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.

The Binns Program for Cord Blood Research: A novel model of cord blood banking for academic biomedical research.

Umbilical cord blood is an important graft source in the treatment of many genetic, hematologic, and immunologic disorders by hematopoietic stem cell transplantation. Millions of cord blood units have been collected and stored for clinical use since the inception of cord blood banking in 1989. However, the use of cord blood in biomedical research has been limited by access to viable samples. Here, we present a cost-effective, self-sustaining model for the procurement of fresh umbilical cord blood components for research purposes within hospital-affiliated academic institutions.

Financial analysis of large-volume delayed sampling to reduce bacterial contamination of platelets.

BACKGROUND: Effective and financially viable mitigation approaches are needed to reduce bacterial contamination of platelets in the US. Expected costs of large-volume delayed sampling (LVDS), which would be performed by a blood center prior to shipment to a hospital, were compared to those of pathogen reduction (PR), point-of-release testing (PORt), and secondary bacterial culture (SBC). METHODS: Using a Markov-based decision-tree model, the financial and clinical impact of implementing all variants of LVDS, PR, PORt, and SBC described in FDA guidance were evaluated from a hospital perspective. Hospitals were assumed to acquire leukoreduced apheresis platelets, with LVDS adding $30 per unit. Monte Carlo simulations were run to estimate the direct medical costs for platelet acquisition, testing, transfusion, and possible complications associated with each approach. Input parameters, including test sensitivity and specificity, were drawn from existing literature and costs (2018US$) were based on a hospital perspective. A one-way sensitivity analysis varied the assumed additional cost of LVDS. RESULTS: Under an approach of LVDS (7-day), the total cost per transfused unit is $735.78, which falls between estimates for SBC (7-day) and PORt. Assuming 20,000 transfusions each year, LVDS would cost $14.72 million annually. Per-unit LVDS costs would need to be less than $22.32 to be cheaper per transfusion than all other strategies, less than $32.02 to be cheaper than SBC (7-day), and less than $196.19 to be cheaper than PR (5-day). CONCLUSIONS: LVDS is an effective and cost-competitive approach, assuming additional costs to blood centers and associated charges to hospitals are modest.

A simplified blood culture sampling protocol for reducing contamination and costs: a randomized controlled trial.

OBJECTIVES: Blood culture contamination carries risks for patients, such as unnecessary antimicrobial therapy and other additional hazards and costs. One method shown to be effective in reducing contamination is initial blood specimen diversion during collection. We hypothesized that initial blood specimen diversion without a designated device or procedure would suffice for reduction in blood culture contamination rate. METHODS: From 1 September 2017 through to 6 September 2018, we conducted a randomized controlled trial to assess the effect of an initial-specimen diversion technique (ISDT) on the rate of blood-culture contamination by changing the order of sampling using regular vacuum specimen tubes instead of commercially available sterile diversion devices. We included adults from whom the treating physician planned to take blood cultures and additional blood chemistry tests. Additionally, we evaluated the potential economic benefits of an ISDT. This was a researcher-initiated trial, Clinicaltrials.gov NCT03088865. RESULTS: In all, 756 patients were enrolled. This method, compared with the standard procedure in use at our medical centre, reduced contamination by 66% (95% CI 17%-86%), from 20/400 (5%) with the standard method to 6/356 (1.6%) with the ISDT, without compromising detection of true bloodstream infection and at no additional cost. Hospital-wide implementation of ISDT was associated with a 1.1% saving in hospitalization days. CONCLUSIONS: We offer this novel approach as a simple, cost-effective measure to reduce risks to patient safety from contaminated blood cultures, without the need for using costly devices.

Increasing DNA Isolation Performance from Blood Cells Using a Modified Commercial Low-Cost Reagent.

