Microsampling Techniques Suitable for Therapeutic Drug Monitoring of Antipsychotics.

BACKGROUND: Therapeutic drug monitoring (TDM) of antipsychotics for dose titration or detection of noncompliance is not uncommon in daily practice. Normally, TDM implies measuring a drug concentration in venous blood samples. This technique is invasive and requires trained assistants and patients normally need to go to an outpatient clinic. Over the past decades, sensitivity of analytical equipment has improved leading to a growing interest in microsampling techniques. These techniques are minimally invasive, require a small volume (<100 µL), usually result in stable samples, and can be collected by the patient or a caregiver at home. Before a microsampling technique can be used in daily routine, proper method development and a clinical validation study should be performed. METHOD: For this review, the databases of PubMed and Embase were systematically searched. Currently available microsampling techniques for antipsychotics in blood, serum, or plasma are summarized. Subsequently, it has also been assessed whether these techniques are sufficiently validated for TDM monitoring in daily practice. RESULTS: Several microsampling techniques are available today, for example, dried blood spot sampling, dried plasma extraction cards, and volumetric absorptive microsampling. Eighteen studies were identified in which a microsampling technique for 1 or a few antipsychotics was chemically analytically and clinically validated. However, the majority of these studies have relevant shortcomings that mean its usefulness for different antipsychotics is not yet well established. CONCLUSIONS: Microsampling for TDM can be recommended for patients using clozapine. For TDM of other antipsychotics, it is a very promising development.

Extraction of high quality and high yield RNA from frozen EDTA blood.

Peripheral blood RNA profiling, which can reveal systemic changes in gene expression and immune responses to disease onset and progression, is a powerful tool for diagnosis and biomarker discovery. This technique usually requires high quality RNA, which is only obtainable from fresh blood, or frozen blood that has been collected in special RNA-stabilisation systems. The current study aimed to develop a novel protocol to extract high quality RNA from frozen blood that had been collected in the conventional EDTA tubes. We determined that thawing EDTA blood in the presence of cell lysis/RNA stabilisation buffers (Paxgene or Nucleospin) significantly improved RNA quality (RIN) from below 5 to above 7, which to date has not been shown possible. The EDTA-Nucleospin protocol resulted in 5 times higher yield than the EDTA-Paxgene-PreAnalytix method. The average RIN and mRNA expression levels of five different genes including 18 s, ACTB, MCP1, TNFa and TXNIP using this protocol were also indifferent to those from Paxgene blood, suggesting similar RNA quality and blood transcriptome. Moreover, the protocol allows DNA to be extracted simultaneously. In conclusion, we have developed a practical and efficient protocol to extract high quality, high yield RNA from frozen EDTA blood.

The Impact of Blood Sample Processing on Ribonucleic Acid (RNA) Sequencing.

In gene quantification and expression analysis, issues with sample selection and processing can be serious, as they can easily introduce irrelevant variables and lead to ambiguous results. This study aims to investigate the extent and mechanism of the impact of sample selection and processing on ribonucleic acid (RNA) sequencing. RNA from PBMCs and blood samples was investigated in this study. The integrity of this RNA was measured under different storage times. All the samples underwent high-throughput sequencing for comprehensive evaluation. The differentially expressed genes and their potential functions were analyzed after the samples were placed at room temperature for 0h, 4h and 8h, and different feature changes in these samples were also revealed. The sequencing results showed that the differences in gene expression were higher with an increased storage time, while the total number of genes detected did not change significantly. There were five genes showing gradient patterns over different storage times, all of which were protein-coding genes that had not been mentioned in previous studies. The effect of different storage times on seemingly the same samples was analyzed in this present study. This research, therefore, provides a theoretical basis for the long-term consideration of whether sample processing should be adequately addressed.

