Wouter Marcel Tiel Groenestege

Background: Prostate-specific antigen (PSA) is a biomarker used for detection, screening, and follow-up of prostate cancer. Traditional PSA quantification requires venipuncture, which poses challenges in collection, storage, and transportation. Dried blood spot (DBS) technology presents a promising alternative for measuring PSA levels, potentially facilitating telemedicine, and large-scale screening programs. Methods: PSA concentrations were measured in paired capillary finger-stick DBS and venous serum samples from 75 patients using a Siemens immunochemistry analyzer. For DBS samples, PSA was extracted using PBS prior to analysis. Additional validation of stability, hematocrit effects, precision, and limits of blank and quantitation was performed according to corresponding Clinical and Laboratory Standards Institute standards. Results: The DBS PSA assay demonstrated good analytical performance, with total CVs of 4.5% and 6.1% at PSA concentrations of 11.5 µg/L and 3.8 µg/L, respectively. Limit of blank, limit of detection, and limit of quantitation were 0.24 µg/L, 0.28 µg/L, and 0.70 µg/L, respectively. Method comparison showed strong agreement between venous serum and finger-stick DBS (R2 = 0.987) with minimal bias. Stability studies showed that PSA remained stable for up to 31 days between −20°C and +30°C. Hematocrit affected measured PSA concentrations, but results remained within predefined total allowable error limits across 0.25–0.50 L/L. Variations in double spotting, blood volume, and number of spots did not affect PSA concentrations with a consistent trend. Conclusions: PSA can be accurately measured from finger-stick DBS on an automated high-throughput immunochemistry analyzer. This method is less invasive for patients and may facilitate at-home self-sampling supporting (tele)diagnostics, screening, and follow-up.

Objectives: Measuring creatinine levels is essential for assessing kidney function. However, traditional venous sampling poses challenges in terms of sample collection, storage, and transportation. Recently, dried blood spot (DBS) analysis has emerged as a potential alternative for measuring creatinine levels, although its clinical application remains limited. Creatinine measurements from DBS could facilitate chronic kidney disease screening, medication management, and at-home patient monitoring. Methods: Precision and hematocrit effect were assessed according to Clinical and Laboratory Standards Institute protocols to validate creatinine measurements in DBS. Subsequently, the protocol was applied in a method comparison involving 115 patients. Lastly, robustness was assessed by investigating creatinine stability over time and the influence of spotting effects. Results: Creatinine measurements in DBS resulted in low bias and correcting for hematocrit further improved accuracy. A comparison of creatinine and estimated glomerular filtration rate (eGFR) between venous plasma and finger stick DBS showed an R ² of 0.97 and 0.86, respectively. Moreover, sensitivity and specificity for detecting decreased eGFR (2 ) were 91 and 96 %, respectively. Creatinine remained stable in DBS for up to a month at −20 °C and 4 °C, up to six days at 20 °C, and one day at 37 °C. Finally, spotting effects such as double spotting had negligible effects. Conclusions: In conclusion, creatinine from DBS can be analyzed using an automated high-throughput chemistry analyzer, enabling accurate eGFR classification. This method may support blood sampling at home for screening programs, patient follow-up, and medication management.

Background: Medical resource allocation is important to ensure availability of care, especially in challenging circumstances like a pandemic. In fields of unpredictable care demand such as obstetrics, forecasting may help manage scarce resources. Objective: The development, validation, and implementation of a regional birth forecasting tool to support obstetrical staff planning in the Utrecht region during the COVID-19 pandemic. Methods: We combined predicted birth dates retrieved from Saltro, a large regional primary care laboratory, with data from the Dutch national perinatal registry (Perined) and Statistics Netherlands for model development. We created and implemented an HTML tool visualizing these forecasts, which were discussed during the regional acute obstetric health care network meetings. Six months after implementation, we assessed the impact of the tool using an evaluative stakeholder meeting. Results: We achieved a performance accuracy ( R ) of 0.45, 0.61, and 0.67 (all actual number of births within 95% CI) forecasting the number of births in the region, pooled in 1-, 2-, and 3-weekly bins, respectively. After presenting these findings to stakeholders, we implemented a forecasting tool using the 2-week bin model. The evaluative stakeholder meeting proved that the tool improved communication, awareness of health care need, and collaborations among health care providers in the Utrecht region. Additionally, stakeholders identified additional applications, such as communication with patients and training of obstetric health care providers. Conclusions: Implementation of a forecasting tool for the number of births based on available data across the health care system added value to obstetrical care by providing insight into care demand, and increasing communication, awareness, and collaboration between health care providers. Further research should aim at improving regional obstetric acute care by fostering data sharing in order to improve health care demand forecasts.

