The preanalytical optimization of blood cultures: a review and the clinical importance of benchmarking in 5 Belgian hospitals.

PubMed

Willems, Elise; Smismans, Annick; Cartuyvels, Reinoud; Coppens, Guy; Van Vaerenbergh, Kristien; Van den Abeele, Anne-Marie; Frans, Johan

2012-05-01

Bloodstream infections remain a major challenge in medicine. Optimal detection of pathogens is only possible if the quality of preanalytical factors is thoroughly controlled. Since the laboratory is responsible for this preanalytical phase, the quality control of critical factors should be integrated in its quality control program. The numerous recommendations regarding blood culture collection contain controversies. Only an unambiguous guideline permits standardization and interlaboratory quality control. We present an evidence-based concise guideline of critical preanalytical determinants for blood culture collection and summarize key performance indicators with their concomitant target values. In an attempt to benchmark, we compared the true-positive rate, contamination rate, and collected blood volume of blood culture bottles in 5 Belgian hospital laboratories. The true-positive blood culture rate fell within previously defined acceptation criteria by Baron et al. (2005) in all 5 hospitals, whereas the contamination rate exceeded the target value in 4 locations. Most unexpected, in each of the 5 laboratories, more than one third of the blood culture bottles were incorrectly filled, irrespective of the manufacturer of the blood culture vials. As a consequence of this shortcoming, one manufacturer recently developed an automatic blood volume monitoring system. In conclusion, clear recommendations for standardized blood culture collection combined with quality control of critical factors of the preanalytical phase are essential for diagnostic blood culture improvement. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparative biomarker expression and RNA integrity in biospecimens derived from radical retropubic and robot-assisted laparoscopic prostatectomies.

PubMed

Ricciardelli, Carmela; Bianco-Miotto, Tina; Jindal, Shalini; Dodd, Thomas J; Cohen, Penelope A; Marshall, Villis R; Sutherland, Peter D; Samaratunga, Hemamali; Kench, James G; Dong, Ying; Wang, Hong; Clements, Judith A; Risbridger, Gail P; Sutherland, Robert L; Tilley, Wayne D; Horsfall, David J

2010-07-01

Knowledge of preanalytic conditions that biospecimens are subjected to is critically important because novel surgical procedures, tissue sampling, handling, and storage might affect biomarker expression or invalidate tissue samples as analytes for some technologies. We investigated differences in RNA quality, gene expression by quantitative real-time PCR, and immunoreactive protein expression of selected prostate cancer biomarkers between tissues from retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic prostatectomy (RALP). Sections of tissue microarray of 23 RALP and 22 RRP samples were stained with antibodies to androgen receptor (AR) and prostate-specific antigen (PSA) as intersite controls, and 14 other candidate biomarkers of research interest to three laboratories within the Australian Prostate Cancer BioResource tissue banking network. Quantitative real-time PCR was done for AR, PSA (KLK3), KLK2, KLK4, and HIF1A on RNA extracted from five RALP and five RRP frozen tissue cores. No histologic differences were observed between RALP and RRP tissue. Biomarker staining grouped these samples into those with increased (PSA, CK8/18, CKHMW, KLK4), decreased (KLK2, KLK14), or no change in expression (AR, ghrelin, Ki67, PCNA, VEGF-C, PAR2, YB1, p63, versican, and chondroitin 0-sulfate) in RALP compared with RRP tissue. No difference in RNA quality or gene expression was detected between RALP and RRP tissue. Changes in biomarker expression between RALP and RRP tissue exist at the immunoreactive protein level, but the etiology is unclear. Future studies should account for changes in biomarker expression when using RALP tissues, and mixed cohorts of RALP and RRP tissue should be avoided.

History of the preanalytical phase: a personal view

PubMed Central

Guder, Walter G.

2014-01-01

In the 70ies of the last century, ther term “preanalytical phase” was introduced in the literature. This term describes all actions and aspects of the “brain to brain circle” of the medical laboratory diagnostic procedure happening before the analytical phase. The author describes his personal experiences in the early seventies and the following history of increasing awareness of this phase as the main cause of “laboratory errors”. This includes the definitions of influence and interference factors as well as the first publications in book, internet, CD-Rom and recent App form over the past 40 years. In addition, a short summary of previous developments as prerequesits of laboratory diagnostic actions is described from the middle age matula for urine collection to the blood collection tubes, anticoagulants and centrifuges. The short review gives a personal view on the possible causes of missing awareness of preanalytical causes of error and future aspects of new techniques in regulation of requests to introduction of quality assurance programs for preanalytical factors. PMID:24627712

Standardizing in vitro diagnostics tasks in clinical trials: a call for action.

PubMed

Lippi, Giuseppe; Simundic, Ana-Maria; Rodriguez-Manas, Leocadio; Bossuyt, Patrick; Banfi, Giuseppe

2016-05-01

Translational research is defined as the process of applying ideas, insights and discoveries generated through basic scientific inquiry to treatment or prevention of human diseases. Although precise information is lacking, several lines of evidence attest that up to 95% early-phase studies may not translate into tangible outcomes for improving clinical management. Major theoretical hurdles exist in the translational process, but is it also undeniable that many studies may have failed for practical reasons, such as the use of inappropriate diagnostic testing for evaluating efficacy, effectiveness or safety of a given medical intervention, or poor quality in laboratory testing. This can generate biased test results and result in misconceptions during data interpretation, eventually leading to no clinical benefit, possible harm, and a waste of valuable resources. From a genuine economic perspective, it can be estimated that over 10 million euros of funding may be lost each year in clinical trials in the European Union due to preanalytical and analytical problems. These are mostly attributions to the heterogeneity of current guidelines and recommendations for the testing process, to the poor evidence base for basic pre-analytical, analytical and post-analytical requirements in clinical trials, and to the failure to thoughtfully integrate the perspectives of clinicians, patients, nurses and diagnostic companies in laboratory best practices. The most rational means for filling the gap between what we know and what we practice in clinical trials cannot discount the development of multidisciplinary teams including research scientists, clinicians, nurses, patients associations and representative of in vitro diagnostic (IVD) companies, who should actively interplay and collaborate with laboratory professionals to adapt and disseminate evidence-based recommendations about biospecimen collection and management into the research settings, from preclinical to phase III studies.

Pre-analytical Factors Influence Accuracy of Urine Spot Iodine Assessment in Epidemiological Surveys.

PubMed

Doggui, Radhouene; El Ati-Hellal, Myriam; Traissac, Pierre; El Ati, Jalila

2018-03-26

Urinary iodine concentration (UIC) is commonly used to assess iodine status of subjects in epidemiological surveys. As pre-analytical factors are an important source of measurement error and studies about this phase are scarce, our objective was to assess the influence of urine sampling conditions on UIC, i.e., whether the child ate breakfast or not, urine void rank of the day, and time span between last meal and urine collection. A nationwide, two-stage, stratified, cross-sectional study including 1560 children (6-12 years) was performed in 2012. UIC was determined by the Sandell-Kolthoff method. Pre-analytical factors were assessed from children's mothers by using a questionnaire. Association between iodine status and pre-analytical factors were adjusted for one another and socio-economic characteristics by multivariate linear and multinomial regression models (RPR: relative prevalence ratios). Skipping breakfast prior to morning urine sampling decreased UIC by 40 to 50 μg/L and the proportion of UIC < 100 μg/L was higher among children having those skipped breakfast (RPR = 3.2[1.0-10.4]). In unadjusted analyses, UIC was less among children sampled more than 5 h from their last meal. UIC decreased with rank of urine void (e.g., first vs. second, P < 0.001); also, the proportion of UIC < 100 μg/L was greater among 4th rank samples (vs. second RPR = 2.1[1.1-4.0]). Subjects' breakfast status and urine void rank should be accounted for when assessing iodine status. Providing recommendations to standardize pre-analytical factors is a key step toward improving accuracy and comparability of survey results for assessing iodine status from spot urine samples. These recommendations have to be evaluated by future research.

A guide for measurement of circulating metabolic hormones in rodents: Pitfalls during the pre-analytical phase

PubMed Central

Bielohuby, Maximilian; Popp, Sarah; Bidlingmaier, Martin

2012-01-01

Researchers analyse hormones to draw conclusions from changes in hormone concentrations observed under specific physiological conditions and to elucidate mechanisms underlying their biological variability. It is, however, frequently overlooked that also circumstances occurring after collection of biological samples can significantly affect the hormone concentrations measured, owing to analytical and pre-analytical variability. Whereas the awareness for such potential confounders is increasing in human laboratory medicine, there is sometimes limited consensus about the control of these factors in rodent studies. In this guide, we demonstrate how such factors can affect reliability and consequent interpretation of the data from immunoassay measurements of circulating metabolic hormones in rodent studies. We also compare the knowledge about such factors in rodent studies to recent recommendations established for biomarker studies in humans and give specific practical recommendations for the control of pre-analytical conditions in metabolic studies in rodents. PMID:24024118

Attitudes and Perceptions of Cancer Patients Toward Biospecimen Donation for Cancer Research: A Cross-Sectional Survey Among Chinese Cancer Patients.

PubMed

He, Na; Guo, Yan; He, Min; Qiang, Wanmin; Li, Haixin

2017-08-01

High-quality biospecimen collection from consented patients is crucial for cancer research activities. Patients' attitudes and willingness toward specimen donation influence high-quality biospecimen collection for cancer research activities. We carried out a cross-sectional study among randomly selected patients from 11 cancer departments of Tianjin Medical University Cancer Institute and Hospital between August 2014 and August 2015. A total of 784 patients were included to complete a 30-item self-administered survey. We evaluated the patients' willingness to consider providing leftover samples and additional samples for cancer research purposes. Among 784 patients, 683 (87.1%) and 653 (83.3%) were willing to donate leftover tissue and surplus blood after diagnosis, respectively. Six hundred thirty-one (80.5%) were favorably disposed to consider donating both tissue and blood samples for future cancer research. Female patients showed less willingness to donate biospecimens or related clinical data for research. First-hospitalized or older patients were less willing to provide leftover biospecimens or additional blood samples or even clinical data for research. By contrast, patients with a higher education level were more likely to donate leftover tissues after biopsy or surgery for research activities. Most Chinese cancer patients were willing to consider donating blood and tissue samples for cancer research. Several factors, including age, gender, first hospitalization, and education level, can influence their willingness to donate biospecimens. We need to provide proper education to increase understanding of patients in biobanking activities. This study provides novel empirical data on the likelihood of donating surplus and additional biospecimens and clinical health information among Chinese cancer patients.

The procurement, storage, and quality assurance of frozen blood and tissue biospecimens in pathology, biorepository, and biobank settings

PubMed Central

Shabihkhani, Maryam; Lucey, Gregory M.; Wei, Bowen; Mareninov, Sergey; Lou, Jerry J.; Vinters, Harry V.; Singer, Elyse J.; Cloughesy, Timothy F.; Yong, William H.

2014-01-01

Well preserved frozen biospecimens are ideal for evaluating the genome, transcriptome, and proteome. While papers reviewing individual aspects of frozen biospecimens are available, we present a current overview of experimental data regarding procurement, storage, and quality assurance that can inform the handling of frozen biospecimens. Frozen biospecimen degradation can be influenced by factors independent of the collection methodology including tissue type, premortem agonal changes, and warm ischemia time during surgery. Rapid stabilization of tissues by snap freezing immediately can mitigate artifactually altered gene expression and, less appreciated, protein phosphorylation profiles. Collection protocols may be adjusted for specific tissue types as cellular ischemia tolerance varies widely. If data is not available for a particular tissue type, a practical goal is snap freezing within 20 minutes. Tolerance for freeze-thaw events is also tissue type dependent. Tissue storage at −80°C can preserve DNA and protein for years but RNA can show degradation at 5 years. For −80°C freezers, aliquots frozen in RNAlater or similar RNA stabilizing solutions is a consideration. It remains unresolved as to whether storage at −150°C provides significant advantages relative to −80°C. Histologic quality assurance of tissue biospecimens is typically performed at the time of surgery but should also be conducted on the aliquot to be distributed because of tissue heterogeneity. Biobanking protocols for blood and its components are highly dependent on intended use and multiple collection tube types may be needed. Additional quality assurance testing should be dictated by the anticipated downstream applications. PMID:24424103

SEER Cancer Registry Biospecimen Research: Yesterday and Tomorrow

PubMed Central

Altekruse, Sean F.; Rosenfeld, Gabriel E.; Carrick, Danielle M.; Pressman, Emilee J.; Schully, Sheri D.; Mechanic, Leah E.; Cronin, Kathleen A.; Hernandez, Brenda Y.; Lynch, Charles F.; Cozen, Wendy; Khoury, Muin J.; Penberthy, Lynne T.

2014-01-01

The National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) registries have been a source of biospecimens for cancer research for decades. Recently, registry-based biospecimen studies have become more practical, with the expansion of electronic networks for pathology and medical record reporting. Formalin-fixed paraffin-embedded specimens are now used for next-generation sequencing and other molecular techniques. These developments create new opportunities for SEER biospecimen research. We evaluated 31 research articles published during 2005–2013 based on author confirmation that these studies involved linkage of SEER data to biospecimens. Rather than providing an exhaustive review of all possible articles, our intent was to indicate the breadth of research made possible by such a resource. We also summarize responses to a 2012 questionnaire that was broadly distributed to the NCI intra- and extramural biospecimen research community. This included responses from 30 investigators who had used SEER biospecimens in their research. The survey was not intended to be a systematic sample, but instead to provide anecdotal insight on strengths, limitations, and the future of SEER biospecimen research. Identified strengths of this research resource include biospecimen availability, cost, and annotation of data, including demographic information, stage, and survival. Shortcomings include limited annotation of clinical attributes such as detailed chemotherapy history and recurrence, and timeliness of turnaround following biospecimen requests. A review of selected SEER biospecimen articles, investigator feedback, and technological advances reinforced our view that SEER biospecimen resources should be developed. This would advance cancer biology, etiology, and personalized therapy research. PMID:25472677

Pre-analytical and analytical variation of drug determination in segmented hair using ultra-performance liquid chromatography-tandem mass spectrometry.

PubMed

Nielsen, Marie Katrine Klose; Johansen, Sys Stybe; Linnet, Kristian

2014-01-01

Assessment of total uncertainty of analytical methods for the measurements of drugs in human hair has mainly been derived from the analytical variation. However, in hair analysis several other sources of uncertainty will contribute to the total uncertainty. Particularly, in segmental hair analysis pre-analytical variations associated with the sampling and segmentation may be significant factors in the assessment of the total uncertainty budget. The aim of this study was to develop and validate a method for the analysis of 31 common drugs in hair using ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with focus on the assessment of both the analytical and pre-analytical sampling variations. The validated method was specific, accurate (80-120%), and precise (CV≤20%) across a wide linear concentration range from 0.025-25 ng/mg for most compounds. The analytical variation was estimated to be less than 15% for almost all compounds. The method was successfully applied to 25 segmented hair specimens from deceased drug addicts showing a broad pattern of poly-drug use. The pre-analytical sampling variation was estimated from the genuine duplicate measurements of two bundles of hair collected from each subject after subtraction of the analytical component. For the most frequently detected analytes, the pre-analytical variation was estimated to be 26-69%. Thus, the pre-analytical variation was 3-7 folds larger than the analytical variation (7-13%) and hence the dominant component in the total variation (29-70%). The present study demonstrated the importance of including the pre-analytical variation in the assessment of the total uncertainty budget and in the setting of the 95%-uncertainty interval (±2CVT). Excluding the pre-analytical sampling variation could significantly affect the interpretation of results from segmental hair analysis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The use of biospecimens in population-based research: a review of the National Cancer Institute's Division of Cancer Control and Population Sciences grant portfolio.