Hemocultivos contaminados: bundle para lograr proporciones aceptables / Blood cultures contaminated: bundle to achieve acceptable proportions

Introducción. El problema de la contaminación de los hemocultivos es muy frecuente en establecimientos de atención hospitalaria, da lugar a la administración de antibióticos innecesarios y prolonga la hospitalización. Objetivo principal. Aplicar un bundle para reducir la proporción de contaminación de hemocultivos. Objetivo secundario. Realizar una encuesta anónima para detectar oportunidades de mejora en la técnica de extracción de hemocultivos. Metodología. Diseño del estudio: Estudio cuasi experimental que evaluó la proporción de contaminación de hemocultivos antes y después de implementar un bundle propio. Se determinó la proporción basal de contaminación de hemocultivos (ene-jul 2022), se realizó la intervención (agosto 2022) y se estableció la proporción de contaminación post intervención (sep.-abril 2023). Intervención: Se analizó la estructura, procedimiento y conocimiento del personal mediante una encuesta propia para detectar áreas de mejora. Se capacitó, a los técnicos de laboratorio, sobre el procedimiento de la toma de muestra mediante una simulación utilizando un brazo artificial. Se diseñó un bundle de seis medidas, se adaptó el procedimiento de toma de hemocultivo y se capacitó al personal. Análisis estadístico. Se analizó la proporción de hemocultivos contaminados entre los periodos pre y post utilizando Chi2 y la relación entre la proporción del periodo pre y post vs la literatura (3.00% contaminación aceptable) utilizando test Z para una proporción. Se consideró un p<0.05 como estadísticamente significativa. Se utilizo el software Stata 8. Resultados. Durante el estudio se analizaron un total de 3,965 hemocultivos. De estos, 1,978 corresponden al periodo pre-intervención y 1,987 corresponden al periodo post intervención. Durante la pre-intervención se detectaron 61 hemocultivos contaminados (3.08% vs 3.00% bibliografía, p:0.5866) mientras que en la etapa post intervención fue de 30 hemocultivos contaminados (1.51% vs 3.00% bibliografía, p:0.0000). La proporción de hemocultivos contaminados se redujo a la mitad, 3.08% vs 1.51%, p: 0.001. Se realizó una encuesta anónima pre y post intervención logrando mejoras en la técnica de toma de hemocultivos. Conclusión. La implementación del bundle propio para la extracción de hemocultivos, permitió reducir la proporción de contaminación a la mitad. El análisis de la encuesta nos permitió identificar oportunidades de mejora en la técnica de recolección de muestra de hemocultivos

Introduction: Contamination of blood cultures is very common in hospital care settings and results in the administration of unnecessary antibiotics and prolongs hospitalization. Main goal: Apply a bundle to reduce the rate of contamination of blood cultures. Secondary objective: Conduct an anonymous survey to detect opportunities for improvement in the blood culture extraction technique. Methodology: Study design: Quasi-experimental study that evaluated the proportion of blood culture contamination before and after implementing its own bundle. The baseline proportion of blood culture contamination was determined (Jan-July 2022), the intervention was performed (August 2022) and the post-intervention contamination proportion was established (September-April 2023). Intervention: The structure, procedure and knowledge of the staff was analyzed through an own survey to detect areas for improvement. Laboratory technicians were trained on the sample collection procedure through a simulation using an artificial arm. A bundle of six measures was designed: (hand hygiene with alcohol gel, use of common gloves and sterile gloves during extraction, antisepsis with alcoholic chlorhexidine gluconate, marking of the blood culture bottle up to the filling level, disinfection of the bottle cap). blood culture bottle with 70% alcohol, safety-lok kit with vacuum extraction system). The procedure was adapted and staff trained. Statistic analysis: The proportion of contaminated blood cultures between the pre and post periods was analyzed using Chi2 and the relationship between the proportion of the pre and post period vs the literature (3.00% acceptable contamination) using Z test for a proportion. P<0.05 was considered statistically significant. Stata 8 software was used.Results: A total of 3,965 blood cultures were analyzed during the study. Of these, 1,978 correspond to the pre-intervention period and 1,987 correspond to the post-intervention period. During the pre-intervention, 61 contaminated blood cultures were detected (3.08%) while in the post-intervention stage there were 30 contaminated blood cultures (1.51%). The proportion of contaminated blood cultures was reduced by half, 3.08% vs 1.51%, p: 0.001. An anonymous survey was carried out pre and post intervention, achieving improvements in the technique of taking blood cultures. Conclusion: The implementation of the own bundle for the extraction of blood cultures allowed the contamination rate to be reduced by ha

A Bioinspired and Cost-Effective Device for Minimally Invasive Blood Sampling.