BACKGROUND: Genomic studies facilitate comprehension of the pathophysiology, diagnosis, and treatment of chronic diseases. Such studies require sufficient and good quality DNA isolated from a large number of blood samples. This study attempts to obtain a high-quality genomic DNA isolated from a large number of blood samples using a simple and cheap method. METHODS: The EasyPure® Genomic DNA Kit (Transgen Biotech) was modified to increase the amount of DNA recovery: a few steps and two additional column elutions were added to the original manufacturer´s procedure. RESULTS: The amount of DNA isolated from frozen blood samples increased by an average of 56%. Its 260/280 ratio and electrophoretic mobility properties make it suitable for genomic studies. CONCLUSIONS: A relatively low-cost commercial column and a simple modification of the manufacturer´s protocol, provided a simple and cheap procedure to isolate high-quality DNA from a large number of blood samples suitable for genomic studies.

Thromboelastography testing in mice following blood collection from facial vein and cardiac puncture.

: Blood collection is critical for mouse research studies particularly in hemostatic testing. Cardiac puncture; a standard effective method requires anesthesia and is a terminal procedure while facial vein technique allows multiple collections. Thromboelastography (TEG) is a global hemostasis test, provides a dynamic real-time picture of coagulation. However, TEG experiments in mice require large number of animals and may not allow pre/postinterventions assessment. In this study, we aimed to investigate the feasibility of facial vein sampling for TEG analysis as an alternative to cardiac puncture and examined the impact on coagulation results. Blood samples were obtained from a total of 10 C57BL/6 and CD-1 mice via cardiac puncture and a total of another eight mice of similar strains via facial vein sampling. We compared TEG parameters in both methods using descriptive statistics and the Student t test. Results show no significant difference in any of the TEG parameters between cardiac and facial vein blood indicating the two methods are comparable. Facial vein sampling provides a less costly alternative to cardiac puncture. It is a suitable blood collection method for pre/postinterventions or follow-up studies and it better addresses reduction and refinement goals in mouse studies. A larger study to evaluate the sex or strain and genetic background differences will be valuable.

Economic Implications of Pathogen Reduced and Bacterially Tested Platelet Components: A US Hospital Budget Impact Model.

BACKGROUND: US FDA draft guidance includes pathogen reduction (PR) or secondary rapid bacterial testing (RT) in its recommendations for mitigating risk of platelet component (PC) bacterial contamination. An interactive budget impact model was created for hospitals to use when considering these technologies. METHODS: A Microsoft Excel model was built and populated with base-case costs and probabilities identified through literature search and a survey of US hospital transfusion service directors. Annual costs of PC acquisition, testing, wastage, dispensing/transfusion, sepsis, shelf life, and reimbursement for a mid-sized hospital that purchases all of its PCs were compared for four scenarios: 100% conventional PCs (C-PC), 100% RT-PC, 100% PR-PC, and 50% RT-PC/50% PR-PC. RESULTS: Annual total costs were US$3.64, US$3.67, and US$3.96 million when all platelets were C-PC, RT-PC, or PR-PC, respectively, or US$3.81 million in the 50% RT-PC/50% PR-PC scenario. The annual net cost of PR-PC, obtained by subtracting annual reimbursements from annual total costs, is 6.18% above that of RT-PC. Maximum usable shelf lives for C-PC, RT-PC, and PR-PC are 3.0, 5.0, and 3.6 days, respectively; hospitals obtain PR-PC components earliest at 1.37 days. CONCLUSION: The model predicts minimal cost increase for PR-PC versus RT-PC, including cost offsets such as elimination of bacterial detection and irradiation, and reimbursement. Additional safety provided by PR, including risk mitigation of transfusion-transmission of a broad spectrum of viruses, parasites, and emerging pathogens, may justify this increase. Effective PC shelf life may increase with RT, but platelets can be available sooner with PR due to elimination of bacterial detection, depending on blood center logistics.

The East-West blood trade : How the German Democratic Republic obtained foreign currency with blood products (1983-1990).