PubMed

Carrick, Danielle M; Mette, Eliza; Hoyle, Brittany; Rogers, Scott D; Gillanders, Elizabeth M; Schully, Sheri D; Mechanic, Leah E

2014-08-01

Over the past two decades, researchers have increasingly used human biospecimens to evaluate hypotheses related to disease risk, outcomes and treatment. We conducted an analysis of population-science cancer research grants funded by the National Cancer Institute (NCI) to gain a more comprehensive understanding of biospecimens and common derivatives involved in those studies and identify opportunities for advancing the field. Data available for 1,018 extramural, peer-reviewed grants (active as of July 2012) supported by the Division of Cancer Control and Population Sciences (DCCPS), the NCI Division that supports cancer control and population-science extramural research grants, were analyzed. 455 of the grants were determined to involve biospecimens or derivatives. The most common specimen types included were whole blood (51% of grants), serum or plasma (40%), tissue (39%), and the biospecimen derivative, DNA (66%). While use of biospecimens in molecular epidemiology has become common, biospecimens for behavioral and social research is emerging, as observed in our analysis. Additionally, we found the majority of grants were using already existing biospecimens (63%). Grants that involved use of existing biospecimens resulted in lower costs (studies that used existing serum/plasma biospecimens were 4.2 times less expensive) and more publications per year (1.4 times) than grants collecting new biospecimens. This analysis serves as a first step at understanding the types of biospecimen collections supported by NCI DCCPS. There is room to encourage increased use of archived biospecimens and new collections of rarer specimen and cancer types, as well as for behavioral and social research. To facilitate these efforts, we are working to better catalogue our funded resources and make that data available to the extramural community.

Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability.

PubMed

Szulc, P; Naylor, K; Hoyle, N R; Eastell, R; Leary, E T

2017-09-01

The National Bone Health Alliance (NBHA) recommends standardized sample handling and patient preparation for C-terminal telopeptide of type I collagen (CTX-I) and N-terminal propeptide of type I procollagen (PINP) measurements to reduce pre-analytical variability. Controllable and uncontrollable patient-related factors are reviewed to facilitate interpretation and minimize pre-analytical variability. The IOF and the International Federation of Clinical Chemistry (IFCC) Bone Marker Standards Working Group have identified PINP and CTX-I in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA Bone Turnover Marker Project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation. Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection. Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation. Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.

Biospecimen User Fees: Global Feedback on a Calculator Tool.

PubMed

Matzke, Lise A M; Babinszky, Sindy; Slotty, Alex; Meredith, Anna; Castillo-Pelayo, Tania; Henderson, Marianne K; Simeon-Dubach, Daniel; Schacter, Brent; Watson, Peter H

2017-02-01

The notion of attributing user fees to researchers for biospecimens provided by biobanks has been discussed frequently in the literature. However, the considerations around how to attribute the cost for these biospecimens and data have, until recently, not been well described. Common across most biobank disciplines are similar factors that influence user fees such as capital and operating costs, internal and external demand, and market competition. A biospecimen user fee calculator tool developed by CTRNet, a tumor biobank network, was published in 2014 and is accessible online at www.biobanking.org . The next year a survey was launched that tested the applicability of this user fee tool among a global health research biobank user base, including both cancer and noncancer biobanking. Participants were first asked to estimate user fee pricing for three hypothetical user scenarios based on their biobanking experience (estimated pricing) and then to calculate fees for the same scenarios using the calculator tool (calculated pricing). Results demonstrated variation in estimated pricing that was reduced by calculated pricing. These results are similar to those found in a similar previous study restricted to a group of Canadian tumor biobanks. We conclude that the use of a biospecimen user fee calculator contributes to reduced variation of user fees and for biobank groups (e.g., biobank networks), could become an important part of a harmonization strategy.

Biospecimen User Fees: Global Feedback on a Calculator Tool

PubMed Central

Babinszky, Sindy; Slotty, Alex; Meredith, Anna; Castillo-Pelayo, Tania; Henderson, Marianne K.; Simeon-Dubach, Daniel; Schacter, Brent; Watson, Peter H.

2017-01-01

The notion of attributing user fees to researchers for biospecimens provided by biobanks has been discussed frequently in the literature. However, the considerations around how to attribute the cost for these biospecimens and data have, until recently, not been well described. Common across most biobank disciplines are similar factors that influence user fees such as capital and operating costs, internal and external demand, and market competition. A biospecimen user fee calculator tool developed by CTRNet, a tumor biobank network, was published in 2014 and is accessible online at www.biobanking.org. The next year a survey was launched that tested the applicability of this user fee tool among a global health research biobank user base, including both cancer and noncancer biobanking. Participants were first asked to estimate user fee pricing for three hypothetical user scenarios based on their biobanking experience (estimated pricing) and then to calculate fees for the same scenarios using the calculator tool (calculated pricing). Results demonstrated variation in estimated pricing that was reduced by calculated pricing. These results are similar to those found in a similar previous study restricted to a group of Canadian tumor biobanks. We conclude that the use of a biospecimen user fee calculator contributes to reduced variation of user fees and for biobank groups (e.g., biobank networks), could become an important part of a harmonization strategy. PMID:27576065

Bias due to Preanalytical Dilution of Rodent Serum for Biochemical Analysis on the Siemens Dimension Xpand Plus

PubMed Central

Johns, Jennifer L.; Moorhead, Kaitlin A.; Hu, Jing; Moorhead, Roberta C.

2018-01-01

Clinical pathology testing of rodents is often challenging due to insufficient sample volume. One solution in clinical veterinary and exploratory research environments is dilution of samples prior to analysis. However, published information on the impact of preanalytical sample dilution on rodent biochemical data is incomplete. The objective of this study was to evaluate the effects of preanalytical sample dilution on biochemical analysis of mouse and rat serum samples utilizing the Siemens Dimension Xpand Plus. Rats were obtained from end of study research projects. Mice were obtained from sentinel testing programs. For both, whole blood was collected via terminal cardiocentesis into empty tubes and serum was harvested. Biochemical parameters were measured on fresh and thawed frozen samples run straight and at dilution factors 2–10. Dilutions were performed manually, utilizing either ultrapure water or enzyme diluent per manufacturer recommendations. All diluted samples were generated directly from the undiluted sample. Preanalytical dilution caused clinically unacceptable bias in most analytes at dilution factors four and above. Dilution-induced bias in total calcium, creatinine, total bilirubin, and uric acid was considered unacceptable with any degree of dilution, based on the more conservative of two definitions of acceptability. Dilution often caused electrolyte values to fall below assay range precluding evaluation of bias. Dilution-induced bias occurred in most biochemical parameters to varying degrees and may render dilution unacceptable in the exploratory research and clinical veterinary environments. Additionally, differences between results obtained at different dilution factors may confound statistical comparisons in research settings. Comparison of data obtained at a single dilution factor is highly recommended. PMID:29497614

42 CFR 493.1249 - Standard: Preanalytic systems quality assessment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Standard: Preanalytic systems quality assessment... Nonwaived Testing Preanalytic Systems § 493.1249 Standard: Preanalytic systems quality assessment. (a) The....1241 through 493.1242. (b) The preanalytic systems quality assessment must include a review of the...

Analysis of Pre-Analytic Factors Affecting the Success of Clinical Next-Generation Sequencing of Solid Organ Malignancies.

PubMed

Chen, Hui; Luthra, Rajyalakshmi; Goswami, Rashmi S; Singh, Rajesh R; Roy-Chowdhuri, Sinchita

2015-08-28

Application of next-generation sequencing (NGS) technology to routine clinical practice has enabled characterization of personalized cancer genomes to identify patients likely to have a response to targeted therapy. The proper selection of tumor sample for downstream NGS based mutational analysis is critical to generate accurate results and to guide therapeutic intervention. However, multiple pre-analytic factors come into play in determining the success of NGS testing. In this review, we discuss pre-analytic requirements for AmpliSeq PCR-based sequencing using Ion Torrent Personal Genome Machine (PGM) (Life Technologies), a NGS sequencing platform that is often used by clinical laboratories for sequencing solid tumors because of its low input DNA requirement from formalin fixed and paraffin embedded tissue. The success of NGS mutational analysis is affected not only by the input DNA quantity but also by several other factors, including the specimen type, the DNA quality, and the tumor cellularity. Here, we review tissue requirements for solid tumor NGS based mutational analysis, including procedure types, tissue types, tumor volume and fraction, decalcification, and treatment effects.

"I don't want to be Henrietta Lacks": diverse patient perspectives on donating biospecimens for precision medicine research.

PubMed

Lee, Sandra S-J; Cho, Mildred K; Kraft, Stephanie A; Varsava, Nina; Gillespie, Katie; Ormond, Kelly E; Wilfond, Benjamin S; Magnus, David

2018-06-11

To determine whether patients distinguish between biospecimens and electronic health records (EHRs) when considering research participation to inform research protections. We conducted 20 focus groups with individuals who identified as African American, Hispanic, Chinese, South Asian, and non-Hispanic white on the collection of biospecimens and EHR data for research. Our study found that many participants did not distinguish between biospecimens and EHR data. However, some participants identified specific concerns about biospecimens. These included the need for special care and respect for biospecimens due to enduring connections between the body and identity; the potential for unacceptable future research, specifically the prospect of human cloning; heightened privacy risks; and the potential for unjust corporate profiteering. Among those who distinguished biospecimens from EHR data, many supported separate consent processes and would limit their own participation to EHR data. Considering that the potential misuse of EHR data is as great as, if not greater than, for biospecimens, more research is needed to understand how attitudes differ between biospecimens and EHR data across diverse populations. Such research should explore mechanisms beyond consent that can address diverse values, perspectives, and misconceptions about sources of patient information to build trust in research relationships.

[Quality Management and Quality Specifications of Laboratory Tests in Clinical Studies--Challenges in Pre-Analytical Processes in Clinical Laboratories].

PubMed

Ishibashi, Midori

2015-01-01

The cost, speed, and quality are the three important factors recently indicated by the Ministry of Health, Labour and Welfare (MHLW) for the purpose of accelerating clinical studies. Based on this background, the importance of laboratory tests is increasing, especially in the evaluation of clinical study participants' entry and safety, and drug efficacy. To assure the quality of laboratory tests, providing high-quality laboratory tests is mandatory. For providing adequate quality assurance in laboratory tests, quality control in the three fields of pre-analytical, analytical, and post-analytical processes is extremely important. There are, however, no detailed written requirements concerning specimen collection, handling, preparation, storage, and shipping. Most laboratory tests for clinical studies are performed onsite in a local laboratory; however, a part of laboratory tests is done in offsite central laboratories after specimen shipping. As factors affecting laboratory tests, individual and inter-individual variations are well-known. Besides these factors, standardizing the factors of specimen collection, handling, preparation, storage, and shipping, may improve and maintain the high quality of clinical studies in general. Furthermore, the analytical method, units, and reference interval are also important factors. It is concluded that, to overcome the problems derived from pre-analytical processes, it is necessary to standardize specimen handling in a broad sense.

[Research and development of medical case database: a novel medical case information system integrating with biospecimen management].

PubMed

Pan, Shiyang; Mu, Yuan; Wang, Hong; Wang, Tong; Huang, Peijun; Ma, Jianfeng; Jiang, Li; Zhang, Jie; Gu, Bing; Yi, Lujiang

2010-04-01

To meet the needs of management of medical case information and biospecimen simultaneously, we developed a novel medical case information system integrating with biospecimen management. The database established by MS SQL Server 2000 covered, basic information, clinical diagnosis, imaging diagnosis, pathological diagnosis and clinical treatment of patient; physicochemical property, inventory management and laboratory analysis of biospecimen; users log and data maintenance. The client application developed by Visual C++ 6.0 was used to implement medical case and biospecimen management, which was based on Client/Server model. This system can perform input, browse, inquest, summary of case and related biospecimen information, and can automatically synthesize case-records based on the database. Management of not only a long-term follow-up on individual, but also of grouped cases organized according to the aim of research can be achieved by the system. This system can improve the efficiency and quality of clinical researches while biospecimens are used coordinately. It realizes synthesized and dynamic management of medical case and biospecimen, which may be considered as a new management platform.

Evolutionary concepts in biobanking - the BC BioLibrary

PubMed Central

2009-01-01

Background Medical research to improve health care faces a major problem in the relatively limited availability of adequately annotated and collected biospecimens. This limitation is creating a growing gap between the pace of scientific advances and successful exploitation of this knowledge. Biobanks are an important conduit for transfer of biospecimens (tissues, blood, body fluids) and related health data to research. They have evolved outside of the historical source of tissue biospecimens, clinical pathology archives. Research biobanks have developed advanced standards, protocols, databases, and mechanisms to interface with researchers seeking biospecimens. However, biobanks are often limited in their capacity and ability to ensure quality in the face of increasing demand. Our strategy to enhance both capacity and quality in research biobanking is to create a new framework that repatriates the activity of biospecimen accrual for biobanks to clinical pathology. Methods The British Columbia (BC) BioLibrary is a framework to maximize the accrual of high-quality, annotated biospecimens into biobanks. The BC BioLibrary design primarily encompasses: 1) specialized biospecimen collection units embedded within clinical pathology and linked to a biospecimen distribution system that serves biobanks; 2) a systematic process to connect potential donors with biobanks, and to connect biobanks with consented biospecimens; and 3) interdisciplinary governance and oversight informed by public opinion. Results The BC BioLibrary has been embraced by biobanking leaders and translational researchers throughout BC, across multiple health authorities, institutions, and disciplines. An initial pilot network of three Biospecimen Collection Units has been successfully established. In addition, two public deliberation events have been held to obtain input from the public on the BioLibrary and on issues including consent, collection of biospecimens and governance. Conclusion The BC BioLibrary framework addresses common issues for clinical pathology, biobanking, and translational research across multiple institutions and clinical and research domains. We anticipate that our framework will lead to enhanced biospecimen accrual capacity and quality, reduced competition between biobanks, and a transparent process for donors that enhances public trust in biobanking. PMID:19909513

Effects of pre-analytical variables on flow cytometric diagnosis of canine lymphoma: A retrospective study (2009-2015).

PubMed

Comazzi, S; Cozzi, M; Bernardi, S; Zanella, D R; Aresu, L; Stefanello, D; Marconato, L; Martini, V

2018-02-01

Flow cytometry (FC) is increasingly being used for immunophenotyping and staging of canine lymphoma. The aim of this retrospective study was to assess pre-analytical variables that might influence the diagnostic utility of FC of lymph node (LN) fine needle aspirate (FNA) specimens from dogs with lymphoproliferative diseases. The study included 987 cases with LN FNA specimens sent for immunophenotyping that were submitted to a diagnostic laboratory in Italy from 2009 to 2015. Cases were grouped into 'diagnostic' and 'non-diagnostic'. Pre-analytical factors analysed by univariate and multivariate analyses were animal-related factors (breed, age, sex, size), operator-related factors (year, season, shipping method, submitting veterinarian) and sample-related factors (type of sample material, cellular concentration, cytological smears, artefacts). The submitting veterinarian, sample material, sample cellularity and artefacts affected the likelihood of having a diagnostic sample. The availability of specimens from different sites and of cytological smears increased the odds of obtaining a diagnostic result. Major artefacts affecting diagnostic utility included poor cellularity and the presence of dead cells. Flow cytometry on LN FNA samples yielded conclusive results in more than 90% of cases with adequate sample quality and sampling conditions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Monitoring and reporting of preanalytical errors in laboratory medicine: the UK situation.

PubMed

Cornes, Michael P; Atherton, Jennifer; Pourmahram, Ghazaleh; Borthwick, Hazel; Kyle, Betty; West, Jamie; Costelloe, Seán J

2016-03-01

Most errors in the clinical laboratory occur in the preanalytical phase. This study aimed to comprehensively describe the prevalence and nature of preanalytical quality monitoring practices in UK clinical laboratories. A survey was sent on behalf of the Association for Clinical Biochemistry and Laboratory Medicine Preanalytical Working Group (ACB-WG-PA) to all heads of department of clinical laboratories in the UK. The survey captured data on the analytical platform and Laboratory Information Management System in use; which preanalytical errors were recorded and how they were classified and gauged interest in an external quality assurance scheme for preanalytical errors. Of the 157 laboratories asked to participate, responses were received from 104 (66.2%). Laboratory error rates were recorded per number of specimens, rather than per number of requests in 51% of respondents. Aside from serum indices for haemolysis, icterus and lipaemia, which were measured in 80% of laboratories, the most common errors recorded were booking-in errors (70.1%) and sample mislabelling (56.9%) in laboratories who record preanalytical errors. Of the laboratories surveyed, 95.9% expressed an interest in guidance on recording preanalytical error and 91.8% expressed interest in an external quality assurance scheme. This survey observes a wide variation in the definition, repertoire and collection methods for preanalytical errors in the UK. Data indicate there is a lot of interest in improving preanalytical data collection. The ACB-WG-PA aims to produce guidance and support for laboratories to standardize preanalytical data collection and to help establish and validate an external quality assurance scheme for interlaboratory comparison. © The Author(s) 2015.

