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.

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.

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.

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.

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.

One mouse, one pharmacokinetic profile: quantitative whole blood serial sampling for biotherapeutics.

PURPOSE: The purpose of this study was to validate the approach of serial sampling from one mouse through ligand binding assay (LBA) quantification of dosed biotherapeutic in diluted whole blood to derive a pharmacokinetic (PK) profile. METHODS: This investigation compared PK parameters obtained using serial and composite sampling methods following administration of human IgG monoclonal antibody. The serial sampling technique was established by collecting 10 µL of blood via tail vein at each time point following drug administration. Blood was immediately diluted into buffer followed by analyte quantitation using Gyrolab to derive plasma concentrations. Additional studies were conducted to understand matrix and sampling site effects on drug concentrations. RESULTS: The drug concentration profiles, irrespective of biological matrix, and PK parameters using both sampling methods were not significantly different. There were no sampling site effects on drug concentration measurements except that concentrations were slightly lower in sodium citrated plasma than other matrices. CONCLUSIONS: We recommend the application of mouse serial sampling, particularly with limiting drug supply or specialized animal models. Overall the efficiencies gained by serial sampling were 40-80% savings in study cost, animal usage, study length and drug conservation while inter-subject variability across PK parameters was less than 30%.

On the improvement of blood sample collection at clinical laboratories.

BACKGROUND: Blood samples are usually collected daily from different collection points, such hospitals and health centers, and transported to a core laboratory for testing. This paper presents a project to improve the collection routes of two of the largest clinical laboratories in Spain. These routes must be designed in a cost-efficient manner while satisfying two important constraints: (i) two-hour time windows between collection and delivery, and (ii) vehicle capacity. METHODS: A heuristic method based on a genetic algorithm has been designed to solve the problem of blood sample collection. The user enters the following information for each collection point: postal address, average collecting time, and average demand (in thermal containers). After implementing the algorithm using C programming, this is run and, in few seconds, it obtains optimal (or near-optimal) collection routes that specify the collection sequence for each vehicle. Different scenarios using various types of vehicles have been considered. Unless new collection points are added or problem parameters are changed substantially, routes need to be designed only once. RESULTS: The two laboratories in this study previously planned routes manually for 43 and 74 collection points, respectively. These routes were covered by an external carrier company. With the implementation of this algorithm, the number of routes could be reduced from ten to seven in one laboratory and from twelve to nine in the other, which represents significant annual savings in transportation costs. CONCLUSIONS: The algorithm presented can be easily implemented in other laboratories that face this type of problem, and it is particularly interesting and useful as the number of collection points increases. The method designs blood collection routes with reduced costs that meet the time and capacity constraints of the problem.

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 feasibility and cost of neonatal screening for prenatal alcohol exposure by measuring phosphatidylethanol in dried blood spots.

BACKGROUND: Accurate confirmation of prenatal alcohol exposure (PAE) is required as a diagnostic criterion for the majority of children adversely affected by PAE who do not manifest the physical features associated with fetal alcohol syndrome. A number of ethanol biomarkers have been used to assess PAE, often with suboptimal results. The purpose of this study was to evaluate the feasibility and cost of PAE screening in newborns by measuring phosphatidylethanol (PEth) in dried blood spot (DBS) cards. METHODS: The feasibility of collecting an additional DBS card during routine newborn screening and the background prevalence of PAE were evaluated in a de-identified sample of newborn children delivered at the University of New Mexico Hospital. Electronic orders to collect DBS cards from newborns who continue to bleed after the routine newborn screen, glucose, or hematocrit testing were initiated for all infants delivered during a 4-week time frame. Specimens were sent to a contract laboratory for PEth analysis by liquid chromatography-tandem mass spectrometry. A cost analysis was conducted to compare the cost of PAE screening by PEth in DBS versus PEth in conventional blood specimens and by meconium fatty acid ethyl esters. RESULTS: From 230 collected cards, 201 (87.4%) had at least 1 full blood spot (amount sufficient for PEth analysis), and 6.5% had PEth >20 ng/ml indicative of potential PAE in late pregnancy. PAE screening by PEth in DBS is logistically simpler and less expensive compared with 2 other screening approaches. CONCLUSIONS: These results indicate that screening for PAE in DBS cards is a feasible procedure and that a majority of infants have enough blood after the routine heel prick to fill an additional card. Moreover, screening by PEth analysis from DBS cards is cost-efficient. The acceptability of such screening by parents and corresponding ethical issues remain to be investigated.