Using the East-West blood trade of the German Democratic Republic (GDR) in the 1980s as an example, this study aims to show what kind of problems arise when trade agreements are made with authoritarian regimes, where transparency is lacking and the general public is not informed about the trading conditions. Files from the Ministry of Health and the Foreign Trade Ministry show the extent, aims, and scope of the blood exports to the West. Within the East-West trade, blood was regarded solely as a commercial good; ethical concerns played no part. The blood trade was the most important income source of unscheduled foreign currency for the GDR health sector. People were asked to donate for the wellbeing of society and without receiving remuneration. They were unaware that their blood was an object of commercial trade. Most of the revenue was put into secret accounts of the GDR Foreign Trade Ministry or went to Western intermediaries. The regulations for blood deliveries often challenged the blood donation institutes; they lacked donors, modern techniques/equipment, and personal. Buyers in the West repeatedly complained about the quality of the blood products. The Western intermediaries sold the goods to bulk-buyers, predominantly in German-speaking countries.

Adverse Economic Impact Associated With Blood Culture Contamination in a Pediatric Emergency Department.

BACKGROUND: Blood culture contamination (BCC) leads to unnecessary interventions including hospitalization, antibiotic administration and additional laboratory tests. Previous studies in adults revealed that BCC was associated with unnecessary financial expenditures. However, information pertaining to the pediatric population is limited. Therefore, we investigated the details of the adverse economic impact associated with BCC in a pediatric emergency department (ED) in Japan. METHODS: This study was a retrospective, observational study. We collected data on blood cultures performed in patients 18 years of age in a pediatric ED. Medical records of patients with positive blood cultures were reviewed, and the information regarding adverse events related to BCC was extracted. Medical costs related to BCC were estimated from the data. RESULTS: In total, 13,139 sets of blood cultures were performed from April 2013 to June 2016, and 141 cases (1.1%) of BCC were identified. Among these, 106 patients (75%) experienced at least 1 adverse event associated with BCC. The total medical cost due to BCC was 4,076,713 Japanese yen. Multifaceted approaches targeting ED physicians including lectures on optimal blood collection methods and monthly feedback on BCC rates were effective in reducing the BCC rate and its related costs. CONCLUSIONS: Interventions associated with BCC were common and accounted for significant adverse economic impact on pediatric patients. Regular education and monitoring were effective in reducing BCC and its related costs.

Evaluation of a novel micro-sampling device, Mitra™, in comparison to dried blood spots, for analysis of praziquantel in Schistosoma haematobium-infected children in rural Côte d'Ivoire.

Pharmacokinetic (PK) studies with paediatric populations are increasing in importance for drug development. However, conventional PK sampling methods are characterised by invasiveness and low patient adherence, unsuitable for use with sensitive population, such as children. Mitra™ is a novel volumetric absorptive micro-sampling device, which offers an alternative to the dried blood spotting (DBS) technique, a current popular sampling technique within PK studies. We tested Mitra™ for the first time in the framework of a randomised controlled trial in rural Côte d'Ivoire. Thirty-five school-aged children, infected with Schistosoma haematobium, were sampled with both DBS and Mitra™, at 10 time points after treatment with praziquantel (PZQ). An extraction method for PZQ from Mitra™ was developed, optimised and validated. Analytes, namely R- and S-praziquantel (R-/SPZQ) and the main human metabolite, R-trans-4-OH-praziquantel, were measured using liquid chromatography-tandem mass spectrometry and the results were compared with Bland-Altman analysis to determine agreement between matrices. PK parameters, such as maximal plasma concentration and area under the concentration-time curve, were estimated using non-compartmental analysis. While we observed strong positive correlation (R2 > 0.98) and agreement between both matrices within the calibration line and quality control samples, Mitra™ revealed higher concentrations of all the analytes in the majority of patients' samples compared to DBS sampling, namely 63% samples for RPZQ, 49% for SPZQ and 78% for the metabolite were overestimated. While T1/2 and Tmax were in agreement between both matrices, area under the curve and maximal blood concentration were up to 2× higher for Mitra™ samples, with P < 0.005 for all parameters except Cmax of SPZQ, which was not significantly different between the two matrices. The reasons for the higher PZQ concentrations, more pronounced in incurred Mitra™ samples compared to spiked samples, are yet to be fully explored. Mitra™ appears superior to DBS in terms of simplicity and practicality however labelling issues and the high price of Mitra™ are difficult to overlook.