A Community-Driven Intervention for Improving Biospecimen Donation in African American Communities.

PubMed

Patel, Kushal; Inman, Wendelyn; Gishe, Jemal; Johnson, Owen; Brown, Elizabeth; Kanu, Mohamed; Theriot, Rosemary; Sanderson, Maureen; Hull, Pamela; Hargreaves, Margaret

2018-02-01

Human biospecimens are an invaluable resource for addressing cancers and other chronic diseases. The purpose of this study was to assess the impact of an educational intervention on biospecimen knowledge and attitudes. The participants consisted of 112 African Americans, 18 years and older, and who had not provided biospecimens for any health-related research in the past. A total of 55 participants received the educational brochure, and 57 received the educational video. The main outcomes of the study were knowledge and attitudes for biospecimen donation. This information was collected pre- and post-intervention. The average knowledge scores increased (p < 0.0001) and the average attitude scores for biospecimen donation improved (p < 0.0001) post-intervention for both the video and brochure conditions. There was an interaction between the intervention condition and knowledge where the participants who received the educational video showed a greater increase in knowledge pre-to-post compared to those who received the educational brochure (p = 0.0061). There were no significant interactions between the two intervention conditions for attitudes toward biospecimen donation. The results of this study demonstrated the feasibility and efficacy of an academic institution collaborating with the African American community in developing educational tools for biospecimen donation.

Multivariate two-part statistics for analysis of correlated mass spectrometry data from multiple biological specimens.

PubMed

Taylor, Sandra L; Ruhaak, L Renee; Weiss, Robert H; Kelly, Karen; Kim, Kyoungmi

2017-01-01

High through-put mass spectrometry (MS) is now being used to profile small molecular compounds across multiple biological sample types from the same subjects with the goal of leveraging information across biospecimens. Multivariate statistical methods that combine information from all biospecimens could be more powerful than the usual univariate analyses. However, missing values are common in MS data and imputation can impact between-biospecimen correlation and multivariate analysis results. We propose two multivariate two-part statistics that accommodate missing values and combine data from all biospecimens to identify differentially regulated compounds. Statistical significance is determined using a multivariate permutation null distribution. Relative to univariate tests, the multivariate procedures detected more significant compounds in three biological datasets. In a simulation study, we showed that multi-biospecimen testing procedures were more powerful than single-biospecimen methods when compounds are differentially regulated in multiple biospecimens but univariate methods can be more powerful if compounds are differentially regulated in only one biospecimen. We provide R functions to implement and illustrate our method as supplementary information CONTACT: sltaylor@ucdavis.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Improving preanalytic processes using the principles of lean production (Toyota Production System).

PubMed

Persoon, Thomas J; Zaleski, Sue; Frerichs, Janice

2006-01-01

The basic technologies used in preanalytic processes for chemistry tests have been mature for a long time, and improvements in preanalytic processes have lagged behind improvements in analytic and postanalytic processes. We describe our successful efforts to improve chemistry test turnaround time from a central laboratory by improving preanalytic processes, using existing resources and the principles of lean production. Our goal is to report 80% of chemistry tests in less than 1 hour and to no longer recognize a distinction between expedited and routine testing. We used principles of lean production (the Toyota Production System) to redesign preanalytic processes. The redesigned preanalytic process has fewer steps and uses 1-piece flow to move blood samples through the accessioning, centrifugation, and aliquoting processes. Median preanalytic processing time was reduced from 29 to 19 minutes, and the laboratory met the goal of reporting 80% of chemistry results in less than 1 hour for 11 consecutive months.

The Biobanking Analysis Resource Catalogue (BARCdb): a new research tool for the analysis of biobank samples

PubMed Central

Galli, Joakim; Oelrich, Johan; Taussig, Michael J.; Andreasson, Ulrika; Ortega-Paino, Eva; Landegren, Ulf

2015-01-01

We report the development of a new database of technology services and products for analysis of biobank samples in biomedical research. BARCdb, the Biobanking Analysis Resource Catalogue (http://www.barcdb.org), is a freely available web resource, listing expertise and molecular resource capabilities of research centres and biotechnology companies. The database is designed for researchers who require information on how to make best use of valuable biospecimens from biobanks and other sample collections, focusing on the choice of analytical techniques and the demands they make on the type of samples, pre-analytical sample preparation and amounts needed. BARCdb has been developed as part of the Swedish biobanking infrastructure (BBMRI.se), but now welcomes submissions from service providers throughout Europe. BARCdb can help match resource providers with potential users, stimulating transnational collaborations and ensuring compatibility of results from different labs. It can promote a more optimal use of European resources in general, both with respect to standard and more experimental technologies, as well as for valuable biobank samples. This article describes how information on service and reagent providers of relevant technologies is made available on BARCdb, and how this resource may contribute to strengthening biomedical research in academia and in the biotechnology and pharmaceutical industries. PMID:25336620

Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability.

PubMed

Fourier, Anthony; Portelius, Erik; Zetterberg, Henrik; Blennow, Kaj; Quadrio, Isabelle; Perret-Liaudet, Armand

2015-09-20

A panel of cerebrospinal fluid (CSF) biomarkers including total Tau (t-Tau), phosphorylated Tau protein at residue 181 (p-Tau) and β-amyloid peptides (Aβ42 and Aβ40), is frequently used as an aid in Alzheimer's disease (AD) diagnosis for young patients with cognitive impairment, for predicting prodromal AD in mild cognitive impairment (MCI) subjects, for AD discrimination in atypical clinical phenotypes and for inclusion/exclusion and stratification of patients in clinical trials. Due to variability in absolute levels between laboratories, there is no consensus on medical cut-off value for the CSF AD signature. Thus, for full implementation of this core AD biomarker panel in clinical routine, this issue has to be solved. Variability can be explained both by pre-analytical and analytical factors. For example, the plastic tubes used for CSF collection and storage, the lack of reference material and the variability of the analytical protocols were identified as important sources of variability. The aim of this review is to highlight these pre-analytical and analytical factors and describe efforts done to counteract them in order to establish cut-off values for core CSF AD biomarkers. This review will give the current state of recommendations. Copyright © 2015. Published by Elsevier B.V.

Impact of a biospecimen collection seminar on willingness to donate biospecimens among Chinese Americans: results from a randomized, controlled community-based trial.

PubMed

Tong, Elisa K; Fung, Lei-Chun; Stewart, Susan L; Paterniti, Debora A; Dang, Julie H T; Chen, Moon S

2014-03-01

Biospecimen collection from diverse populations can advance cancer disparities research, but is currently underrepresented. We partnered with a community-based clinic serving Cantonese-speaking Chinese Americans to develop and revise an educational seminar on biospecimen collection. Through a randomized controlled trial (n = 395), the intervention seminar was compared with a control seminar (cancer prevention) on change in willingness to donate biospecimens. At baseline, many were willing to donate a biospecimen (saliva, urine, hair, toenails, blood, unused cancerous tissue) whether healthy or hypothetically had cancer. Also, many would donate because future generations would benefit, and few had concerns about donation. In logistic regression analyses, there was an intervention effect for willingness to donate: urine if had cancer [OR, 2.2; 95% confidence interval (CI), 1.3-3.7], toenails if healthy (OR, 2.1; 95% CI, 1.4-3.2) or had cancer (OR, 2.3; 95% CI, 2.0-2.7), hair if healthy (OR, 1.8; 95% CI, 1.3-2.5) or had cancer (OR, 2.8; 95% CI, 1.9-4.0), and unused cancerous tissue (OR, 1.8; 95% CI, 1.2-2.9). There was also an intervention effect for donating because future generations would benefit (OR, 2.0; 95% CI, 1.4-3.0), and this attitude was a strong independent predictor for willingness to donate all biospecimens, whether healthy or had cancer (OR, 2.9-4.2). Cantonese-speaking Chinese American participants of an educational seminar on biospecimen collection showed greater increases in willingness to donate biospecimens and donating for the benefit of future generations, than participants who attended a control seminar. Donating for the benefit of future generations is a theme that should be incorporated in messages that encourage biospecimen donation for Chinese Americans. ©2014 AACR.

Impact of a Biospecimen Collection Seminar on Willingness to Donate Biospecimens among Chinese Americans: Results from a Randomized, Controlled Community-Based Trial

PubMed Central

Tong, Elisa K.; Fung, Lei-Chun; Stewart, Susan L.; Paterniti, Debora A.; Dang, Julie H.T.; Chen, Moon S.

2014-01-01

Background Biospecimen collection from diverse populations can advance cancer disparities research, but is currently underrepresented. Methods We partnered with a community-based clinic serving Cantonese-speaking Chinese Americans to develop and revise an educational seminar on biospecimen collection. Through a randomized controlled trial (n = 395), the intervention seminar was compared with a control seminar (cancer prevention) on change in willingness to donate biospecimens. Results At baseline, many were willing to donate a biospecimen (saliva, urine, hair, toenails, blood, unused cancerous tissue) whether healthy or hypothetically had cancer. Also, many would donate because future generations would benefit, and few had concerns about donation. In logistic regression analyses, there was an intervention effect for willingness to donate: urine if had cancer [OR, 2.2; 95% confidence interval (CI), 1.3–3.7], toenails if healthy (OR, 2.1; 95% CI, 1.4–3.2) or had cancer (OR, 2.3; 95% CI, 2.0–2.7), hair if healthy (OR, 1.8; 95% CI, 1.3–2.5) or had cancer (OR, 2.8; 95% CI, 1.9–4.0), and unused cancerous tissue (OR, 1.8; 95% CI, 1.2–2.9). There was also an intervention effect for donating because future generations would benefit (OR, 2.0; 95% CI, 1.4–3.0), and this attitude was a strong independent predictor for willingness to donate all biospecimens, whether healthy or had cancer (OR, 2.9–4.2). Conclusion Cantonese-speaking Chinese American participants of an educational seminar on biospecimen collection showed greater increases in willingness to donate biospecimens and donating for the benefit of future generations, than participants who attended a control seminar. Impact Donating for the benefit of future generations is a theme that should be incorporated in messages that encourage biospecimen donation for Chinese Americans. PMID:24609848

Application Period Open for NCI Biospecimen Use | Division of Cancer Prevention

Cancer.gov

The application period for investigators interested in obtaining biospecimens and data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial re-opened June 1. A separate application for obtaining biospecimens and data with research funding is also open. |

Assays for Qualification and Quality Stratification of Clinical Biospecimens Used in Research: A Technical Report from the ISBER Biospecimen Science Working Group.

PubMed

Betsou, Fay; Bulla, Alexandre; Cho, Sang Yun; Clements, Judith; Chuaqui, Rodrigo; Coppola, Domenico; De Souza, Yvonne; De Wilde, Annemieke; Grizzle, William; Guadagni, Fiorella; Gunter, Elaine; Heil, Stacey; Hodgkinson, Verity; Kessler, Joseph; Kiehntopf, Michael; Kim, Hee Sung; Koppandi, Iren; Shea, Katheryn; Singh, Rajeev; Sobel, Marc; Somiari, Stella; Spyropoulos, Demetri; Stone, Mars; Tybring, Gunnel; Valyi-Nagy, Klara; Van den Eynden, Gert; Wadhwa, Lalita

2016-10-01

This technical report presents quality control (QC) assays that can be performed in order to qualify clinical biospecimens that have been biobanked for use in research. Some QC assays are specific to a disease area. Some QC assays are specific to a particular downstream analytical platform. When such a qualification is not possible, QC assays are presented that can be performed to stratify clinical biospecimens according to their biomolecular quality.

Assays for Qualification and Quality Stratification of Clinical Biospecimens Used in Research: A Technical Report from the ISBER Biospecimen Science Working Group

PubMed Central

Bulla, Alexandre; Cho, Sang Yun; Clements, Judith; Chuaqui, Rodrigo; Coppola, Domenico; De Souza, Yvonne; De Wilde, Annemieke; Grizzle, William; Guadagni, Fiorella; Gunter, Elaine; Heil, Stacey; Hodgkinson, Verity; Kessler, Joseph; Kiehntopf, Michael; Kim, Hee Sung; Koppandi, Iren; Shea, Katheryn; Singh, Rajeev; Sobel, Marc; Somiari, Stella; Spyropoulos, Demetri; Stone, Mars; Tybring, Gunnel; Valyi-Nagy, Klara; Van den Eynden, Gert; Wadhwa, Lalita

2016-01-01

This technical report presents quality control (QC) assays that can be performed in order to qualify clinical biospecimens that have been biobanked for use in research. Some QC assays are specific to a disease area. Some QC assays are specific to a particular downstream analytical platform. When such a qualification is not possible, QC assays are presented that can be performed to stratify clinical biospecimens according to their biomolecular quality. PMID:27046294

Ten years of preanalytical monitoring and control: Synthetic Balanced Score Card Indicator

PubMed Central

López-Garrigós, Maite; Flores, Emilio; Santo-Quiles, Ana; Gutierrez, Mercedes; Lugo, Javier; Lillo, Rosa; Leiva-Salinas, Carlos

2015-01-01

Introduction Preanalytical control and monitoring continue to be an important issue for clinical laboratory professionals. The aim of the study was to evaluate a monitoring system of preanalytical errors regarding not suitable samples for analysis, based on different indicators; to compare such indicators in different phlebotomy centres; and finally to evaluate a single synthetic preanalytical indicator that may be included in the balanced scorecard management system (BSC). Materials and methods We collected individual and global preanalytical errors in haematology, coagulation, chemistry, and urine samples analysis. We also analyzed a synthetic indicator that represents the sum of all types of preanalytical errors, expressed in a sigma level. We studied the evolution of those indicators over time and compared indicator results by way of the comparison of proportions and Chi-square. Results There was a decrease in the number of errors along the years (P < 0.001). This pattern was confirmed in primary care patients, inpatients and outpatients. In blood samples, fewer errors occurred in outpatients, followed by inpatients. Conclusion We present a practical and effective methodology to monitor unsuitable sample preanalytical errors. The synthetic indicator results summarize overall preanalytical sample errors, and can be used as part of BSC management system. PMID:25672466

A survey of patient perspectives on the research use of health information and biospecimens.

PubMed

Page, Stacey A; Manhas, Kiran Pohar; Muruve, Daniel A

2016-08-15

Personal health information and biospecimens are valuable research resources essential for the advancement of medicine and protected by national standards and provincial statutes. Research ethics and privacy standards attempt to balance individual interests with societal interests. However these standards may not reflect public opinion or preferences. The purpose of this study was to assess the opinions and preferences of patients with kidney disease about the use of their health information and biospecimens for medical research. A 45-item survey was distributed to a convenience sample of patients at an outpatient clinic in a large urban centre. The survey briefly addressed sociodemographic and illness characteristics. Opinions were sought on the research use of health information and biospecimens including consent preferences. Two hundred eleven of 400 distributed surveys were completed (response rate 52.8 %). Respondents were generally supportive of medical research and trusting of researchers. Many respondents supported the use of their information and biospecimens for health research and also preferred consent be sought for use of health information and biospecimens. Some supported the use of their information and biospecimens for research without consent. There were significant differences in the opinions people offered regarding the research use of biospecimens compared to health information. Some respondent perspectives about consent were at odds with current regulatory and legal standards. Clinical health data and biospecimens are valuable research resources, critical to the advancement of medicine. Use of these data for research requires balancing respect for individual autonomy, privacy and the societal interest in the greater good. Incongruence between some respondent perspectives and the regulatory standards suggest both a need for public education and review of legislation to increase understanding and ensure the public's trust is maintained.