Conventional venipuncture is invasive and challenging in low and middle-income countries. Conversely, point-of-care devices paired with fingersticks, although less invasive, suffer from high variability and low blood volume collection. Recently approved microsampling devices address some of these issues but remain cost-prohibitive for resource-limited settings. In this work, a cost-effective microsampling device is described for the collection of liquid blood with minimal invasiveness and sufficient volume retrieval for laboratory analyses or immediate point-of-care testing. Inspired by the anatomy of sanguivorous leeches, the single-use device features a storage compartment for blood collection and a microneedle patch hidden within a suction cup. Finite Element Method simulations, corroborated by mechanical analyses, guide the material selection for device fabrication and design optimization. In piglets, the device successfully collects ≈195 µL of blood with minimal invasiveness. Additionally, a tailor-made lid and adapter enable safe fluid transportation and integration with commercially available point-of-care systems for on-site analyses, respectively. Taken together, the proposed platform holds significant promise for enhancing healthcare in the pediatric population by improving patient compliance and reducing the risk of needlestick injuries through concealed microneedles. Most importantly, given its cost-effective fabrication, the open-source microsampling device may have a meaningful impact in resource-limited healthcare settings.

Prototype and evaluation of automatic fingertip-blood-sampling system that uses fingertip blood-vessel images to determine puncture position.

We are developing an automatic fingertip-blood-sampling system to reduce the burden on trained medical personnel. For this system to withdraw a consistent volume of sampled blood for blood tests, we developed a mechanism for our system to select and puncture the vicinity of a large blood vessel from the blood-vessel image of an individual's fingertip. We call this mechanism the fingertip-vessel-puncture mechanism. From the results of an experiment in which the fingertips of 20 individuals (men and women in their 20 s to 60 s) were manually punctured at near and far locations from the blood vessel selected with our mechanism, the following conclusions were obtained. The fingertip-vessel-puncture mechanism tends to increase the volume of sampled blood, thus is effective in sampling more than 650 µL of blood for automatic blood analyzers. It was also found that it is more effective in increasing the volume of sampled blood in the men and those who were younger.

Five days serum glucose stability at room-temperature in centrifuged fast-clotting serum tubes and the comparability with glucose in heparin-plasma and plasma containing citrate-stabilizer.

Glucose measurement plays a central role in the diagnosis of gestational diabetes mellitus (GDM). Because of earlier reports of overestimation of glucose in the widely used tubes containing granulated glycolysis inhibitor, the study assessed the performance of fast-clotting serum tubes as an alternative sample for the measurement of glucose. Glucose concentration in fast-clotting serum was compared to lithium-heparin plasma placed in an ice-water slurry after sample collection and glucose stability at room-temperature was studied. Blood samples from 30 volunteers were drawn in four different types of tubes (serum separator tubes, fast-clotting serum tubes, lithium-heparin tubes and sodium fluoride, EDTA and a citrate buffer (NaF-EDTA-citrate) tubes, all from Greiner Bio-One). Lithium-heparin tubes were placed in an ice-water slurry until centrifugation in accordance with international recommendations and centrifuged within 10 min. After centrifugation, glucose was measured in all tubes (timepoint T0) and after 24, 48, 72, 96 and 120 h of storage at 20-22 °C. NaF-EDTA-citrate plasma showed significant overestimation of glucose concentration by 4.7% compared to lithium-heparin plasma; fast-clotting serum showed glucose concentrations clinically equivalent to lithium-heparin plasma. In fast-clotting serum tubes, mean bias between glucose concentration after 24, 48, 72, 96 and 120 h and T0 was less than 2.4%. All individual differences compared to T0 were less than 6.5%. The results fulfill the acceptance criteria for sample stability based on biological variation. Fast-clotting serum tubes can be an alternative for the measurement of glucose in diagnosis and management of GDM and diabetes mellitus, especially when prolonged transportation is necessary.

LC-MS/MS measurement of endogenous steroid hormones and phase II metabolites in blood volumetric absorptive microsampling (VAMS) for doping control purposes.