Objectives: This study examined the comparability of venous and capillary blood samples with regard to routine chemistry analytes. Methods: Venous and capillary blood samples were collected from adult patients to assess comparability of alanine transaminase, albumin, alkaline phosphatase, apolipoprotein B, aspartate aminotransferase, total bilirubin, calcium, chloride, creatin kinase, creatinine, C-reactive protein, ferritin, folic acid, free T4, gamma glutamyltransferase, glucose, high density lipoprotein cholesterol, iron, lipase, lipoprotein a, magnesium, phosphate, postassium, prostate specific antigen, sodium, total cholesterol, total protein, transferrin, triglycerides, thyroid stimulating hormone, urate, urea, vitamin B12 and 25-hydroxyvitamin-D3. Furthermore, hemolysis-icterus-lipemia Index (HIL-Index) was measured for all samples. All measurements were performed using the Siemens Atellica ^® CH or IH Analyzer. Deming regression analysis and mean relative differences between venous and capillary measurements of each analyte were contrasted with the desirable total allowable error (TEa) and Clinical Laboratory Improvement Amendments (CLIA) 2024 proposed acceptance limits for proficiency testing. Results: Deming regression and mean relative differences demonstrated excellent comparability between venous and capillary samples for most measured analytes. Conclusions: Capillary and venous samples showed comparable results for almost all studied chemistry analytes. Of the 33 studied analytes for which TEa criteria where available, 30 met TEa criteria. CLIA 2024 criteria where available for 29 of the studied analytes of which only glucose did not meet the criteria. In conclusion, capillary blood draw is a suitable alternative for venous blood sampling for measuring most of the investigated analytes. This benefits patients with fear of needles and might pave the way for remote self-sampling.

Healthcare practitioners often use distraction techniques to ease children’s anxiety during blood draws. This study explored the effectiveness of a social robot, Softbank Robotics NAO, in reducing anxiety and pain for children aged 4-12 during blood draws. The robot engaged with children using behaviors tailored to the children’s age. Interestingly, results indicated the robot significantly increased anxiety, but pain levels remained unchanged. We argue that this effect may result from the robot’s novelty and that, over the long term, the robot could have a positive impact on anxiety, consistent with other studies. This research underscores the potential of social robots to alleviate children’s anxiety in medical procedures, enhancing patient experience in pediatric healthcare.

C-reactive protein (CRP) is an acute-phase protein involved in inflammation. Furthermore, CRP is an important biomarker used in diagnostics to predict risk of cardiovascular disease (CVD) in addition to monitoring bacterial and viral infections. To measure plasma CRP, venipuncture is still necessitated and has to be performed by trained phlebotomists. As a solution, dried blood spots (DBS) are used for minimally invasive at-home sampling of blood and can be send to diagnostic laboratories by regular mail. In this study, we included 53 patients that 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 allowed to dry. After extraction of DBS, CRP was analyzed on an automated high-throughput chemistry analyzer. Additional validation steps regarding stability, effect of hematocrit, precision, and limits of blank and quantitation were conducted according to corresponding Clinical and Laboratory Standards Institute standards. An excellent regression analysis of R² (95% confidence interval) = 0.986 (0.982–0.989) was found. This enabled correct classification for high CVD risk of all 25 cases with sensitivity (95% CI) of 1.00 (1.00–1.00) and specificity (95% CI) of 0.96 (0.89–1.03) and correct diagnosis of inflammation of 12/13 cases with sensitivity (95% CI) of 0.92 (0.77–1.07) and specificity (95% CI) of 1.00 (1.00–1.00). Furthermore, CRP was found to be stable for 31 days and observed hematocrit variation amongst patients was clinically acceptable. CRP from DBS can be accurately measured on an automated high-throughput chemistry analyzer and used to diagnose inflammation and classify high CVD risk. This method enables individuals to engage in at-home sampling of blood on DBS for (tele)diagnostics, screening programs, patient follow-up, and medication management.

A 34-year-old woman presented to the emergency department with abdominal pain and vaginal bleeding following a positive urine pregnancy test. The patient was referred to the gynecologist. Remarkably, her serum was cola-colored ( Fig. 1). Ultrasonography showed an ectopic pregnancy (EP) in the right fallopian tube and fluid collection intraperitoneally. Salpingectomy revealed a ruptured fallopian tube and hemorrhage embedding the EP.

Leukolysis-related pseudohyperkalemia due to preanalytical procedures may lead to erroneous (or absence of) treatment based on an invalid lab test result. We aimed to obtain a leukocyte threshold above which leukolysis-related pseudohyperkalemia becomes clinical relevant. Secondly, temporal dynamics of treatment-induced leukocyte decrease were studied to allow tailored implementation of laboratory information system (LIS) decision rules based on the leukocyte threshold to avoid leukolysis-related pseudohyperkalemia. Potassium results of AU5811 routine chemistry (Beckman Coulter, Brea, California, USA) and iStat point of care (POC) (Abbott Diagnostics, Chicago, Illinois, USA) analysers were compared, the latter method being insensitive to leukolysis caused by pre-analytical procedures. Potassium results were combined with leukocyte counts obtained using a Cell-Dyn Sapphire haematology analyser (Abbott Diagnostics, Santa Clara, California, USA), resulting in 132 unique data triplets. Regression analysis was performed to establish a leukocyte threshold. The Reference Change Value (√2 x Z x √(CVa2 + CVi2)) was used to calculate maximum allowable difference between routine analyser and POC potassium results (deltamax + 0.58 mmol/L). Temporal analysis on the treatment-induced leukocyte decrease was performed by plotting leukocyte counts in time for all patients above the threshold leukocyte count (N = 41). Established leukocyte threshold was 63 x109/L. Temporal analysis showed leukocyte counts below the threshold within 8 days of treatment for all patients. Based on performed analyses we were able to implement LIS decision rules to reduce pseudohyperkalemia due to preanalytical procedures. This implementation can contribute to a reduction in erroneous (or absence of) treatments in the clinic.