Generation and validation of a universal perinatal database and biospecimen repository: PeriBank.

PubMed

Antony, K M; Hemarajata, P; Chen, J; Morris, J; Cook, C; Masalas, D; Gedminas, M; Brown, A; Versalovic, J; Aagaard, K

2016-11-01

There is a dearth of biospecimen repositories available to perinatal researchers. In order to address this need, here we describe the methodology used to establish such a resource. With the collaboration of MedSci.net, we generated an online perinatal database with 847 fields of clinical information. Simultaneously, we established a biospecimen repository of the same clinical participants. The demographic and clinical outcomes data are described for the first 10 000 participants enrolled. The demographic characteristics are consistent with the demographics of the delivery hospitals. Quality analysis of the biospecimens reveals variation in very few analytes. Furthermore, since the creation of PeriBank, we have demonstrated validity of the database and tissue integrity of the biospecimen repository. Here we establish that the creation of a universal perinatal database and biospecimen collection is not only possible, but allows for the performance of state-of-the-science translational perinatal research and is a potentially valuable resource to academic perinatal researchers.

International Childhood Cancer Cohort Consortium

Cancer.gov

An alliance of several large-scale prospective cohort studies of children to pool data and biospecimens from individual cohorts to study various modifiable and genetic factors in relation to cancer risk

New Funding Opportunity: Biospecimen Core Resource | Office of Cancer Clinical Proteomics Research

Cancer.gov

The purpose of this notice is to notify the community that the National Cancer Institute's (NCI’s) Office of Cancer Clinical Proteomics Research (OCCPR) is seeking sources to establish a Biospecimen Core Resource (BCR), capable of receiving, qualifying, processing, and distributing annotated biospecimens.

Quality Measures in Pre-Analytical Phase of Tissue Processing: Understanding Its Value in Histopathology.

PubMed

Rao, Shalinee; Masilamani, Suresh; Sundaram, Sandhya; Duvuru, Prathiba; Swaminathan, Rajendiran

2016-01-01

Quality monitoring in histopathology unit is categorized into three phases, pre-analytical, analytical and post-analytical, to cover various steps in the entire test cycle. Review of literature on quality evaluation studies pertaining to histopathology revealed that earlier reports were mainly focused on analytical aspects with limited studies on assessment of pre-analytical phase. Pre-analytical phase encompasses several processing steps and handling of specimen/sample by multiple individuals, thus allowing enough scope for errors. Due to its critical nature and limited studies in the past to assess quality in pre-analytical phase, it deserves more attention. This study was undertaken to analyse and assess the quality parameters in pre-analytical phase in a histopathology laboratory. This was a retrospective study done on pre-analytical parameters in histopathology laboratory of a tertiary care centre on 18,626 tissue specimens received in 34 months. Registers and records were checked for efficiency and errors for pre-analytical quality variables: specimen identification, specimen in appropriate fixatives, lost specimens, daily internal quality control performance on staining, performance in inter-laboratory quality assessment program {External quality assurance program (EQAS)} and evaluation of internal non-conformities (NC) for other errors. The study revealed incorrect specimen labelling in 0.04%, 0.01% and 0.01% in 2007, 2008 and 2009 respectively. About 0.04%, 0.07% and 0.18% specimens were not sent in fixatives in 2007, 2008 and 2009 respectively. There was no incidence of specimen lost. A total of 113 non-conformities were identified out of which 92.9% belonged to the pre-analytical phase. The predominant NC (any deviation from normal standard which may generate an error and result in compromising with quality standards) identified was wrong labelling of slides. Performance in EQAS for pre-analytical phase was satisfactory in 6 of 9 cycles. A low incidence of errors in pre-analytical phase implies that a satisfactory level of quality standards was being practiced with still scope for improvement.

Preanalytical requirements of urinalysis

PubMed Central

Delanghe, Joris; Speeckaert, Marijn

2014-01-01

Urine may be a waste product, but it contains an enormous amount of information. Well-standardized procedures for collection, transport, sample preparation and analysis should become the basis of an effective diagnostic strategy for urinalysis. As reproducibility of urinalysis has been greatly improved due to recent technological progress, preanalytical requirements of urinalysis have gained importance and have become stricter. Since the patients themselves often sample urine specimens, urinalysis is very susceptible to preanalytical issues. Various sampling methods and inappropriate specimen transport can cause important preanalytical errors. The use of preservatives may be helpful for particular analytes. Unfortunately, a universal preservative that allows a complete urinalysis does not (yet) exist. The preanalytical aspects are also of major importance for newer applications (e.g. metabolomics). The present review deals with the current preanalytical problems and requirements for the most common urinary analytes. PMID:24627718

How to conduct External Quality Assessment Schemes for the pre-analytical phase?

PubMed

Kristensen, Gunn B B; Aakre, Kristin Moberg; Kristoffersen, Ann Helen; Sandberg, Sverre

2014-01-01

In laboratory medicine, several studies have described the most frequent errors in the different phases of the total testing process, and a large proportion of these errors occur in the pre-analytical phase. Schemes for registration of errors and subsequent feedback to the participants have been conducted for decades concerning the analytical phase by External Quality Assessment (EQA) organizations operating in most countries. The aim of the paper is to present an overview of different types of EQA schemes for the pre-analytical phase, and give examples of some existing schemes. So far, very few EQA organizations have focused on the pre-analytical phase, and most EQA organizations do not offer pre-analytical EQA schemes (EQAS). It is more difficult to perform and standardize pre-analytical EQAS and also, accreditation bodies do not ask the laboratories for results from such schemes. However, some ongoing EQA programs for the pre-analytical phase do exist, and some examples are given in this paper. The methods used can be divided into three different types; collecting information about pre-analytical laboratory procedures, circulating real samples to collect information about interferences that might affect the measurement procedure, or register actual laboratory errors and relate these to quality indicators. These three types have different focus and different challenges regarding implementation, and a combination of the three is probably necessary to be able to detect and monitor the wide range of errors occurring in the pre-analytical phase.

Preanalytics in lung cancer.

PubMed

Warth, Arne; Muley, Thomas; Meister, Michael; Weichert, Wilko

2015-01-01

Preanalytic sampling techniques and preparation of tissue specimens strongly influence analytical results in lung tissue diagnostics both on the morphological but also on the molecular level. However, in contrast to analytics where tremendous achievements in the last decade have led to a whole new portfolio of test methods, developments in preanalytics have been minimal. This is specifically unfortunate in lung cancer, where usually only small amounts of tissue are at hand and optimization in all processing steps is mandatory in order to increase the diagnostic yield. In the following, we provide a comprehensive overview on some aspects of preanalytics in lung cancer from the method of sampling over tissue processing to its impact on analytical test results. We specifically discuss the role of preanalytics in novel technologies like next-generation sequencing and in the state-of the-art cytology preparations. In addition, we point out specific problems in preanalytics which hamper further developments in the field of lung tissue diagnostics.

A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project.

PubMed

Carithers, Latarsha J; Ardlie, Kristin; Barcus, Mary; Branton, Philip A; Britton, Angela; Buia, Stephen A; Compton, Carolyn C; DeLuca, David S; Peter-Demchok, Joanne; Gelfand, Ellen T; Guan, Ping; Korzeniewski, Greg E; Lockhart, Nicole C; Rabiner, Chana A; Rao, Abhi K; Robinson, Karna L; Roche, Nancy V; Sawyer, Sherilyn J; Segrè, Ayellet V; Shive, Charles E; Smith, Anna M; Sobin, Leslie H; Undale, Anita H; Valentino, Kimberly M; Vaught, Jim; Young, Taylor R; Moore, Helen M

2015-10-01

The Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project. Other research projects can follow this model and form beneficial partnerships with rapid autopsy and organ procurement organizations to collect high quality biospecimens and associated clinical data for genomic studies. Biospecimens, clinical and genomic data, and Standard Operating Procedures guiding biospecimen collection for the GTEx project are available to the research community.

Barriers and strategies to participation in tissue research among African-American men

PubMed Central

Boyd, Danielle; Carter, Kimberly; Gehlert, Sarah; Thompson, Vetta Sanders

2015-01-01

Before the burgeoning field of biospecimen collection can advance prevention and treatment methods, researchers must access diverse molecular data samples. However minorities, especially African American men, remain reticent to join these studies. This study, using theory based approaches, investigated African American men’s barriers to participating in biorepository research. Fourteen focus groups were conducted among 70 African American men (ages 40 to 80). The groups were stratified by prostate cancer history and educational attainment background. Participants identified perceived factors that promoted or hindered study participation when questioned about their knowledge and attitudes about biospecimen research. Ninety-four percent of participants indicated never participating in a study that collected biological samples. Barriers to their participation included lack of knowledge and understanding regarding biospecimen research practices and uses. In addition they extensively cited a prevalent mistrust of the medical community and discomfort with study recruitment practices. African American males were more willing to participate in biorepository studies with physician endorsement or if they understood that participation could benefit future generations. Men also wanted more recruitment and advertising done in familiar places. PMID:26341221

42 CFR 493.1240 - Condition: Preanalytic systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Preanalytic systems. 493.1240 Section 493.1240 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... of the preanalytic systems and correct identified problems as specified in § 493.1249 for each...

Drone inflight mixing of biochemical samples.

PubMed

Katariya, Mayur; Chung, Dwayne Chung Kim; Minife, Tristan; Gupta, Harshit; Zahidi, Alifa Afiah Ahmad; Liew, Oi Wah; Ng, Tuck Wah

2018-03-15

Autonomous systems for sample transport to the laboratory for analysis can be improved in terms of timeliness, cost and error mitigation in the pre-analytical testing phase. Drones have been reported for outdoor sample transport but incorporating devices on them to attain homogenous mixing of reagents during flight to enhance sample processing timeliness is limited by payload issues. It is shown here that flipping maneuvers conducted with quadcopters are able to facilitate complete and gentle mixing. This capability incorporated during automated sample transport serves to address an important factor contributing to pre-analytical variability which ultimately impacts on test result reliability. Copyright © 2018 Elsevier Inc. All rights reserved.

Multi-institutional tumor banking: lessons learned from a pancreatic cancer biospecimen repository.

PubMed

Demeure, Michael J; Sielaff, Timothy; Koep, Larry; Prinz, Richard; Moser, A James; Zeh, Herb; Hostetter, Galen; Black, Jodi; Decker, Ardis; Rosewell, Sandra; Bussey, Kimberly J; Von Hoff, Daniel

2010-10-01

Clinically annotated pancreatic cancer samples are needed for progress to be made toward developing more effective treatments for this deadly cancer. As part of a National Cancer Institute-funded program project, we established a biospecimen core to support the research efforts. This article summarizes the key hurdles encountered and solutions we found in the process of developing a successful multi-institution biospecimen repository.

To Share or Not to Share? A Survey of Biomedical Researchers in the U.S. Southwest, an Ethnically Diverse Region.

PubMed

Oushy, Mai H; Palacios, Rebecca; Holden, Alan E C; Ramirez, Amelie G; Gallion, Kipling J; O'Connell, Mary A

2015-01-01

Cancer health disparities research depends on access to biospecimens from diverse racial/ethnic populations. This multimethodological study, using mixed methods for quantitative and qualitative analysis of survey results, assessed barriers, concerns, and practices for sharing biospecimens/data among researchers working with biospecimens from minority populations in a 5 state region of the United States (Arizona, Colorado, New Mexico, Oklahoma, and Texas). The ultimate goals of this research were to understand data sharing barriers among biomedical researchers; guide strategies to increase participation in biospecimen research; and strengthen collaborative opportunities among researchers. Email invitations to anonymous participants (n = 605 individuals identified by the NIH RePORT database), resulted in 112 responses. The survey assessed demographics, specimen collection data, and attitudes about virtual biorepositories. Respondents were primarily principal investigators at PhD granting institutions (91.1%) conducting basic (62.3%) research; most were non-Hispanic White (63.4%) and men (60.6%). The low response rate limited the statistical power of the analyses, further the number of respondents for each survey question was variable. Findings from this study identified barriers to biospecimen research, including lack of access to sufficient biospecimens, and limited availability of diverse tissue samples. Many of these barriers can be attributed to poor annotation of biospecimens, and researchers' unwillingness to share existing collections. Addressing these barriers to accessing biospecimens is essential to combating cancer in general and cancer health disparities in particular. This study confirmed researchers' willingness to participate in a virtual biorepository (n = 50 respondents agreed). However, researchers in this region listed clear specifications for establishing and using such a biorepository: specifications related to standardized procedures, funding, and protections of human subjects and intellectual property. The results help guide strategies to increase data sharing behaviors and to increase participation of researchers with multiethnic biospecimen collections in collaborative research endeavors. Data sharing by researchers is essential to leveraging knowledge and resources needed for the advancement of research on cancer health disparities. Although U.S. funding entities have guidelines for data and resource sharing, future efforts should address researcher preferences in order to promote collaboration to address cancer health disparities.

Ethics Reporting in Biospecimen and Genetic Research: Current Practice and Suggestions for Changes

PubMed Central

Chin, William Wei Lim; Wieschowski, Susanne; Prokein, Jana; Illig, Thomas

2016-01-01

Modern approaches for research with human biospecimens employ a variety of substantially different types of ethics approval and informed consent. In most cases, standard ethics reporting such as “consent and approval was obtained” is no longer meaningful. A structured analysis of 120 biospecimen studies recently published in top journals revealed that more than 85% reported on consent and approval, but in more than 90% of cases, this reporting was insufficient and thus potentially misleading. Editorial policies, reporting guidelines, and material transfer agreements should include recommendations for meaningful ethics reporting in biospecimen research. Meaningful ethics reporting is possible without higher word counts and could support public trust as well as networked research. PMID:27483445

Improving quality in the preanalytical phase through innovation, on behalf of the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE).

PubMed

Lippi, Giuseppe; Baird, Geoffrey S; Banfi, Giuseppe; Bölenius, Karin; Cadamuro, Janne; Church, Stephen; Cornes, Michael P; Dacey, Anna; Guillon, Antoine; Hoffmann, Georg; Nybo, Mads; Premawardhana, Lakdasa Devananda; Salinas, María; Sandberg, Sverre; Slingerland, Robbert; Stankovic, Ana; Sverresdotter, Sylte Marit; Vermeersch, Pieter; Simundic, Ana-Maria

2017-03-01

It is now undeniable that laboratory testing is vital for the diagnosis, prognostication and therapeutic monitoring of human disease. Despite the many advances made for achieving a high degree of quality and safety in the analytical part of diagnostic testing, many hurdles in the total testing process remain, especially in the preanalytical phase ranging from test ordering to obtaining and managing the biological specimens. The Working Group for the Preanalytical Phase (WG-PRE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has planned many activities aimed at mitigating the vulnerability of the preanalytical phase, including the organization of three European meetings in the past 7 years. Hence, this collective article follows the previous three opinion papers that were published by the EFLM WGPRE on the same topic, and brings together the summaries of the presentations that will be given at the 4th EFLM-BD meeting "Improving quality in the preanalytical phase through innovation" in Amsterdam, 24-25 March, 2017.

Knowledge and Beliefs About Biospecimen Research Among Chinese Older Women in Chicago's Chinatown.

PubMed

Simon, Melissa A; Tom, Laura S; Dong, XinQi

2017-07-01

Enhancing the participation of Chinese older women in biobanking efforts is important for precision medicine efforts, as underrepresented groups risk benefiting less than others from medical advancements in individualized therapies. Focusing on a sample of Chinese older women in Chicago's Chinatown, this qualitative study seeks to describe attitudes toward, and barriers and facilitators of, participation in biospecimen research. We conducted six focus groups among Chinese-speaking adult women age 45 and above. Focus groups were transcribed, coded, and analyzed for emergent themes. Forty-seven women participated in focus groups, the majority (66.0%) were age 66 and over and half (50.1%) had less than a high school education. Participants expressed predominantly positive attitudes toward biospecimen research, but also identified multifaceted barriers to participation that included cultural beliefs of the body, perceived physical and privacy risks, as well as perceptions related to aging. Use of minimally invasive biospecimen collection and education to promote awareness of biospecimen research were suggested facilitators to increasing biospecimen research participation. Culturally and linguistically isolated populations like Chinese older women are at risk of exclusion from advancements in precision medicine. Our findings provide cultural insights for tailoring interventions for Chinese older women to increase knowledge, change attitudes, and increase intention and participation in biospecimen research. We also highlight the need for individual, family, and community level interventions to promote healthy aging among Chinese older women. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Culturally appropriate education intervention on biospecimen research participation among Chinese Americans.