BACKGROUND: Volumetric Absorptive Microsampling (VAMS) is emerging as a valuable technique in the collection of dried biological specimens, offering a potential alternative to traditional sampling methods. The objective of this study was to assess the suitability of 30 µL VAMS for the measurement of endogenous steroid hormones. METHODS: A novel LC-MS/MS method was developed for the quantification of 18 analytes in VAMS samples, including main endogenous free steroids and phase II metabolites of androgens. The method underwent validation in accordance with ISO/IEC 17025:2017 and World Anti-Doping Agency (WADA) requirements. Subsequently, it was applied to authentic VAMS samples obtained from 20 healthy volunteers to assess the stability of target analytes under varying storage conditions. RESULTS: The validation protocol assessed method's selectivity, matrix effect, extraction recovery, quantitative performance, carry-over and robustness. The analysis of authentic samples demonstrated the satisfactory stability of monitored steroids in VAMS stored at room temperature, 4 °C, -20 °C and -80 °C for up to 100 days and subjected to up to 3 freezing-thawing cycles. CONCLUSIONS: The validated LC-MS/MS method demonstrated its suitability for the measurement of steroids in dried blood VAMS. The observed stability of steroidal compounds suggests promising prospects for future applications of VAMS, both in anti-doping contexts and clinical research.

Effects of blood sample storage time, temperature, anti-coagulants and blood stabiliser on lymphocyte phenotyping.

Medical diagnostic laboratories have come under further scrutiny to ensure quality standards of their service and external quality assurance (EQA) programs involving multiple laboratories have been used to gauge this quality based on a consensus. However, because of the geographical distances within a country or internationally, cell surface marker expressions may change due to time delays and transport temperatures. Attention was given to this issue some decades ago and hence requires a re-evaluation in consideration of updated methods, reagents and instruments for flow cytometry and phenotyping. We have undertaken an extensive study to examine the effects of various conditions on blood storage akin to that experienced by patient samples as well as EQA programs, examining expression of lymphocyte surface markers, CD3, CD4, CD8, CD2, CD19, CD20, CD16/56 and HLA-DR. Assessment of lithium-heparin anticoagulated whole blood showed an increase in percentage of CD3+ and CD8+ T cells and a decrease in CD16/56+ NK cells after storage at room temperature (RT) for 24 and/or 48 h. In comparison, storage at 4°C led to a decrease in percentage of CD4+ and increase in percentage of CD8+ cells. The low temperature also caused an increase in percentage of B cells (CD19+, CD20+). While storage at RT did not alter levels of HLA-DR+ CD3+ T cells, there was a significant increase in percentage of these cells after 48 h. Changes were also seen at both temperatures when EDTA was used as an anti-coagulant. Assessment of blood treated with a stabiliser, normally used in the EQA samples (Streck Cell Preservative), reduced the range of lymphocyte subsets affected, with only CD2+ and CD20+ cells being significantly different at both temperatures, We conclude that 24-48 h storage/transport can affect the percentage of CD3+, CD4+ T cells, CD8+ T cells, B cells, NK cells and HLADR+ T cells which can be minimised by using the blood stabiliser as per EQA programs and we emphasise the need to adopt this in the processing of patients' blood samples.

Pre-analytical stability of selected biochemical analytes in serum of horses and oxen stored at -20°C.

BACKGROUND: Delays between blood collection and analysis are inevitable, and samples are always stored in the refrigerator. The current study aimed to evaluate the stability of serum total cholesterol (TC), triglycerides (TG), total protein (TP), albumin and urea (URA) in horses and oxen after storage at -20°C. METHODS: Sera from apparently healthy 20 male horses and 20 oxen were obtained and aliquots of serum were divided into 3 portions. The first tube was used for baseline (T0) measurement of analyte values, whereas the other two tubes, T1 and T2, were stored at -20°C for 1 and 2 months, respectively, and analyte measurement was done. RESULTS: Results showed that the stability of TP (g/dL), URA (mg/dL) and TC (mg/dL) in oxen was statistically significant (p < 0.05). In horses, the stability of URA (mg/dL), TP (g/dL) and TG (mg/dL) were also statistically significant (p < 0.05). Additionally, URA and TC in oxen exceed TEa following measurement at T2 and TG in horses following measurement at T1 and T2. CONCLUSION: Laboratories should consider the storage temperature and time for specific analytes among animals. Therefore, stability studies at various storage temperatures and times are recommended to fully validate the stability of the analytes.

The effect of the simulated intrauterine sound on behavioral and physiological indices of pain during capillary blood sampling for screening preterm infants: a randomized clinical trial study.