The economic impact of poor sample quality in clinical chemistry laboratories: results from a global survey.

Background Despite advances in clinical chemistry testing, poor blood sample quality continues to impact laboratory operations and the quality of results. While previous studies have identified the preanalytical causes of lower sample quality, few studies have examined the economic impact of poor sample quality on the laboratory. Specifically, the costs associated with workarounds related to fibrin and gel contaminants remain largely unexplored. Methods A quantitative survey of clinical chemistry laboratory stakeholders across 10 international regions, including countries in North America, Europe and Oceania, was conducted to examine current blood sample testing practices, sample quality issues and practices to remediate poor sample quality. Survey data were used to estimate costs incurred by laboratories to mitigate sample quality issues. Results Responses from 164 participants were included in the analysis, which was focused on three specific issues: fibrin strands, fibrin masses and gel globules. Fibrin strands were the most commonly reported issue, with an overall incidence rate of ∼3%. Further, 65% of respondents indicated that these issues contribute to analyzer probe clogging, and the majority of laboratories had visual inspection and manual remediation practices in place to address fibrin- and gel-related quality problems (55% and 70%, respectively). Probe maintenance/replacement, visual inspection and manual remediation were estimated to carry significant costs for the laboratories surveyed. Annual cost associated with lower sample quality and remediation related to fibrin and/or gel globules for an average US laboratory was estimated to be $100,247. Conclusions Measures to improve blood sample quality present an important step towards improved laboratory operations.

Use of a simple, inexpensive device for collection of blood during acute normovolaemic haemodilution in a Jehovah's Witness patient.

Postoperative anaemia is a concern for patients who refuse blood products or have rare blood types. Acute normovolaemic haemodilution (ANH) is a potential solution for these challenging populations. However, protocols for ANH provide limited detail on preparation of blood collection systems. This report describes a novel protocol for ANH and an example of a patient who clearly benefited from ANH.

Evaluation of a low-cost procedure for sampling, long-term storage, and extraction of RNA from blood for qPCR analyses.

BACKGROUND: In large clinical trials, where RNA cannot be extracted immediately after sampling, preserving RNA in whole blood is a crucial initial step in obtaining robust qPCR data. The current golden standard for RNA preservation is costly and designed for time-consuming column-based RNA-extraction. We investigated the use of lysis buffer for long-term storage of blood samples for qPCR analysis. METHODS: Blood was collected from 13 healthy adults and diluted in MagMAX lysis/binding solution or PAXgene Blood RNA tubes and stored at -20 °C for 0, 1, or 4 months before RNA extraction by the matching method. RNA integrity, yield and purity were evaluated and the methods were compared by subsequent analyses of the gene expression levels of 18S, ACTB, IL1B, IL1RN, IL1R2, and PGK1 using qPCR. RESULTS: The MagMAX system extracted 2.3-2.8 times more RNA per mL blood, with better performance in terms of purity, and with comparable levels of integrity relative to the PAXgene system. Gene expression analysis using qPCR of 18S, ACTB, IL1B, IL1RN, IL1R2, and the promising blood-specific reference gene, PGK1, revealed negligible differences (<1-fold) between the samples stored in MagMAX lysis/binding solution over time and between samples stored and extracted by the two systems. CONCLUSIONS: The MagMAX system can be used for storage of human blood for up to 4 months and is equivalent to the PAXgene system for RNA extraction. It furthermore, provides a means for significant cost reduction in large clinical trials.

Cost analysis of strategies to reduce blood culture contamination in the emergency department: sterile collection kits and phlebotomy teams.