PubMed

Gao, Wanzhen; Ma, Grace X; Tan, Yin; Fang, Carolyn; Weaver, Joellen; Jin, Ming; Lai, Philip; Godwin, Andrew K

2014-03-01

Chinese Americans are at increased risk for hepatitis B virus (HBV) infection. To reduce or eliminate disparities in HBV-related infection rates, participation in scientific investigations of HBV risk and treatment, including biospecimen sampling, is important. However, Asian Americans have low rates of participation in biospecimen research, and little is known about how educational interventions affect knowledge and participation in HBV-related biospecimen research. Eight Chinese community-based organizations participated in a quasi-experimental, two-group design with education assessments at pre- and postworkshop and a 3-month follow-up. Four sites were randomly assigned to receive the intervention (n = 175) and four sites to receive general health education (control; n = 240). Participant knowledge about biospecimen research increased from pre- to posteducation in the intervention but not in the control condition. Of intervention participants, 83.4% (146/175) donated one tube of blood for future HBV biospecimen research, and 50.9% (89/175) donated another tube of blood for HBV testing. In contrast, only 1.1% of participants in the control condition reported donating a blood sample at follow-up assessment. The intervention program significantly increased knowledge of and participation in HBV biospecimen research among Chinese Americans. Community-based participatory research (CBPR) methods featured active support by community leaders, a culturally specific curriculum, and convenient, immediate access to blood sampling, which resulted in high donation rates. HBV-related morbidity and mortality is an urgent problem faced by Chinese Americans. CBPR provides a model for engaging communities in early detection, vaccination, and treatment that can reduce this health threat. ©2014 AACR.

Is a pre-analytical process for urinalysis required?

PubMed

Petit, Morgane; Beaudeux, Jean-Louis; Majoux, Sandrine; Hennequin, Carole

2017-10-01

For the reliable urinary measurement of calcium, phosphate and uric acid, a pre-analytical process by adding acid or base to urine samples at laboratory is recommended in order to dissolve precipitated solutes. Several studies on different kind of samples and analysers have previously shown that a such pre-analytical treatment is useless. The objective was to study the necessity of pre-analytical treatment of urine on samples collected using the V-Monovette ® (Sarstedt) system and measured on the analyser Architect C16000 (Abbott Diagnostics). Sixty urinary samples of hospitalized patients were selected (n=30 for calcium and phosphate, and n=30 for uric acid). After acidification of urine samples for measurement of calcium and phosphate, and alkalinisation for measurement of uric acid respectively, differences between results before and after the pre-analytical treatment were compared to acceptable limits recommended by the French society of clinical biology (SFBC). No difference in concentration between before and after pre-analytical treatment of urine samples exceeded acceptable limits from SFBC for measurement of calcium and uric acid. For phosphate, only one sample exceeded these acceptable limits, showing a result paradoxically lower after acidification. In conclusion, in agreement with previous study, our results show that acidification or alkalinisation of urine samples from 24 h urines or from urination is not a pre-analytical necessity for measurement of calcium, phosphate and uric acid.

Preanalytical errors in medical laboratories: a review of the available methodologies of data collection and analysis.

PubMed

West, Jamie; Atherton, Jennifer; Costelloe, Seán J; Pourmahram, Ghazaleh; Stretton, Adam; Cornes, Michael

2017-01-01

Preanalytical errors have previously been shown to contribute a significant proportion of errors in laboratory processes and contribute to a number of patient safety risks. Accreditation against ISO 15189:2012 requires that laboratory Quality Management Systems consider the impact of preanalytical processes in areas such as the identification and control of non-conformances, continual improvement, internal audit and quality indicators. Previous studies have shown that there is a wide variation in the definition, repertoire and collection methods for preanalytical quality indicators. The International Federation of Clinical Chemistry Working Group on Laboratory Errors and Patient Safety has defined a number of quality indicators for the preanalytical stage, and the adoption of harmonized definitions will support interlaboratory comparisons and continual improvement. There are a variety of data collection methods, including audit, manual recording processes, incident reporting mechanisms and laboratory information systems. Quality management processes such as benchmarking, statistical process control, Pareto analysis and failure mode and effect analysis can be used to review data and should be incorporated into clinical governance mechanisms. In this paper, The Association for Clinical Biochemistry and Laboratory Medicine PreAnalytical Specialist Interest Group review the various data collection methods available. Our recommendation is the use of the laboratory information management systems as a recording mechanism for preanalytical errors as this provides the easiest and most standardized mechanism of data capture.

Preanalytical external quality assessment of the Croatian Society of Medical Biochemistry and Laboratory Medicine and CROQALM: finding undetected weak spots.

PubMed

Nikolac, Nora; Krleza, Jasna Lenicek; Simundic, Ana-Maria

2017-02-15

The aim of this paper is to present results of first two years of preanalytical external quality assessment (EQA) in Croatia. This paper summarizes results from 6 rounds of preanalytical EQA during 2014-2016 in 161-175 Croatian laboratories (number ranged between cycles). EQA was designed as an online survey of the compliance with National recommendations for phlebotomy (NRP). Forty-seven questions in 5 categories are analyzed (materials and equipment, patient identification, patient preparation, sampling and storage). Additionally, preanalytical cases are presented. Overall performance scores (Question score (Qscore) for compliance with NRP and Case score (Cscore) for preanalytical cases) are calculated for each question/case as a proportion of laboratories with satisfactory procedure (x 100). Qscores and Cscores ≥ 70 were classified as acceptable (maximal score = 100). In investigation of compliance with NRP, acceptable Qscores were obtained for 34/47 questions. The lowest scores were observed for the availability of sterile disposable tourniquets (Qscore = 15) and safe-sharp needles (Qscore = 34), obtaining patients address as an identifier (Qscore = 21), using glycolysis inhibitor tubes for glucose concentration measurement (Qscore = 21) and verification of manufacturers declarations on temperature and time of storage (Qscore = 31). There was no statistically significant difference in overall Qscore according to different categories of phlebotomy procedures (P = 0.284). The results of preanalytical cases showed acceptable Cscore values for all cases (89-96). First two years of preanalytical EQA showed good compliance with the NRP and excellent expertise in resolving complex preanalytical issues. Major critical spots are lack of availability of safe-sharp needles, disposable tourniquets and glucose inhibitor tubes.

Preanalytical external quality assessment of the Croatian Society of Medical Biochemistry and Laboratory Medicine and CROQALM: finding undetected weak spots

PubMed Central

Nikolac, Nora; Krleza, Jasna Lenicek; Simundic, Ana-Maria

2017-01-01

Introduction The aim of this paper is to present results of first two years of preanalytical external quality assessment (EQA) in Croatia. Materials and methods This paper summarizes results from 6 rounds of preanalytical EQA during 2014-2016 in 161-175 Croatian laboratories (number ranged between cycles). EQA was designed as an online survey of the compliance with National recommendations for phlebotomy (NRP). Forty-seven questions in 5 categories are analyzed (materials and equipment, patient identification, patient preparation, sampling and storage). Additionally, preanalytical cases are presented. Overall performance scores (Question score (Qscore) for compliance with NRP and Case score (Cscore) for preanalytical cases) are calculated for each question/case as a proportion of laboratories with satisfactory procedure (x 100). Qscores and Cscores ≥ 70 were classified as acceptable (maximal score = 100). Results In investigation of compliance with NRP, acceptable Qscores were obtained for 34/47 questions. The lowest scores were observed for the availability of sterile disposable tourniquets (Qscore = 15) and safe-sharp needles (Qscore = 34), obtaining patients address as an identifier (Qscore = 21), using glycolysis inhibitor tubes for glucose concentration measurement (Qscore = 21) and verification of manufacturers declarations on temperature and time of storage (Qscore = 31). There was no statistically significant difference in overall Qscore according to different categories of phlebotomy procedures (P = 0.284). The results of preanalytical cases showed acceptable Cscore values for all cases (89-96). Conclusion First two years of preanalytical EQA showed good compliance with the NRP and excellent expertise in resolving complex preanalytical issues. Major critical spots are lack of availability of safe-sharp needles, disposable tourniquets and glucose inhibitor tubes. PMID:28392736

To Share or Not to Share? A Survey of Biomedical Researchers in the U.S. Southwest, an Ethnically Diverse Region

PubMed Central

Oushy, Mai H.; Palacios, Rebecca; Holden, Alan E. C.; Ramirez, Amelie G.; Gallion, Kipling J.; O’Connell, Mary A.

2015-01-01

Background Cancer health disparities research depends on access to biospecimens from diverse racial/ethnic populations. This multimethodological study, using mixed methods for quantitative and qualitative analysis of survey results, assessed barriers, concerns, and practices for sharing biospecimens/data among researchers working with biospecimens from minority populations in a 5 state region of the United States (Arizona, Colorado, New Mexico, Oklahoma, and Texas). The ultimate goals of this research were to understand data sharing barriers among biomedical researchers; guide strategies to increase participation in biospecimen research; and strengthen collaborative opportunities among researchers. Methods and Population Email invitations to anonymous participants (n = 605 individuals identified by the NIH RePORT database), resulted in 112 responses. The survey assessed demographics, specimen collection data, and attitudes about virtual biorepositories. Respondents were primarily principal investigators at PhD granting institutions (91.1%) conducting basic (62.3%) research; most were non-Hispanic White (63.4%) and men (60.6%). The low response rate limited the statistical power of the analyses, further the number of respondents for each survey question was variable. Results Findings from this study identified barriers to biospecimen research, including lack of access to sufficient biospecimens, and limited availability of diverse tissue samples. Many of these barriers can be attributed to poor annotation of biospecimens, and researchers’ unwillingness to share existing collections. Addressing these barriers to accessing biospecimens is essential to combating cancer in general and cancer health disparities in particular. This study confirmed researchers’ willingness to participate in a virtual biorepository (n = 50 respondents agreed). However, researchers in this region listed clear specifications for establishing and using such a biorepository: specifications related to standardized procedures, funding, and protections of human subjects and intellectual property. The results help guide strategies to increase data sharing behaviors and to increase participation of researchers with multiethnic biospecimen collections in collaborative research endeavors Conclusions Data sharing by researchers is essential to leveraging knowledge and resources needed for the advancement of research on cancer health disparities. Although U.S. funding entities have guidelines for data and resource sharing, future efforts should address researcher preferences in order to promote collaboration to address cancer health disparities. PMID:26378445

From in vivo to in vitro: How the Guatemala STD Experiments Transformed Bodies Into Biospecimens.

PubMed

Spector-Bagdady, Kayte; Lombardo, Paul A

2018-06-01

Policy Points: While most scholarship regarding the US Public Health Service's STD experiments in Guatemala during the 1940s has focused on the intentional exposure experiments, secondary research was also conducted on biospecimens collected from these subjects. These biospecimen experiments continued after the Guatemala grant ended, and the specimens were used in conjunction with those from the Tuskegee syphilis experiments for ongoing research. We argue there should be a public accounting of whether there are still biospecimens from the Guatemala and Tuskegee experiments held in US government biorepositories today. If such specimens exist, they should be retired from US government research archives because they were collected unethically as understood at the time. The US Public Health Service's Guatemala STD experiments (1946-1948) included intentional exposure to pathogens and testing of postexposure prophylaxis methods for syphilis, gonorrhea, and chancroid in over 1,300 soldiers, commercial sex workers, prison inmates, and psychiatric patients. Though the experiments had officially ended, the biospecimens collected from these subjects continued to be used for research at least into the 1950s. We analyzed historical documents-including clinical and laboratory records, correspondence, final reports, and medical records-for information relevant to these biospecimen experiments from the US National Archives. In addition, we researched material from past governmental investigations into the Guatemala STD experiments, including those of the US Presidential Commission for the Study of Bioethical Issues and the Guatemalan Comisión Presidencial para el Esclarecimiento de los Experimentos Practicados con Humanos en Guatemala. Identified spinal fluid, blood specimens, and tissue collected during the Guatemala diagnostic methodology and intentional exposure experiments were subsequently distributed to laboratories throughout the United States for use in ongoing research until at least 1957. Five psychiatric patient subjects involved in these biospecimen experiments died soon after experimental exposure to STDs. The same US government researchers working with the Guatemala biospecimens after the exposure experiments ended were also working with specimens taken from the Tuskegee syphilis study. There should be a complete public accounting of whether biospecimens from the Guatemala and Tuskegee experiments are held in US government biorepositories today. If they still exist, these specimens should be retired from such biorepositories and their future disposition determined by stakeholders, including representatives from the communities from which they were derived. © 2018 Milbank Memorial Fund.

Preanalytical Errors in Hematology Laboratory- an Avoidable Incompetence.

PubMed

HarsimranKaur, Vikram Narang; Selhi, Pavneet Kaur; Sood, Neena; Singh, Aminder

2016-01-01

Quality assurance in the hematology laboratory is a must to ensure laboratory users of reliable test results with high degree of precision and accuracy. Even after so many advances in hematology laboratory practice, pre-analytical errors remain a challenge for practicing pathologists. This study was undertaken with an objective to evaluate the types and frequency of preanalytical errors in hematology laboratory of our center. All the samples received in the Hematology Laboratory of Dayanand Medical College and Hospital, Ludhiana, India over a period of one year (July 2013-July 2014) were included in the study and preanalytical variables like clotted samples, quantity not sufficient, wrong sample, without label, wrong label were studied. Of 471,006 samples received in the laboratory, preanalytical errors, as per the above mentioned categories was found in 1802 samples. The most common error was clotted samples (1332 samples, 0.28% of the total samples) followed by quantity not sufficient (328 sample, 0.06%), wrong sample (96 samples, 0.02%), without label (24 samples, 0.005%) and wrong label (22 samples, 0.005%). Preanalytical errors are frequent in laboratories and can be corrected by regular analysis of the variables involved. Rectification can be done by regular education of the staff.

Prevalence of Pre-Analytical Errors in Clinical Chemistry Diagnostic Labs in Sulaimani City of Iraqi Kurdistan

PubMed Central

2017-01-01

Background Laboratory testing is roughly divided into three phases: a pre-analytical phase, an analytical phase and a post-analytical phase. Most analytical errors have been attributed to the analytical phase. However, recent studies have shown that up to 70% of analytical errors reflect the pre-analytical phase. The pre-analytical phase comprises all processes from the time a laboratory request is made by a physician until the specimen is analyzed at the lab. Generally, the pre-analytical phase includes patient preparation, specimen transportation, specimen collection and storage. In the present study, we report the first comprehensive assessment of the frequency and types of pre-analytical errors at the Sulaimani diagnostic labs in Iraqi Kurdistan. Materials and Methods Over 2 months, 5500 venous blood samples were observed in 10 public diagnostic labs of Sulaimani City. The percentages of rejected samples and types of sample inappropriateness were evaluated. The percentage of each of the following pre-analytical errors were recorded: delay in sample transportation, clotted samples, expired reagents, hemolyzed samples, samples not on ice, incorrect sample identification, insufficient sample, tube broken in centrifuge, request procedure errors, sample mix-ups, communication conflicts, misinterpreted orders, lipemic samples, contaminated samples and missed physician’s request orders. The difference between the relative frequencies of errors observed in the hospitals considered was tested using a proportional Z test. In particular, the survey aimed to discover whether analytical errors were recorded and examine the types of platforms used in the selected diagnostic labs. Results The analysis showed a high prevalence of improper sample handling during the pre-analytical phase. In appropriate samples, the percentage error was as high as 39%. The major reasons for rejection were hemolyzed samples (9%), incorrect sample identification (8%) and clotted samples (6%). Most quality control schemes at Sulaimani hospitals focus only on the analytical phase, and none of the pre-analytical errors were recorded. Interestingly, none of the labs were internationally accredited; therefore, corrective actions are needed at these hospitals to ensure better health outcomes. Internal and External Quality Assessment Schemes (EQAS) for the pre-analytical phase at Sulaimani clinical laboratories should be implemented at public hospitals. Furthermore, lab personnel, particularly phlebotomists, need continuous training on the importance of sample quality to obtain accurate test results. PMID:28107395

Prevalence of Pre-Analytical Errors in Clinical Chemistry Diagnostic Labs in Sulaimani City of Iraqi Kurdistan.