INTRODUCTION: Due to medical procedures, preterm infants are at high risk for side effects of pain. In this regard, heel lancing for capillary blood sampling is a common painful procedure. The present study was conducted to assess the effectiveness of a simulated intrauterine sound on behavioral and physiological indices of pain due to heel-prick blood sampling in preterm infants. METHODS: A double­blind randomized clinical trial (RCT) was conducted. The data were collected from September 23 to December 22, 2019. We measured the effect of a simulated intrauterine sound on changes in the behavioral and physiological parameters of pain (heart rate, SPO2) caused by heel lance that was measured 5 min before the intervention, during the sampling, and 5 min after the procedure. We measured behavioral pain by video recording the infants' faces and then the scoring neonatal infant pain scale (NIPS). Heart rate and SPO2 were measured using a pulse oximeter device. The data were analyzed using analysis of variance (ANOVA) and independent t­test in SPSS software version 20.0. RESULTS: Eighty infants were randomized (40 in each group). Mean scores NIPS during and after intervention were in the intervention group (3.55 ± 0.84, 95% CI: 3.30-3.80(, and (1.15 ± 0.84, 95%: 0.95-1.35) and in the control group (5.57 ± 0.95, 95% CI:5.30-5.85) and (3.00 ± 0.98) respectively. There were significant differences in scores of NIPS between the two study groups during (p < 0.001) and five min after heel lancing (p < 0.001). Mean scores of heart rate in the three phases of before, during, and five min after the intervention were respectively in the intervention group (127.57 ± 4.45, 95% CI:126.27-128.99), (131.07 ± 6.54, 95% CI:129.20-133.22), (128.45 ± 5.15, 95% CI:127.02-130.07) and in the control group (128.67 ± 4.57, 95% CI:127.32-130.07), (136.07 ± 7.24, 95% CI:133.90-138.37), and (132.42 ± 6.47, 95% CI:130.37-134.49). There were significant differences in heart rate between the intervention and the control group during (p = 0.002) and five min after the heel lance (p = 0.003). Mean scores of SPO2 in the three phases of baseline, during, and five min after the intervention were respectively in the intervention group (96.72 ± 0.93, 95% CI:96.42-97.00), (91.47 ± 1.46, 95% CI:91.05-91.92), (94.17 ± 1.03, 95% CI:93.22-94.00) and in the control group (96.6 ± 0.84, 95% CI:96.35-96.85), (91.5 ± 1.24, 95% CI:91.12-91.87), and (93.60 ± 1.27, 95% CI:93.85-94.50). CONCLUSION: This study showed that the simulated intrauterine sound reduces the behavioral pain and heart rate in the intervention group during and after heel lance. These results suggest using the method during the painful heel lancing to reduce pain parameters in preterm infants.

Fingerprick volumetric absorptive microsampling for therapeutic drug monitoring of antiseizure medications: Reliability and real-life feasibility in epilepsy patients.

Volumetric absorptive microsampling (VAMS) is increasingly proposed as a clinically reliable therapeutic drug monitoring (TDM) sampling methodology. The study aimed to establish the reliability and real-life feasibility of patient self-collected capillary VAMS for TDM of antiseizure medication (ASMs), using plasma ASMs concentrations from venous blood as a reference standard. Nurses collected venous and capillary blood samples using VAMS. Afterward, persons with epilepsy (PWE) performed VAMS sampling by themselves. All samples were analyzed by UHPLC-MS/MS. We performed a cross-validation study, comparing ASMs concentrations obtained by VAMS nurses and patients' self-collected versus plasma through Bland-Altman analysis and Passing-Bablok regression. We enrolled 301 PWE (M: F 42.5%:57.5%; mean age 44±16 years), treated with 13 ASMs, providing a total of 464 measurements. Statistical analysis comparing VAMS self-collected versus plasma ASMs concentrations showed a bias close to zero and slope and intercept values indicating a good agreement for CBZ, LCS, LEV, LTG, OXC, PB, and PHT, while a systematic difference between the two methods was found for VPA, PMP, TPM and ZNS. This is the first study showing the reliability and feasibility of the real-world application of PWE self-collected VAMS for most of the ASMs considered, giving a promising basis for at-home VAMS applications.

Acceptability of plasma ammonia results when samples are not transported and processed under ideal conditions.

