQualitative ComparisonN*PPANPAoverallPOC finger prick visual vs. PQreader396100%99%99%POC serum visual vs PQreader398100%100%100%POC finger prick PQreader vs ELISA39390%99%98%POC serum PQreader vs ELISA39589%100%99%Similar results were also observed when serum was used with either the LF or the ELISA tests (98% overall agreement, 0.91 correlation coefficient; 6% bias) (Table 1).Overall agreements for visual and automated (PQreader) interpretations with Promonitor Quick ANTI-IFX were 99% and 100% for finger prick and serum specimens, respectively (Table 1).ConclusionPromonitor Quick can be used to reliably quantify infliximab in capillary blood samples and results are comparable to those obtained with the reference ELISA technique. The use of the rapid POC test with finger prick will allow clinicians to monitor their patients in a fully decentralized mode to aid in the decision making process. PQreader is a sensitive portable equipment to report drug as well as antibody levels in the patient samples.

P337 Therapeutic drug monitoring: standardization of Promonitor Quick IFX and Promonitor Quick ADL point of care tests with WHO International Standards for the quantification of infliximab and adalimumab in whole blood and serum

Abstract Background Promonitor Quick IFX and Promonitor Quick ADL are rapid point of care lateral flow tests (LFT) based on a sandwich immunoassay for the quantification of infliximab (IFX) and adalimumab (ADL), respectively, in human whole blood (finger prick or venous) or serum. These tests are to be used as an aid in Therapeutic Drug Monitoring (TDM) of inflammatory bowel disease (IBD) and rheumatic patients under anti-TNFα therapy. The international standards (IS) developed by World Health Organization (WHO) for IFX and ADL allow harmonization and comparability among different assays. The aim of this study, was to show that Promonitor Quick IFX and Promonitor Quick ADL can measure either reference or biosimilar drugs, as well as to evaluate the agreement of Promonitor Quick IFX and Promonitor Quick ADL tests and the WHO IS. Methods Clinical and Laboratory Standards Institute EP10-A3 guidelines were followed to estimate the bias of Promonitor Quick assays when used to quantify IFX or ADL in samples containing the reference drugs, biosimilars or the WHO IS. Briefly, whole blood was spiked with four known concentrations of IFX or ADL, including current clinical decision levels. Ten replicates were measured of each level along two days. Promonitor Quick IFX was evaluated using the reference drug, SB2 and CT-P13 biosimilars, and the WHO IS (NIBSC, 16/170). Promonitor Quick ADL was evaluated using the reference drug, ABP501 and SB5 biosimilars, and the WHO IS (NIBSC, 17/236). Results were obtained in combination with the automated portable reader PQreader. Results Bias was estimated by comparing the observed concentration of drug spiked whole blood samples. Each biosimilar was compared to the reference at the different drug levels tested. Results showed that Promonitor Quick IFX (Table, 1) and Promonitor Quick ADL (Table, 2) are able to measure equivalently any molecule. The accuracy or closeness of the agreement between the result provided by Promonitor Quick IFX and Promonitor Quick ADL and the true value of the measurand was assessed by measuring the IS developed by the WHO (Tables, 1 &amp; 2). Similar results were obtained when serum matrix was used. Conclusion Promonitor Quick IFX and Promonitor Quick ADL allow monitoring of patients treated with IFX and ADL, respectively, with just a finger prick sample. Both tests can quantify reference and biosimilar drugs with equivalent results. Moreover, comparable results were obtained with the WHO IS, and thus, demonstrate that Promonitor Quick tests are suited to accurately determine drug levels at the clinical decision points in both whole blood and serum, proving to be an effective and valuable tool in TDM and immediate decision making in the doctor office or hospitals.

EVALUATION OF THE VALIDITY OF HEMOCUE HB 201+ FOR PREDONATION ASSESSMENT OF LOW AND HIGH HAEMOGLOBIN LEVELS IN BLOOD DONORS: ONE YEAR PROSPECTIVE STUDY IN BLOOD BANK OF GMC DODA

Introduction: Predonation assessment of haemoglobin in blood donors is important to avoid unnecessary rejection of potential blood donors. Compared to the conventional screening methods for haemoglobin assessment the method to be used in blood banks needs to be rapid, sensitive and accurate for both low and high haemoglobin values. Materials and methods: This was a prospective study conducted in blood bank of GMC Doda w.e.f 1st April 2020 to 31st March 2021. Finger prick samples were taken from 1214 potential blood donors and hemoglobin was estimated using HemoCue Hb 201+. Also venous samples of potential blood donors were obtained and run on automated haematologyanalysers. The values were compared. Male donors with haemoglobin in the range of 12.5g/dl -18.5g/dl and females with hemoglobin in the range of 12.5g/dl -16.5g/dl were considered fit for donation. Results: We analyzed that haemoglobin levels measured by HemoCue Hb 201+ were higher than those measured by automated haematologyanalyser. We found a significant correlation between the standard method and HemoCue Hb 201+ for haemoglobin levels less than 12.5 g/dL. However the correlation was found to be less for high haemoglobin levels &gt;18.5g/dl. Sixty percent of donors, who had haemoglobin levels higher than upper limit were unnecessarily rejected accounting for high deferral rate. Conclusion: We concluded that HemoCue Hb 201+ was suitable for screening for low haemoglobin in blood donors. Male predominance among blood donors and topography of this particular area accounts for donors with haemoglobin values near upper limit which were falsely deferred on the basis of HemoCue Hb 201+. Also testing with this method was found to be expensive, so it was recommended that qualitative methods should be used for primary screening among blood donors and accurate quantitative methods to be used only when qualitative methods fail.

Solid-phase recombinase polymerase amplification using ferrocene-labelled dNTPs for electrochemical detection of single nucleotide polymorphisms

Hypertrophic cardiomyopathies (HCM) are the principal cause of sudden cardiac death in young athletes and it is estimated that 1 in 500 people have HCM. The aim of this work was to develop an electrochemical platform for the detection of HCM-associated SNP in the Myosin Heavy Chain 7 (MYH7) gene, in fingerprick blood samples. The platform exploits isothermal solid-phase primer elongation using recombinase polymerase amplification with either individual or a combination of four ferrocene-labelled nucleoside triphosphates. Four thiolated reverse primers containing a variable base at their 3’ end were immobilised on individual gold electrodes of an array. Following hybridisation with target DNA, solid phase recombinase polymerase amplification was carried out and primer elongation incorporating the ferrocene labelled oligonucleotides was only detected at one of the electrodes, thus facilitating identification of the SNP under interrogation. The assay was applied to the direct detection of the SNP in fingerprick blood samples from eight different individuals, with the results obtained corroborating with next generation sequencing. The ability to be able to robustly identify the SNP using a 10 μL fingerprick sample, demonstrates that SNP discrimination is achieved using low femtomolar (ca. 8 × 105 copies DNA) levels of DNA.