PubMed

Najat, Dereen

2017-01-01

Laboratory testing is roughly divided into three phases: a pre-analytical phase, an analytical phase and a post-analytical phase. Most analytical errors have been attributed to the analytical phase. However, recent studies have shown that up to 70% of analytical errors reflect the pre-analytical phase. The pre-analytical phase comprises all processes from the time a laboratory request is made by a physician until the specimen is analyzed at the lab. Generally, the pre-analytical phase includes patient preparation, specimen transportation, specimen collection and storage. In the present study, we report the first comprehensive assessment of the frequency and types of pre-analytical errors at the Sulaimani diagnostic labs in Iraqi Kurdistan. Over 2 months, 5500 venous blood samples were observed in 10 public diagnostic labs of Sulaimani City. The percentages of rejected samples and types of sample inappropriateness were evaluated. The percentage of each of the following pre-analytical errors were recorded: delay in sample transportation, clotted samples, expired reagents, hemolyzed samples, samples not on ice, incorrect sample identification, insufficient sample, tube broken in centrifuge, request procedure errors, sample mix-ups, communication conflicts, misinterpreted orders, lipemic samples, contaminated samples and missed physician's request orders. The difference between the relative frequencies of errors observed in the hospitals considered was tested using a proportional Z test. In particular, the survey aimed to discover whether analytical errors were recorded and examine the types of platforms used in the selected diagnostic labs. The analysis showed a high prevalence of improper sample handling during the pre-analytical phase. In appropriate samples, the percentage error was as high as 39%. The major reasons for rejection were hemolyzed samples (9%), incorrect sample identification (8%) and clotted samples (6%). Most quality control schemes at Sulaimani hospitals focus only on the analytical phase, and none of the pre-analytical errors were recorded. Interestingly, none of the labs were internationally accredited; therefore, corrective actions are needed at these hospitals to ensure better health outcomes. Internal and External Quality Assessment Schemes (EQAS) for the pre-analytical phase at Sulaimani clinical laboratories should be implemented at public hospitals. Furthermore, lab personnel, particularly phlebotomists, need continuous training on the importance of sample quality to obtain accurate test results.

Practical solution for control of the pre-analytical phase in decentralized clinical laboratories for meeting the requirements of the medical laboratory accreditation standard DIN EN ISO 15189.

PubMed

Vacata, Vladimir; Jahns-Streubel, Gerlinde; Baldus, Mirjana; Wood, William Graham

2007-01-01

This report was written in response to the article by Wood published recently in this journal. It describes a practical solution to the problems of controlling the pre-analytical phase in the clinical diagnostic laboratory. As an indicator of quality in the pre-analytical phase of sample processing, a target analyte was chosen which is sensitive to delay in centrifugation and/or analysis. The results of analyses of the samples sent by satellite medical practitioners were compared with those from an on-site hospital laboratory with a controllable optimized pre-analytical phase. The aim of the comparison was: (a) to identify those medical practices whose mean/median sample values significantly deviate from those of the control situation in the hospital laboratory due to the possible problems in the pre-analytical phase; (b) to aid these laboratories in the process of rectifying these problems. A Microsoft Excel-based Pre-Analytical Survey tool (PAS tool) has been developed which addresses the above mentioned problems. It has been tested on serum potassium which is known to be sensitive to delay and/or irregularities in sample treatment. The PAS tool has been shown to be one possibility for improving the quality of the analyses by identifying the sources of problems within the pre-analytical phase, thus allowing them to be rectified. Additionally, the PAS tool has an educational value and can also be adopted for use in other decentralized laboratories.

75 FR 51830 - National Cancer Institute's Best Practices for Biospecimen Resources

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

... current federal guidance documents and recommendations from international biospecimen organizations. DATES... be directed to senior staff of the relevant NCI Extramural and Intramural Program offices...

Biospecimen Core Resource - TCGA

Cancer.gov

The Cancer Genome Atlas (TCGA) Biospecimen Core Resource centralized laboratory reviews and processes blood and tissue samples and their associated data using optimized standard operating procedures for the entire TCGA Research Network.

Advancing Translational Space Research Through Biospecimen Sharing: Amplified Impact of Studies Utilizing Analogue Space Platforms

NASA Technical Reports Server (NTRS)

Staten, B.; Moyer, E.; Vizir, V.; Gompf, H.; Hoban-Higgins, T.; Lewis, L.; Ronca, A.; Fuller, C. A.

2016-01-01

Biospecimen Sharing Programs (BSPs) have been organized by NASA Ames Research Center since the 1960s with the goal of maximizing utilization and scientific return from rare, complex and costly spaceflight experiments. BSPs involve acquiring otherwise unused biological specimens from primary space research experiments for distribution to secondary experiments. Here we describe a collaboration leveraging Ames expertise in biospecimen sharing to magnify the scientific impact of research informing astronaut health funded by the NASA Human Research Program (HRP) Human Health Countermeasures (HHC) Element. The concept expands biospecimen sharing to one-off ground-based studies utilizing analogue space platforms (e.g., Hindlimb Unloading (HLU), Artificial Gravity) for rodent experiments, thereby significantly broadening the range of research opportunities with translational relevance for protecting human health in space and on Earth.

Broad Consent for Research on Biospecimens: The Views of Actual Donors at Four U.S. Medical Centers.

PubMed

Warner, Teddy D; Weil, Carol J; Andry, Christopher; Degenholtz, Howard B; Parker, Lisa; Carithers, Latarsha J; Feige, Michelle; Wendler, David; Pentz, Rebecca D

2018-04-01

Commentators are concerned that broad consent may not provide biospecimen donors with sufficient information regarding possible future research uses of their tissue. We surveyed with interviews 302 cancer patients who had recently provided broad consent at four diverse academic medical centers. The majority of donors believed that the consent form provided them with sufficient information regarding future possible uses of their biospecimens. Donors expressed very positive views regarding tissue donation in general and endorsed the use of their biospecimens in future research across a wide range of contexts. Concerns regarding future uses were limited to for-profit research and research by investigators in other countries. These results support the use of broad consent to store and use biological samples in future research.

Regulating Research with Biospecimens under the Revised Common Rule.

PubMed

Lynch, Holly Fernandez; Meyer, Michelle N

2017-05-01

Since 2011, the research community had waited with bated breath as regulators contemplated for the first time bringing secondary research with nonidentifiable biospecimens under the Common Rule and dramatically tightening the criteria for waiving consent to biospecimen research. After considerable pushback from both researchers and patients and amid rumors of intractable disagreement among Common Rule agencies, the Final Rule published on the last day of President Obama's administration left out these troubling changes, and there was a collective sigh of relief. Relief is appropriate, but celebration premature: researchers have little reason to avail themselves of the new broad consent option offered in the Final Rule, and the question of whether biospecimens ought to be treated as inherently identifiable has merely been postponed. © 2017 The Hastings Center.

Negotiating Commercial Interests in Biospecimens.

PubMed

Roberts, Jessica L

2017-03-01

Proposed changes to the Common Rule would require publicly funded researchers to disclose whether a subject's biospecimens could be used for commercial profit and whether the subject will share in those proceeds. Disclosing commercial interests will inform research participants that their tissue may have commercial value, a possibility that those individuals might not have previously considered. The proposed changes may then provide people with an opportunity to negotiate commercial rights in their biospecimens despite the well-accepted legal precedent that individuals maintain no interests in their excised tissue.

NCI’s Cooperative Human Tissue Network

Cancer.gov

Quality biospecimens are a foundational resource for cancer research. One of NCI’s longest running biospecimen programs is the Cooperative Human Tissue Network, a resource mainly for basic discovery and early translational research.

A practical tool for modeling biospecimen user fees.

PubMed

Matzke, Lise; Dee, Simon; Bartlett, John; Damaraju, Sambasivarao; Graham, Kathryn; Johnston, Randal; Mes-Masson, Anne-Marie; Murphy, Leigh; Shepherd, Lois; Schacter, Brent; Watson, Peter H

2014-08-01

The question of how best to attribute the unit costs of the annotated biospecimen product that is provided to a research user is a common issue for many biobanks. Some of the factors influencing user fees are capital and operating costs, internal and external demand and market competition, and moral standards that dictate that fees must have an ethical basis. It is therefore important to establish a transparent and accurate costing tool that can be utilized by biobanks and aid them in establishing biospecimen user fees. To address this issue, we built a biospecimen user fee calculator tool, accessible online at www.biobanking.org . The tool was built to allow input of: i) annual operating and capital costs; ii) costs categorized by the major core biobanking operations; iii) specimen products requested by a biobank user; and iv) services provided by the biobank beyond core operations (e.g., histology, tissue micro-array); as well as v) several user defined variables to allow the calculator to be adapted to different biobank operational designs. To establish default values for variables within the calculator, we first surveyed the members of the Canadian Tumour Repository Network (CTRNet) management committee. We then enrolled four different participants from CTRNet biobanks to test the hypothesis that the calculator tool could change approaches to user fees. Participants were first asked to estimate user fee pricing for three hypothetical user scenarios based on their biobanking experience (estimated pricing) and then to calculate fees for the same scenarios using the calculator tool (calculated pricing). Results demonstrated significant variation in estimated pricing that was reduced by calculated pricing, and that higher user fees are consistently derived when using the calculator. We conclude that adoption of this online calculator for user fee determination is an important first step towards harmonization and realistic user fees.

Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer’s disease research

PubMed Central

Gupta, Veer; Henriksen, Kim; Edwards, Melissa; Jeromin, Andreas; Lista, Simone; Bazenet, Chantal; Soares, Holly; Lovestone, Simon; Hampel, Harald; Montine, Thomas; Blennow, Kaj; Foroud, Tatiana; Carrillo, Maria; Graff-Radford, Neill; Laske, Christoph; Breteler, Monique; Shaw, Leslie; Trojanowski, John Q.; Schupf, Nicole; Rissman, Robert A.; Fagan, Anne M.; Oberoi, Pankaj; Umek, Robert; Weiner, Michael W.; Grammas, Paula; Posner, Holly; Martins, Ralph

2015-01-01

The lack of readily available biomarkers is a significant hindrance towards progressing to effective therapeutic and preventative strategies for Alzheimer’s disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement provides (1) a synopsis of selected preanalytical methods utilized in many international AD cohort studies, (2) initial draft guidelines/SOPs for preanalytical methods, and (3) a list of required methodological information and protocols to be made available for publications in the field in order to foster cross-validation across cohorts and laboratories. PMID:25282381

Osteosarcoma enters a post genomic era with in silico opportunities: Generation of the High Dimensional Database for facilitating sarcoma biology research: A report from the Children's Oncology Group and the QuadW Foundation.

PubMed

Glover, Jason; Man, Tsz-Kwong; Barkauskas, Donald A; Hall, David; Tello, Tanya; Sullivan, Mary Beth; Gorlick, Richard; Janeway, Katherine; Grier, Holcombe; Lau, Ching; Toretsky, Jeffrey A; Borinstein, Scott C; Khanna, Chand; Fan, Timothy M

2017-01-01

The prospective banking of osteosarcoma tissue samples to promote research endeavors has been realized through the establishment of a nationally centralized biospecimen repository, the Children's Oncology Group (COG) biospecimen bank located at the Biopathology Center (BPC)/Nationwide Children's Hospital in Columbus, Ohio. Although the physical inventory of osteosarcoma biospecimens is substantive (>15,000 sample specimens), the nature of these resources remains exhaustible. Despite judicious allocation of these high-value biospecimens for conducting sarcoma-related research, a deeper understanding of osteosarcoma biology, in particular metastases, remains unrealized. In addition the identification and development of novel diagnostics and effective therapeutics remain elusive. The QuadW-COG Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) has developed the High Dimensional Data (HDD) platform to complement the existing physical inventory and to promote in silico hypothesis testing in sarcoma biology. The HDD is a relational biologic database derived from matched osteosarcoma biospecimens in which diverse experimental readouts have been generated and digitally deposited. As proof-of-concept, we demonstrate that the HDD platform can be utilized to address previously unrealized biologic questions though the systematic juxtaposition of diverse datasets derived from shared biospecimens. The continued population of the HDD platform with high-value, high-throughput and mineable datasets allows a shared and reusable resource for researchers, both experimentalists and bioinformatics investigators, to propose and answer questions in silico that advance our understanding of osteosarcoma biology.

Preanalytical quality in clinical chemistry laboratory.

PubMed

Ahmad, M Imteyaz; Ramesh, K L; Kumar, Ravi

2014-01-01

Haemolysis is usually caused by inadequate specimen collection or preanalytical handling and is suggested to be a suitable indicator of preanalytical quality. We investigated the prevalence of detectable haemolysis in all routine venous blood samples in OPDs and IPDs to identify differences in preanalytical quality. Haemolysis index (HI) values were obtained from a Vitros 5,1 in the routine clinical chemistry laboratory for samples collected in the outpatient department (OPD) collection centres, a hospital, and inpatient departments (IPD). Haemolysis was defined as a HI > or = 15 (detection limit). Samples from the OPD with the highest prevalence of haemolysis were 6.1 times (95% confidence interval (CI) 4.0 - 9.2) more often haemolysed compared to the center with the lowest prevalence. Of the samples collected in primary health care, 10.4% were haemolysed compared to 31.1% in the IPDs (p = 0.001). A notable difference in haemolysed samples was found between the IPDs section staffed by emergency medicine physicians and the section staffed by primary health care physicians (34.8% vs. 11.3%, p = 0.001). The significant variation in haemolysis indices among the investigated units is likely to reflect varying preanalytical conditions. The HI is a valuable tool for estimation and follow-up of preanalytical quality in the health care laboratory.

Clinical relevance of molecular diagnostics in gastrointestinal (GI) cancer: European Society of Digestive Oncology (ESDO) expert discussion and recommendations from the 17th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona.

PubMed

Baraniskin, Alexander; Van Laethem, Jean-Luc; Wyrwicz, Lucjan; Guller, Ulrich; Wasan, Harpreet S; Matysiak-Budnik, Tamara; Gruenberger, Thomas; Ducreux, Michel; Carneiro, Fatima; Van Cutsem, Eric; Seufferlein, Thomas; Schmiegel, Wolff

2017-11-01

In the epoch of precision medicine and personalised oncology, which aims to deliver the right treatment to the right patient, molecular genetic biomarkers are a topic of growing interest. The aim of this expert discussion and position paper is to review the current status of various molecular tests for gastrointestinal (GI) cancers and especially considering their significance for the clinical routine use. Opinion leaders and experts from diverse nationalities selected on scientific merit were asked to answer to a prepared set of questions about the current status of molecular diagnostics in different GI cancers. All answers were then discussed during a plenary session and reported here in providing a well-balanced reflection of both clinical expertise and updated evidence-based medicine. Preselected molecular genetic biomarkers that are described and disputed in the current medical literature in different GI cancers were debated, and recommendations for clinical routine practice were made whenever possible. Furthermore, the preanalytical variations were commented and proposals for quality controls of biospecimens were made. The current article summarises the recommendations of the expert committee regarding prognostic and predictive molecular genetic biomarkers in different entities of GI cancers. The briefly and comprehensively formulated guidelines should assist clinicians in the process of decision making in daily clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Proposed regulations for research with biospecimens: responses from stakeholders at CTSA consortium institutions.