BACKGROUND: It is recommended that samples for plasma ammonia analysis are kept chilled and processed promptly as in vitro metabolism causes falsely elevated results. Rejection of unsuitable samples can cause delayed diagnosis and treatment of hyperammonaemia with potentially serious clinical consequences. The Metabolic Biochemistry Network (MetBioNet) hyperammonaemia guideline recommends analysis of samples not collected under ideal conditions and reporting with appropriate comments. An audit found that some laboratories did not follow this guidance. An investigation was performed into whether storage at controlled room temperature and delayed sample processing affected interpretation of plasma ammonia results. METHODS: Eleven healthy volunteers provided informed consent. Blood was taken from each into 14 paediatric EDTA blood sample tubes, one placed immediately on ice, the others in a rack at room temperature. The chilled and baseline room temperature samples were centrifuged and plasma analysed by the Roche Ammonia (NH3L2) method. Samples stored at room temperature were analysed at 10-min intervals up to 2 h. RESULTS: Baseline room temperature ammonia was higher than in the chilled sample (19 ± 6.6 µmol/L [mean ± standard deviation] and 18 ± 6.6 µmol/L, respectively). Ammonia increased further by 0.09 ± 0.02 µmol/L per minute to 30 ± 8.4 µmol/L at 2 h. No result was above the reference range (50 µmol/L). No healthy subject with normal baseline ammonia would have been erroneously identified as having hyperammonaemia. CONCLUSIONS: Results support MetBioNet guidance that laboratories accept blood samples for ammonia analysis which are not processed under ideal conditions.

Plasma Glucose Concentrations in Different Sampling Tubes Measured on Different Glucose Analysers.

INTRODUCTION: The German Diabetes Association recommends using sampling tubes with citrate and fluoride additives to diagnose diabetes by oral glucose tolerance test to inhibit glycolysis. The effect of different tubes on measurement results was assessed. MATERIALS AND METHODS: In a first study, an oral glucose tolerance test was performed on 41 participants without anamnestically known diabetes. Venous blood was sampled in two different tubes with citrate/fluoride additives from different manufacturers and one with only lithium-heparin additive. A second study with 42 participants was performed to verify the initial results with an adapted design, in which a third tube with citrate buffer was used, and glucose measurements were performed on two additional devices of another analyser model. Samples were centrifuged either immediately (<5 min incubation time) or after 20 min or 4 h. All glucose measurements were performed in plasma. Glucose concentrations in lithium-heparin tubes with<5 min incubation time served as baseline concentrations. RESULTS: In the first study, glucose concentrations in one of the citrate/fluoride tubes were similar to the baseline. In the other citrate/fluoride tube, markedly lower concentrations (approximately - 5 mg/dL (- 0.28 mmol/L)) were measured. This was reproduced in the verification study for the same analyser, but not with the other analyser model. Lithium-heparin tubes centrifuged after 20 and 240 min showed systematically lower glucose concentrations. CONCLUSIONS: The results confirm that glycolysis can be effectively inhibited in citrate/fluoride-containing sampling tubes. However, glucose measurement results of one analyser showed a relevant negative bias in tubes containing liquid citrate buffer.

A Mathematical Algorithm for Dried Blood Spot Quality Assessment and Results concerning Quality from a Newborn Screening Program.

BACKGROUND: In addition to newborn screening, dried blood spots (DBSs) are used for a wide variety of analytes for clinical, epidemiological, and research purposes. Guidelines on DBS collection, storage, and transport are available, but it is suggested that each laboratory should establish its own acceptance criteria. METHODS: An optical scanning device was developed to assess the quality of DBSs received in the newborn screening laboratory from 11 maternity wards between 2013 and 2018. The algorithm was adjusted to agree with the visual examination consensus of experienced laboratory personnel. Once validated, the algorithm was used to categorize DBS specimens as either proper or improper. Improper DBS specimens were further divided based on 4 types of specimen defects. RESULTS: In total, 27 301 DBSs were analyzed. Compared with an annual DBS rejection rate of about 1%, automated scanning rejected 26.96% of the specimens as having at least one defect. The most common specimen defect was multi-spotting (ragged DBS, 19.13%). Among maternity wards, improper specimen rates varied greatly between 5.70% and 49.92%. CONCLUSIONS: Improper specimen rates, as well as the dominant type of defect(s), are mainly institution-dependent, with various maternity wards consistently showing specific patterns of both parameters over time. Although validated in agreement with experienced laboratory personnel consensus, automated analysis rejects significantly more specimens. While continuous staff training, specimen quality monitoring, and problem-reporting to maternities is recommended, a thorough quality assessment strategy should also be implemented by every newborn screening laboratory. An important role in this regard may be played by automation in the form of optical scanning devices.