OBJECTIVE: Blood culture collection practices that reduce contamination, such as sterile blood culture collection kits and phlebotomy teams, increase up-front costs for collecting cultures but may lead to net savings by eliminating downstream costs associated with contamination. The study objective was to compare overall hospital costs associated with 3 collection strategies: usual care, sterile kits, and phlebotomy teams. DESIGN: Cost analysis. SETTING: This analysis was conducted from the perspective of a hospital leadership team selecting a blood culture collection strategy for an adult emergency department (ED) with 8,000 cultures drawn annually. METHODS: Total hospital costs associated with 3 strategies were compared: (1) usual care, with nurses collecting cultures without a standardized protocol; (2) sterile kits, with nurses using a dedicated sterile collection kit; and (3) phlebotomy teams, with cultures collected by laboratory-based phlebotomists. In the base case, contamination rates associated with usual care, sterile kits, and phlebotomy teams were assumed to be 4.34%, 1.68%, and 1.10%, respectively. Total hospital costs included costs of collecting cultures and hospitalization costs according to culture results (negative, true positive, and contaminated). RESULTS: Compared with usual care, annual net savings using the sterile kit and phlebotomy team strategies were $483,219 and $288,980, respectively. Both strategies remained less costly than usual care across a broad range of sensitivity analyses. CONCLUSIONS: EDs with high blood culture contamination rates should strongly consider evidence-based strategies to reduce contamination. In addition to improving quality, implementing a sterile collection kit or phlebotomy team strategy is likely to result in net cost savings.

Volumetric absorptive microsampling: a dried sample collection technique for quantitative bioanalysis.

Volumetric absorptive microsampling (VAMS) is a novel approach to obtaining a dried blood sample for quantitative bioanalysis that overcomes the area bias and homogeneity issues associated with conventional dried blood spot (DBS) sample when a subpunch is taken. The VAMS sampler absorbs a fixed volume of blood (∼10 µL) in 2-4 s with less than 5% volume variation across the hematocrit range of 20-70% with low tip-to-tip variability. There is no evidence of selective absorption by the tip of the plasma component over whole blood. Recommendations for best practice when collecting samples were developed based upon the results of tests examining a number of potential abuse scenarios.

The cost of blood collection in Greece: an economic analysis.

OBJECTIVE: The goal of this study was to estimate the cost of production of 1 unit of blood from a National Health Service perspective in Greece. METHODS: In agreement with guidelines, the cost of blood production in this study accounted only for the resources expended for collection, processing, laboratory testing, and storage. Hence, the costs associated with donor recruitment, pretransfusion preparation, transfusion administration, follow-up management of adverse events, and other long-term relevant costs were not taken into consideration. The indirect cost of blood donations for donors (productivity loss) was also considered. A questionnaire was used to collect data regarding personnel time, annual blood quantities collected, percentage of wastage, utilization of consumables, institutional overhead, information technology expenditure, medical equipment utilized, nuclear acid tests, and other factors. Data gathered by 53 hospitals across the country were assessed. A model was constructed with economic data collected by the National School of Public Health and the Ministry of Health. All data refer to the year 2013. RESULTS: The weighted mean direct cost of producing 1 unit of blood was estimated at €131.49 (SD, €22.12; minimum/maximum, €94.96-€239.20). The mean total indirect cost was estimated at €34 per unit of blood. The cost distribution was positively skewed (skewness, 1.642 [0.327]). The major cost component was the cost of personnel, accounting for 32.5% of total costs, and the average of blood unit wastage was estimated at 4.90%. There were no differences between the cost of producing 1 unit of blood in Athens compared with the rest of the country (Mann-Whitney test, P = 0.341). CONCLUSIONS: This study suggests that the cost of producing 1 unit of blood is not insignificant. These figures need to be complemented with those concerning the cost of transfusion to have a complete picture of producing and using 1 unit of blood locally.