PubMed

Botkin, Jeffrey R; Anderson, Rebecca; Murray, Tom; Beskow, Laura M; Maschke, Karen; Cuttler, Leona

2014-04-01

Secondary research with biospecimens acquired through clinical care and through research is often conducted without the informed consent of individuals from whom the specimens were acquired. While such uses are consistent with the current federal regulations, surveys of the general public suggest that many individuals would prefer more information and choice regarding research use of biospecimens. The federal government issued an Advance Notice of Proposed Rulemaking (ANPRM) in 2011 that proposed a number of potential changes in the regulations governing human subjects. These proposed regulations are particularly pertinent to institutions committed to research involving human subjects-including institutions in the NIH-funded Clinical and Translational Science Awards (CTSA) consortium. In this study, we reviewed public responses by CTSA-funded institutions and CTSA-affiliated organizations and groups regarding the proposed changes in the ANPRM with respect to research with biospecimens. Our results indicate that the majority of responses to the ANPRM from CTSA institutions were not supportive of the proposed changes. While many responses acknowledge a need to change current research practices regarding biospecimens, the proposed changes in the ANPRM received only limited support from this subgroup of academic research institutions. © 2014 Wiley Periodicals, Inc.

Proposed Regulations for Research with Biospecimens: Responses from Stakeholders at CTSA Consortium Institutions

PubMed Central

Botkin, Jeffrey R; Anderson, Rebecca; Murray, Tom; Beskow, Laura M.; Maschke, Karen; Cuttler, Leona

2014-01-01

Secondary research with biospecimens acquired through clinical care and through research is often conducted without the informed consent of individuals from whom the specimens were acquired. While such uses are consistent with the current federal regulations, surveys of the general public suggest that many individuals would prefer more information and choice regarding research use of biospecimens. The federal government issued an Advance Notice of Proposed Rulemaking (ANPRM) in 2011 that proposed a number of potential changes in the regulations governing human subjects. These proposed regulations are particularly pertinent to institutions committed to research involving human subjects – including institutions in the NIH-funded Clinical and Translational Science Awards (CTSA) consortium. In this study, we reviewed public responses by CTSA-funded institutions and CTS-affiliated organizations and groups regarding the proposed changes in the ANPRM with respect to research with biospecimens. Our results indicate that the majority of responses to the ANPRM from CTSA institutions were not supportive of the proposed changes. While many responses acknowledge a need to change current research practices regarding biospecimens, the proposed changes in the ANPRM received only limited support from this subgroup of academic research institutions. PMID:24459038

Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection

Cancer.gov

Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

Lessons from HeLa Cells: The Ethics and Policy of Biospecimens.

PubMed

Beskow, Laura M

2016-08-31

Human biospecimens have played a crucial role in scientific and medical advances. Although the ethical and policy issues associated with biospecimen research have long been the subject of scholarly debate, the story of Henrietta Lacks, her family, and the creation of HeLa cells captured the attention of a much broader audience. The story has been a catalyst for policy change, including major regulatory changes proposed in the United States surrounding informed consent. These proposals are premised in part on public opinion data, necessitating a closer look at what such data tell us. The development of biospecimen policy should be informed by many considerations-one of which is public input, robustly gathered, on acceptable approaches that optimize shared interests, including access for all to the benefits of research. There is a need for consent approaches that are guided by realistic aspirations and a balanced view of autonomy within an expanded ethical framework.

Lessons from HeLa Cells: The Ethics and Policy of Biospecimens

PubMed Central

Beskow, Laura M.

2016-01-01

Human biospecimens have played a crucial role in scientific and medical advances. Although the ethical and policy issues associated with biospecimen research have long been the subject of scholarly debate, the story of attention of a much broader audience. The story has been a catalyst for policy change, including major regulatory changes proposed in the United States surrounding informed consent. These proposals are premised in part on public opinion data, necessitating a closer look at what such data tell us. The development of biospecimen policy should be informed by many considerations—one of which is public input, robustly gathered, on acceptable approaches that optimize shared interests, including access for all to the benefits of research. There is a need for consent approaches that are guided by realistic aspirations and a balanced view of autonomy within an expanded ethical framework. PMID:26979405

The NASA Ames Life Sciences Data Archive: Biobanking for the Final Frontier

NASA Technical Reports Server (NTRS)

Rask, Jon; Chakravarty, Kaushik; French, Alison J.; Choi, Sungshin; Stewart, Helen J.

2017-01-01

The NASA Ames Institutional Scientific Collection involves the Ames Life Sciences Data Archive (ALSDA) and a biospecimen repository, which are responsible for archiving information and non-human biospecimens collected from spaceflight and matching ground control experiments. The ALSDA also manages a biospecimen sharing program, performs curation and long-term storage operations, and facilitates distribution of biospecimens for research purposes via a public website (https:lsda.jsc.nasa.gov). As part of our best practices, a tissue viability testing plan has been developed for the repository, which will assess the quality of samples subjected to long-term storage. We expect that the test results will confirm usability of the samples, enable broader science community interest, and verify operational efficiency of the archives. This work will also support NASA open science initiatives and guides development of NASA directives and policy for curation of biological collections.

Design and Implementation of a Prospective Adult Congenital Heart Disease Biobank.

PubMed

Opotowsky, Alexander R; Loukas, Brittani; Ellervik, Christina; Moko, Lilamarie E; Singh, Michael N; Landzberg, Elizabeth I; Rimm, Eric B; Landzberg, Michael J

2016-11-01

Adults with congenital heart disease (ACHD) comprise a growing, increasingly complex population. The Boston Adult Congenital Heart Disease Biobank is a program for the collection and storage of biospecimens to provide a sustainable resource for scientific biomarker investigation in ACHD. We describe a protocol to collect, process, and store biospecimens for ACHD or associated diagnoses developed based on existing literature and consultation with cardiovascular biomarker epidemiologists. The protocol involves collecting urine and ∼48.5 mL of blood. A subset of the blood and urine undergoes immediate clinically relevant testing. The remaining biospecimens are processed soon after collection and stored at -80°C as aliquots of ethylenediaminetetraacetic acid (EDTA) and lithium heparin plasma, serum, red cell and buffy coat pellet, and urine supernatant. Including tubes with diverse anticoagulant and clot accelerator contents will enable flexible downstream use. Demographic and clinical data are entered into a database; data on biospecimen collection, processing, and storage are managed by an enterprise laboratory information management system. Since implementation in 2012, we have enrolled more than 650 unique participants (aged 18-80 years, 53.3% women); the Biobank contains over 11,000 biospecimen aliquots. The most common primary CHD diagnoses are single ventricle status-post Fontan procedure (18.8%), repaired tetralogy of Fallot with pulmonary stenosis or atresia (17.6%), and left-sided obstructive lesions (17.5%). We describe the design and implementation of biospecimen collection, handling, and storage protocols with multiple levels of quality assurance. These protocols are feasible and reflect the size and goals of the Boston ACHD Biobank. © The Author(s) 2016.

Osteosarcoma enters a post genomic era with in silico opportunities: Generation of the High Dimensional Database for facilitating sarcoma biology research: A report from the Children's Oncology Group and the QuadW Foundation

PubMed Central

Glover, Jason; Man, Tsz-Kwong; Barkauskas, Donald A.; Hall, David; Tello, Tanya; Sullivan, Mary Beth; Gorlick, Richard; Janeway, Katherine; Grier, Holcombe; Lau, Ching; Toretsky, Jeffrey A.; Borinstein, Scott C.; Khanna, Chand

2017-01-01

The prospective banking of osteosarcoma tissue samples to promote research endeavors has been realized through the establishment of a nationally centralized biospecimen repository, the Children’s Oncology Group (COG) biospecimen bank located at the Biopathology Center (BPC)/Nationwide Children’s Hospital in Columbus, Ohio. Although the physical inventory of osteosarcoma biospecimens is substantive (>15,000 sample specimens), the nature of these resources remains exhaustible. Despite judicious allocation of these high-value biospecimens for conducting sarcoma-related research, a deeper understanding of osteosarcoma biology, in particular metastases, remains unrealized. In addition the identification and development of novel diagnostics and effective therapeutics remain elusive. The QuadW-COG Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) has developed the High Dimensional Data (HDD) platform to complement the existing physical inventory and to promote in silico hypothesis testing in sarcoma biology. The HDD is a relational biologic database derived from matched osteosarcoma biospecimens in which diverse experimental readouts have been generated and digitally deposited. As proof-of-concept, we demonstrate that the HDD platform can be utilized to address previously unrealized biologic questions though the systematic juxtaposition of diverse datasets derived from shared biospecimens. The continued population of the HDD platform with high-value, high-throughput and mineable datasets allows a shared and reusable resource for researchers, both experimentalists and bioinformatics investigators, to propose and answer questions in silico that advance our understanding of osteosarcoma biology. PMID:28732082

Intensive educational efforts combined with external quality assessment improve the preanalytical phase in general practitioner offices and nursing homes.

PubMed

Sølvik, Una Ørvim; Bjelkarøy, Wenche Iren; Berg, Kari van den; Saga, Anne Lise; Hager, Helle Borgstrøm; Sandberg, Sverre

2017-10-26

Errors in the preanalytical phase in clinical laboratories affect patient safety. The aim of this study was to evaluate the effect of intensive educational efforts together with external quality assessment (EQA) of the preanalytical phase from 2013 to 2015 to improve patient identification in primary health care in Norway. In addition, routines for venous and capillary blood sampling were investigated. A preanalytical EQA was circulated in 2013 by the Norwegian Quality Improvement of Laboratory Examinations (Noklus) to general practitioner offices and nursing homes (n=2000) to obtain information about important issues to focus on before launching an intensive educational program with courses, posters and visits in 2013-2015. Preanalytical EQA surveys were further circulated in 2014 and 2015. The response rate varied between 42% and 55%. The percentages of participants asking for the patients' name and the Norwegian identification number increased from about 8% in 2013 to about 35% in 2015. The increase was similar for those participating in only one EQA survey and for those who participated in EQA surveys both in 2013 and 2015. Guidelines for venous and capillary blood sampling were not always followed. Educational efforts more than the preanalytical EQA influenced the actions and resulted in an increase in the percentages of participants that followed the guidelines for patient identification. Some aspects of blood sampling routines need improvement.

Standardization and optimization of fluorescence in situ hybridization (FISH) for HER-2 assessment in breast cancer: A single center experience.

PubMed

Bogdanovska-Todorovska, Magdalena; Petrushevska, Gordana; Janevska, Vesna; Spasevska, Liljana; Kostadinova-Kunovska, Slavica

2018-05-20

Accurate assessment of human epidermal growth factor receptor 2 (HER-2) is crucial in selecting patients for targeted therapy. Commonly used methods for HER-2 testing are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Here we presented the implementation, optimization and standardization of two FISH protocols using breast cancer samples and assessed the impact of pre-analytical and analytical factors on HER-2 testing. Formalin fixed paraffin embedded (FFPE) tissue samples from 70 breast cancer patients were tested for HER-2 using PathVysion™ HER-2 DNA Probe Kit and two different paraffin pretreatment kits, Vysis/Abbott Paraffin Pretreatment Reagent Kit (40 samples) and DAKO Histology FISH Accessory Kit (30 samples). The concordance between FISH and IHC results was determined. Pre-analytical and analytical factors (i.e., fixation, baking, digestion, and post-hybridization washing) affected the efficiency and quality of hybridization. The overall hybridization success in our study was 98.6% (69/70); the failure rate was 1.4%. The DAKO pretreatment kit was more time-efficient and resulted in more uniform signals that were easier to interpret, compared to the Vysis/Abbott kit. The overall concordance between IHC and FISH was 84.06%, kappa coefficient 0.5976 (p < 0.0001). The greatest discordance (82%) between IHC and FISH was observed in IHC 2+ group. A standardized FISH protocol for HER-2 assessment, with high hybridization efficiency, is necessary due to variability in tissue processing and individual tissue characteristics. Differences in the pre-analytical and analytical steps can affect the hybridization quality and efficiency. The use of DAKO pretreatment kit is time-saving and cost-effective.

Measuring myokines with cardiovascular functions: pre-analytical variables affecting the analytical output.

PubMed

Lombardi, Giovanni; Sansoni, Veronica; Banfi, Giuseppe

2017-08-01

In the last few years, a growing number of molecules have been associated to an endocrine function of the skeletal muscle. Circulating myokine levels, in turn, have been associated with several pathophysiological conditions including the cardiovascular ones. However, data from different studies are often not completely comparable or even discordant. This would be due, at least in part, to the whole set of situations related to the preparation of the patient prior to blood sampling, blood sampling procedure, processing and/or store. This entire process constitutes the pre-analytical phase. The importance of the pre-analytical phase is often not considered. However, in routine diagnostics, the 70% of the errors are in this phase. Moreover, errors during the pre-analytical phase are carried over in the analytical phase and affects the final output. In research, for example, when samples are collected over a long time and by different laboratories, a standardized procedure for sample collecting and the correct procedure for sample storage are acknowledged. In this review, we discuss the pre-analytical variables potentially affecting the measurement of myokines with cardiovascular functions.

A role for research ethics committees in exchanges of human biospecimens through material transfer agreements.

PubMed

Chalmers, Donald; Nicol, Dianne; Nicolás, Pilar; Zeps, Nikolajs

2014-09-01

International transfers of human biological material (biospecimens) and data are increasing, and commentators are starting to raise concerns about how donor wishes are protected in such circumstances. These exchanges are generally made under contractual material transfer agreements (MTAs). This paper asks what role, if any, should research ethics committees (RECs) play in ensuring legal and ethical conduct in such exchanges. It is recommended that RECs should play a more active role in the future development of best practice MTAs involving exchange of biospecimens and data and in monitoring compliance.

The Biobank Economic Modeling Tool (BEMT): Online Financial Planning to Facilitate Biobank Sustainability

PubMed Central

Odeh, Hana; Miranda, Lisa; Rao, Abhi; Vaught, Jim; Greenman, Howard; McLean, Jeffrey; Reed, Daniel; Memon, Sarfraz; Fombonne, Benjamin; Guan, Ping

2015-01-01

Background: Biospecimens are essential resources for advancing basic and translational research. However, there are little data available regarding the costs associated with operating a biobank, and few resources to enable their long-term sustainability. To support the research community in this effort, the National Institutes of Health, National Cancer Institute's Biorepositories and Biospecimen Research Branch has developed the Biobank Economic Modeling Tool (BEMT). The tool is accessible at http://biospecimens.cancer.gov/resources/bemt.asp. Methods: To obtain market-based cost information and to inform the development of the tool, a survey was designed and sent to 423 biobank managers and directors across the world. The survey contained questions regarding infrastructure investments, salary costs, funding options, types of biospecimen resources and services offered, as well as biospecimen pricing and service-related costs. Results: A total of 106 responses were received. The data were anonymized, aggregated, and used to create a comprehensive database of cost and pricing information that was integrated into the web-based tool, the BEMT. The BEMT was built to allow the user to input cost and pricing data through a seven-step process to build a cost profile for their biobank, define direct and indirect costs, determine cost recovery fees, perform financial forecasting, and query the anonymized survey data from comparable biobanks. Conclusion: A survey was conducted to obtain a greater understanding of the costs involved in operating a biobank. The anonymized survey data was then used to develop the BEMT, a cost modeling tool for biobanks. Users of the tool will be able to create a cost profile for their biobanks' specimens, products and services, establish pricing, and allocate costs for biospecimens based on percent cost recovered, and perform project-specific cost analyses and financial forecasting. PMID:26697911

The Biobank Economic Modeling Tool (BEMT): Online Financial Planning to Facilitate Biobank Sustainability.