Generic UPLC-MS/MS and Gyrolab assays with blood microsampling for pharmacokinetic assessments of therapeutic antibodies in mice.

Serial blood sampling from one animal is useful to understand relationship between pharmacokinetics (PK) and pharmacological or toxicological events in individual animals. To assess its feasibility in mice, two therapeutic antibodies were used to evaluate impacts by different blood sampling methods, sampling sites, and assay platforms on PK. Denosumab and Panitumumab were intravenously administered to mice and only 0.05 mL of blood sample per point was collected from jugular vein or tail vein. Blood samples were collected serially from a mouse or collected by traditional composite sampling from each mouse. Plasma concentrations of the two drugs were assayed by a generic ligand binding assay using Gyrolab or by a generic ultra-performance liquid chromatography with tandem mass spectrometry. The two assay platforms showed acceptable accuracy and precision and gave comparable PK parameters of the drugs, suggesting that both assays were successfully applied to the PK assessments. Comparable results in the PK profiles were noted between serial and composite blood samplings and differences in the two sampling sites did not impact PK. These findings suggest that microsampling combined with generic assays is useful to assess PK profiles of therapeutic antibodies in mice.

Novel method for determining when a field-collected donor unit is sufficiently full.

BACKGROUND: Whole blood (WB) collections can occur downrange for immediate administration. An important aspect of these collections is determining when the unit is sufficiently full. This project tested a novel method for determining when a field collection is complete. METHODS: The amount of empty space at the top of WB units, destined to become LTOWB or separated into components, that were collected at blood centers or hospitals was measured by holding a WB unit off the ground and placing the top of a piece of string where the donor tubing entered the bag. The string was marked where it intersected the top of the column of blood in the bag and measured from the top. The WB units were also weighed. RESULTS: A total of 15 different bags, two of which were measured in two different filling volumes, from 15 hospitals or blood centers were measured and weighed. The most commonly used blood bag, Terumo Imuflex SP, had a median string length of 9 mm (range: 2-24 mm) and weighed a median of 565.1 g (range: 524.8-636.7 g). CONCLUSION: Pieces of string can be precut to the appropriate length depending on the type of bag before a mission where field WB collections might be required and a mark placed on the bag before the collection commences to indicate when the unit is full.

Blood Samples from Midline Catheters: Clinically Equivalent to Venipuncture.

PowerGlide Pro™ Midline Catheters, manufactured by Becton Dickinson, are marketed as capable of obtaining blood specimens. However, there is insufficient research to validate the laboratory results collected from these specialty catheters. The purpose of this research study was to determine whether blood samples obtained via venipuncture and samples obtained directly from a midline catheter are clinically equivalent. A qualitative study was completed per recommendations published in Clinical and Laboratory Standards Institute (CLSI) standards EP-05-A3 to determine whether the 2 modalities are clinically equivalent. A 12-point correlation study was performed, comparing blood results from phlebotomy venipuncture and midline catheter blood draws for 20 successful participants. Results were compared with an EP Evaluator. Report interpretation was completed using the 2-instrument comparison module to determine whether the 2 methods were clinically equivalent. All correlated specimens resulted within the medically acceptable total allowable error, proving the 2 methods clinically equivalent. The study concluded that blood draws from midline catheters are clinically equivalent to venipuncture and are an acceptable form of specimen collection for laboratory studies.

Validation of Mitra® VAMS® as a blood collection technique for trace elements analysis using ICP-MS/MS.

Background: Clinical dosage of toxic and essential elements in blood is well established and the collection method is still by venipuncture. This method has drawbacks and is not suited for everyone. Volumetric absorptive microsampling (VAMS) has been shown to have advantages over venipuncture. Materials & methods: Using inductively coupled plasma tandem mass spectrometry, a method for quantifying elements in whole blood sampled on VAMS was developed/validated. Method's performance was assessed by comparison with whole blood results. Results: Validation and performance assessment tests tend to show that most of the targeted elements provides accurate and reproducible results comparing to a method of reference. Conclusion: Overall, VAMS presents good preliminary results to eventually become an alternative to venipuncture for blood sampling for some trace elements analysis purposes.