Not the usual suspects: addressing layers of vulnerability.

This paper challenges the traditional account of vulnerability in healthcare which conceptualizes vulnerability as a list of identifiable subpopulations. This list of 'usual suspects', focusing on groups from lower resource settings, is a narrow account of vulnerability. In this article we argue that in certain circumstances middle-class individuals can be also rendered vulnerable. We propose a relational and layered account of vulnerability and explore this concept using the case study of cord blood (CB) banking. In the first section, two different approaches to 'vulnerability' are contrasted: categorical versus layered. In the second section, we describe CB banking and present a case study of CB banking in Argentina. We examine the types of pressure that middle-class pregnant women feel when considering CB collection and storage. In section three, we use the CB banking case study to critique the categorical approach to vulnerability: this model is unable to account for the ways in which these women are vulnerable. A layered account of vulnerability identifies several ways in which middle-class women are vulnerable. Finally, by utilizing the layered approach, this paper suggests how public health policies could be designed to overcome vulnerabilities.

Comparison of genomic DNA extraction techniques from whole blood samples: a time, cost and quality evaluation study.

Genomic DNA obtained from patient whole blood samples is a key element for genomic research. Advantages and disadvantages, in terms of time-efficiency, cost-effectiveness and laboratory requirements, of procedures available to isolate nucleic acids need to be considered before choosing any particular method. These characteristics have not been fully evaluated for some laboratory techniques, such as the salting out method for DNA extraction, which has been excluded from comparison in different studies published to date. We compared three different protocols (a traditional salting out method, a modified salting out method and a commercially available kit method) to determine the most cost-effective and time-efficient method to extract DNA. We extracted genomic DNA from whole blood samples obtained from breast cancer patient volunteers and compared the results of the product obtained in terms of quantity (concentration of DNA extracted and DNA obtained per ml of blood used) and quality (260/280 ratio and polymerase chain reaction product amplification) of the obtained yield. On average, all three methods showed no statistically significant differences between the final result, but when we accounted for time and cost derived for each method, they showed very significant differences. The modified salting out method resulted in a seven- and twofold reduction in cost compared to the commercial kit and traditional salting out method, respectively and reduced time from 3 days to 1 hour compared to the traditional salting out method. This highlights a modified salting out method as a suitable choice to be used in laboratories and research centres, particularly when dealing with a large number of samples.

A third troponin T blood sample is not cost-effective in patients with suspected non-ST segment elevation acute coronary syndrome.

BACKGROUND: The diagnosis of acute myocardial infarction requires troponin assessment in at least two blood samples 6-9 hours apart, with an optional third sample 12-24 hours after admission if suspicion is high. Yet, in many institutions, this third sample is routinely drawn. This study aimed to evaluate cost-effectiveness of this third sample of troponin. METHODS: A total of 534 patients with possible Non ST-Elevation Acute Coronary Syndrome (NSTE-ACS) were included. Blood samples for cardiac TroponinT (cTnT) were obtained on arrival, after 6-9 hours, and 12-24 hours after admission. The costs of cTnT analysis, and hospital stay were calculated. RESULTS: Of the 534 patients, 124 had at least one elevated cTnT value. Among these, four patients (3.2%) had cTnT values increased only in the third sample. Based on their risk profile and/or ECG changes, these four patients were eligible for referral to coronary angiography even before the result of the third sample became available. The number of patients whose length of stay was extended solely because of the third sample was 275. Incremental cost of the third blood sample: [534 patients × Euro (EUR) 12 per cTnT analysis] + [275 patients × 0.5 day × EUR 1,550] = EUR 219,533. Approximately 1400 patients with suspected NSTE-ACS are admitted to our department each year. Thus, the total cost per year is: (1,400/534) × EUR 219,533 = EUR 575,555. CONCLUSION: A third troponin sample adds no vital information regarding patients' treatment or investigations plan. On the contrary, it may lead to an unnecessary extension of the admission period and increased costs.

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.

Whole blood and component use in resource poor settings.

Data on blood collection, testing and component preparation has improved worldwide; however, there is limited information on blood utilization from the developing countries. Blood requirement in the Southeast Asia region is 15 million units against a collection of 9.3 million. There is huge diversity in the management of blood transfusion services, the voluntary blood collection (range 40-100%) and proportion of blood separated into components (10-95%). The major indications for transfusion are for emergency obstetric care, surgery, pediatric and trauma patients. The prevalence of thalassemia in this region is high and in India alone 2 million units of packed red cells are required for transfusion to these patients. The Blood Safety Program in India has developed as a component of the National Aids Control Program and has lead to infrastructure development, blood component separation facilities and formulation of a National Blood Policy. In order to facilitate emergency obstetric care nearer home, blood storage centers are being established at primary health care centers. Emerging infectious threats like dengue hemorrhagic fever necessitate platelet transfusion therapy. A few centers in India issue NAT screened blood. It is envisaged to establish a nationally co-ordinated transfusion service for cost-effective quality blood/components for appropriate clinical use.

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.

A point-of-care device for acute kidney injury: a fantastic, futuristic, or frivolous 'measure'?

This Commentary discusses concepts related to the development of the point-of-care (POC) diagnostic system and its advantages and disadvantages. Also discussed are the patient, provider, and financial outcomes that ought to be evaluated before the POC test becomes available for clinical use.

Blood spots as an alternative to whole blood collection and the effect of a small monetary incentive to increase participation in genetic association studies.

BACKGROUND: Collection of buccal cells from saliva for DNA extraction offers a less invasive and convenient alternative to venipuncture blood collection that may increase participation in genetic epidemiologic studies. However, dried blood spot collection, which is also a convenient method, offers a means of collecting peripheral blood samples from which analytes in addition to DNA can be obtained. METHODS: To determine if offering blood spot collection would increase participation in genetic epidemiologic studies, we conducted a study of collecting dried blood spot cards by mail from a sample of female cancer cases (n = 134) and controls (n = 256) who were previously selected for a breast cancer genetics study and declined to provide a venipuncture blood sample. Participants were also randomized to receive either a $2.00 bill or no incentive with the blood spot collection kits. RESULTS: The average time between the venipuncture sample refusal and recruitment for the blood spot collection was 4.4 years. Thirty-seven percent of cases and 28% of controls provided a dried blood spot card. While the incentive was not associated with participation among controls (29% for $2.00 incentive vs. 26% for no incentive, p = 0.6), it was significantly associated with participation among the breast cancer cases (48% vs. 27%, respectively, p = 0.01). There did not appear to be any bias in response since no differences between cases and controls and incentive groups were observed when examining several demographic, work history and radiation exposure variables. CONCLUSION: This study demonstrates that collection of dried blood spot cards in addition to venipuncture blood samples may be a feasible method to increase participation in genetic case-control studies.

A cost-effective screening method for preoperative hyperglycemia.

INTRODUCTION: The preoperative encounter may offer a cost-effective opportunity for diabetes screening. METHODS: Three hundred forty-seven fasting patients had a preoperative glucose measurement determined from blood residue left on the IV needle, measured with an Accu-Chek glucometer (Roche Diagnostics, Indianapolis, IN). RESULTS: After excluding patients with a diabetes history, 4.0% had a glucose measurement between 100 and 125 mg/dL, at a cost of $14.22 per identification, and 1.2% had a glucose measurement more than 125 mg/dL, at a cost of $32.00 per identification. CONCLUSIONS: This preoperative blood glucose screening test was implemented at a cost of approximately one-tenth of current methods.