PubMed

Odeh, Hana; Miranda, Lisa; Rao, Abhi; Vaught, Jim; Greenman, Howard; McLean, Jeffrey; Reed, Daniel; Memon, Sarfraz; Fombonne, Benjamin; Guan, Ping; Moore, Helen M

2015-12-01

Biospecimens are essential resources for advancing basic and translational research. However, there are little data available regarding the costs associated with operating a biobank, and few resources to enable their long-term sustainability. To support the research community in this effort, the National Institutes of Health, National Cancer Institute's Biorepositories and Biospecimen Research Branch has developed the Biobank Economic Modeling Tool (BEMT). The tool is accessible at http://biospecimens.cancer.gov/resources/bemt.asp. To obtain market-based cost information and to inform the development of the tool, a survey was designed and sent to 423 biobank managers and directors across the world. The survey contained questions regarding infrastructure investments, salary costs, funding options, types of biospecimen resources and services offered, as well as biospecimen pricing and service-related costs. A total of 106 responses were received. The data were anonymized, aggregated, and used to create a comprehensive database of cost and pricing information that was integrated into the web-based tool, the BEMT. The BEMT was built to allow the user to input cost and pricing data through a seven-step process to build a cost profile for their biobank, define direct and indirect costs, determine cost recovery fees, perform financial forecasting, and query the anonymized survey data from comparable biobanks. A survey was conducted to obtain a greater understanding of the costs involved in operating a biobank. The anonymized survey data was then used to develop the BEMT, a cost modeling tool for biobanks. Users of the tool will be able to create a cost profile for their biobanks' specimens, products and services, establish pricing, and allocate costs for biospecimens based on percent cost recovered, and perform project-specific cost analyses and financial forecasting.

[Current modalities and concepts on access and use of biospecimen samples and associated data for research from human biobanks].

PubMed

Siddiqui, Roman; Semler, Sebastian Claudius

2016-03-01

It is accepted worldwide that biospecimen and data sharing (BDS) play an essential role for the future of medical research to improve diagnostics and prognostics, e.g. by validated biomarkers. BDS is also pivotal to the development of new therapeutic treatments and for the improvement of population health. Human biobanks can generate an added value to this need by providing biospecimens and/or associated data to researchers. An inspection of several examples of epidemiological as well as clinical/disease-oriented biobanks in Germany shows that best practice procedures (BPP) that are internationally agreed on are being installed for biospecimen and/or data access. In general, fair access is aimed at requiring a written application by the requesting scientist, which is then peer-reviewed for scientific and ethical validity by the Biobank. Applied BPP take into account (i) patient education/agreement according to the informed consent model, (ii) privacy protection, (iii) intellectual property rights, the (iv) notification obligation of health-related findings (including incidental findings), the (v) use of material (MTA) and data transfer agreements (DTA) for mutual legal security, the avoidance of conflicts of interests, as well as for cost recovery/fee for service as a basis for sustainability of the biobank. BPP are rooted in the self-regulation efforts of life sciences and are supported by parent ethics committees in Germany. Central biobank registries displaying aggregated information on biospecimens stored and the research foci constitute an important tool to make biobanks that are scattered across the country visible to each other, and, can thus promote access to hitherto unknown biospecimen and data resources.

MS-based monitoring of proteolytic decay of synthetic reporter peptides for quality control of plasma and serum specimens.

PubMed

Findeisen, Peter; Thumfart, Jörg Oliver; Costina, Victor; Hofheinz, Ralf; Neumaier, Michael

2013-09-01

To determine the preanalytical quality of serum and plasma by monitoring the time-dependent ex vivo decay of a synthetic reporter peptide (RP) with liquid chromatography/mass spectrometry (LC/MS). Serum and plasma specimens were spiked with the RP and proteolytic fragments were monitored with LC/MS at different preanalytical time points ranging from 2 to 24 hours after blood withdrawal. The concentration of fragments changed in a time-dependent manner, and respective peptide profiles were used to classify specimens according to their preanalytical time span. Classification accuracy was high, with values always above 0.89 for areas under receiver operating characteristic curves. This "proteomics degradation clock" can be used to estimate the preanalytical quality of serum and plasma and might have impact on quality control procedures of biobanking repositories.

Chemistry and haematology sample rejection and clinical impact in a tertiary laboratory in Cape Town.

PubMed

Jacobsz, Lourens A; Zemlin, Annalise E; Roos, Mark J; Erasmus, Rajiv T

2011-10-14

Recent publications report that up to 70% of total laboratory errors occur in the pre-analytical phase. Identification of specific problems highlights pre-analytic processes susceptible to errors. The rejection of unsuitable samples can lead to delayed turnaround time and affect patient care. A retrospective audit was conducted investigating the rejection rate of routine blood specimens received at chemistry and haematology laboratories over a 2-week period. The reasons for rejection and potential clinical impact of these rejections were investigated. Thirty patient files were randomly selected and examined to assess the impact of these rejections on clinical care. A total of 32,910 specimens were received during the study period, of which 481 were rejected, giving a rejection rate of 1.46%. The main reasons for rejection were inappropriate clotting (30%) and inadequate sample volume (22%). Only 51.7% of rejected samples were repeated and the average time for a repeat sample to reach the laboratory was about 5 days (121 h). Of the repeated samples, 5.1% had results within critical values. Examination of patient folders showed that in 40% of cases the rejection of samples had an impact on patient care. The evaluation of pre-analytical processes in the laboratory, with regard to sample rejection, allowed one to identify problem areas where improvement is necessary. Rejected samples due to factors out of the laboratory's control had a definite impact on patient care and can thus affect customer satisfaction. Clinicians should be aware of these factors to prevent such rejections.

Sources of Pre-Analytical Variations in Yield of DNA Extracted from Blood Samples: Analysis of 50,000 DNA Samples in EPIC

PubMed Central

Caboux, Elodie; Lallemand, Christophe; Ferro, Gilles; Hémon, Bertrand; Mendy, Maimuna; Biessy, Carine; Sims, Matt; Wareham, Nick; Britten, Abigail; Boland, Anne; Hutchinson, Amy; Siddiq, Afshan; Vineis, Paolo; Riboli, Elio; Romieu, Isabelle; Rinaldi, Sabina; Gunter, Marc J.; Peeters, Petra H. M.; van der Schouw, Yvonne T.; Travis, Ruth; Bueno-de-Mesquita, H. Bas; Canzian, Federico; Sánchez, Maria-José; Skeie, Guri; Olsen, Karina Standahl; Lund, Eiliv; Bilbao, Roberto; Sala, Núria; Barricarte, Aurelio; Palli, Domenico; Navarro, Carmen; Panico, Salvatore; Redondo, Maria Luisa; Polidoro, Silvia; Dossus, Laure; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Lagiou, Pagona; Boeing, Heiner; Fisher, Eva; Tumino, Rosario; Agnoli, Claudia; Hainaut, Pierre

2012-01-01

The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies. PMID:22808065

THE VALUE OF HOME-BASED COLLECTION OF BIOSPECIMENS IN REPRODUCTIVE EPIDEMIOLOGY

EPA Science Inventory

The Value of Home-Based Collection of Biospecimens in Reproductive Epidemiology
John C. Rockett1, Germaine M. Buck2, Courtney D. Johnson2 and Sally D. Perreault1
1Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Rese...

Establishment of a cervical cancer bio-bank for the Chinese population: from project-based sample collection to routine management.

PubMed

Yang, Ru; Li, Xiong; Zhou, Hang; Jia, Yao; Zhou, Jin; Huang, Kecheng; Tang, Fangxu; Hu, Ting; Shen, Jian; Chen, Zhilan; Wang, Shaoshuai; Sun, Haiying; Guo, Lili; Wang, Lin; Wang, Hui; Ma, Ding; Li, Shuang

2015-08-01

There is an increasing need for the establishment of a cervical cancer bio-bank that will facilitate both clinical and basic research. The cervical cancer bio-bank was first established in January 1999 and included two stages. First, a GWAS-based sample collection was conducted with special emphasis on the diagnosis and the retrieval of the corresponding bio-specimens, especially blood samples. Second, clinical data and their corresponding bio-specimens were routinely collected and handled. Notably, these bio-specimens also included samples from Wufeng Tujia Autonomous County, which has the highest incidence of cervical cancer in China. The specimens were collected from patients with cervical cancer and those with cervical intraepithelial neoplasia, while the control samples were collected from normal individuals. With special emphasis on clinical data and blood samples for the GWAS analysis, the collection of other bio-specimens was slow, and the pairing of specimens and clinical data was poor during the first stage. However, in the second stage, the pairing of the clinical data and its corresponding bio-specimens improved. At present, the samples procured and preserved in the bio-bank cover most regions of China and different ethnic groups for both the normal controls and cervical cancer patients of different pathological categories. This bio-bank of cervical cancer specimens from the Chinese population will greatly promote the studies of cervical cancer in China.

Quantitative assessment of prevalence of pre-analytical variables and their effect on coagulation assay. Can intervention improve patient safety?

PubMed

Bhushan, Ravi; Sen, Arijit

2017-04-01

Very few Indian studies exist on evaluation of pre-analytical variables affecting "Prothrombin Time" the commonest coagulation assay performed. The study was performed in an Indian tertiary care setting with an aim to assess quantitatively the prevalence of pre-analytical variables and their effects on the results (patient safety), for Prothrombin time test. The study also evaluated their effects on the result and whether intervention, did correct the results. The firstly evaluated the prevalence for various pre-analytical variables detected in samples sent for Prothrombin Time testing. These samples with the detected variables wherever possible were tested and result noted. The samples from the same patients were repeated and retested ensuring that no pre-analytical variable is present. The results were again noted to check for difference the intervention produced. The study evaluated 9989 samples received for PT/INR over a period of 18 months. The prevalence of different pre-analytical variables was found to be 862 (8.63%). The proportion of various pre-analytical variables detected were haemolysed samples 515 (5.16%), over filled vacutainers 62 (0.62%), under filled vacutainers 39 (0.39%), low values 205 (2.05%), clotted samples 11 (0.11%), wrong labeling 4 (0.04%), wrong vacutainer use 2 (0.02%), chylous samples 7 (0.07%) and samples with more than one variable 17 (0.17%). The comparison of percentage of samples showing errors were noted for the first variables since they could be tested with and without the variable in place. The reduction in error percentage was 91.5%, 69.2%, 81.5% and 95.4% post intervention for haemolysed, overfilled, under filled and samples collected with excess pressure at phlebotomy respectively. Correcting the variables did reduce the error percentage to a great extent in these four variables and hence the variables are found to affect "Prothrombin Time" testing and can hamper patient safety.

[Pre-analytical quality in fluid samples cytopathology: Results of a survey from the French Society of Clinical Cytology].

PubMed

Courtade-Saïdi, Monique; Fleury Feith, Jocelyne

2015-10-01

The pre-analytical step includes sample collection, preparation, transportation and storage in the pathology unit where the diagnosis is performed. The pathologist ensures that pre-analytical conditions are in line with expectations. The lack of standardization for handling cytological samples makes this pre-analytical step difficult to harmonize. Moreover, this step depends on the nature of the sample: fresh liquid or fixed material, air-dried smears, liquid-based cytology. The aim of the study was to review the different practices in French structures of pathology on the pre-analytical phase concerning cytological fluids such as broncho-alveolar lavage (BALF), serous fluids and urine. A survey was conducted on the basis of the pre-analytical chapter of the ISO 15189 and sent to 191 French pathological structures (105 public and 86 private). Fifty-six laboratories replied to the survey. Ninety-five per cent have a computerized management system and 70% a manual on sample handling. The general instructions requested for the patients and sample identification were highly correctly filled with a short time routing and additional tests prescription. By contrast, information are variable concerning the clinical information requested and the type of tubes for collecting fluids and the volumes required as well as the actions taken in case of non-conformity. For the specific items concerning BALF, serous fluids and urine, this survey has shown a great heterogeneity according to sample collection, fixation and of clinical information. This survey demonstrates that the pre-analytical quality for BALF, serous fluids and urine is not optimal and that some corrections of the practices are recommended with a standardization of numerous steps in order to increase the reproducibility of additional tests such as immunocytochemistry, cytogenetic and molecular biology. Some recommendations have been written. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The knowledge and understanding of preanalytical phase among biomedicine students at the University of Zagreb.

PubMed

Dukic, Lora; Jokic, Anja; Kules, Josipa; Pasalic, Daria

2016-01-01

The educational program for health care personnel is important for reducing preanalytical errors and improving quality of laboratory test results. The aim of our study was to assess the level of knowledge on preanalytical phase in population of biomedicine students through a cross-sectional survey. A survey was sent to students on penultimate and final year of Faculty of Pharmacy and Biochemistry--study of medical biochemistry (FPB), Faculty of Veterinary Medicine (FVM) and School of Medicine (SM), University of Zagreb, Croatia, using the web tool SurveyMonkey. Survey was composed of demographics and 14 statements regarding the preanalytical phase of laboratory testing. Comparison of frequencies and proportions of correct answers was done with Fisher's exact test and test of comparison of proportions, respectively. Study included 135 participants, median age 24 (23-40) years. Students from FPB had higher proportion of correct answers (86%) compared to students from other biomedical faculties 62%, P < 0.001. Students from FPB were more conscious of the importance of specimen mixing (P = 0.027), prevalence of preanalytical errors (P = 0.001), impact of hemolysis (P = 0.032) and lipemia interferences (P = 0.010), proper choice of anticoagulants (P = 0.001), transport conditions for ammonia sample (P < 0.001) and order of draw during blood specimen collection (P < 0.001), in comparison with students from SM and FVM. Students from FPB are more conscious of the importance of preanalytical phase of testing in comparison with their colleagues from other biomedical faculties. No difference in knowledge between penultimate and final year of the same faculty was found.

Evaluation of Preanalytical Quality Indicators by Six Sigma and Pareto`s Principle.

PubMed

Kulkarni, Sweta; Ramesh, R; Srinivasan, A R; Silvia, C R Wilma Delphine

2018-01-01

Preanalytical steps are the major sources of error in clinical laboratory. The analytical errors can be corrected by quality control procedures but there is a need for stringent quality checks in preanalytical area as these processes are done outside the laboratory. Sigma value depicts the performance of laboratory and its quality measures. Hence in the present study six sigma and Pareto principle was applied to preanalytical quality indicators to evaluate the clinical biochemistry laboratory performance. This observational study was carried out for a period of 1 year from November 2015-2016. A total of 1,44,208 samples and 54,265 test requisition forms were screened for preanalytical errors like missing patient information, sample collection details in forms and hemolysed, lipemic, inappropriate, insufficient samples and total number of errors were calculated and converted into defects per million and sigma scale. Pareto`s chart was drawn using total number of errors and cumulative percentage. In 75% test requisition forms diagnosis was not mentioned and sigma value of 0.9 was obtained and for other errors like sample receiving time, stat and type of sample sigma values were 2.9, 2.6, and 2.8 respectively. For insufficient sample and improper ratio of blood to anticoagulant sigma value was 4.3. Pareto`s chart depicts out of 80% of errors in requisition forms, 20% is contributed by missing information like diagnosis. The development of quality indicators, application of six sigma and Pareto`s principle are quality measures by which not only preanalytical, the total testing process can be improved.

Novel bone metabolism-associated hormones: the importance of the pre-analytical phase for understanding their physiological roles.

PubMed

Lombardi, Giovanni; Barbaro, Mosè; Locatelli, Massimo; Banfi, Giuseppe

2017-06-01

The endocrine function of bone is now a recognized feature of this tissue. Bone-derived hormones that modulate whole-body homeostasis, are being discovered as for the effects on bone of novel and classic hormones produced by other tissues become known. Often, however, the data regarding these last generation bone-derived or bone-targeting hormones do not give about a clear picture of their physiological roles or concentration ranges. A certain degree of uncertainty could stem from differences in the pre-analytical management of biological samples. The pre-analytical phase comprises a series of decisions and actions (i.e., choice of sample matrix, methods of collection, transportation, treatment and storage) preceding analysis. Errors arising in this phase will inevitably be carried over to the analytical phase where they can reduce the measurement accuracy, ultimately, leading discrepant results. While the pre-analytical phase is all important, in routine laboratory medicine, it is often not given due consideration in research and clinical trials. This is particularly true for novel molecules, such as the hormones regulating the endocrine function of bone. In this review we discuss the importance of the pre-analytical variables affecting the measurement of last generation bone-associated hormones and describe their, often debated and rarely clear physiological roles.

75 FR 66110 - Guidelines for Use of Stored Specimens and Access to Ancillary Data and Proposed Cost Schedule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-27

... repository of datasets from completed studies, biospecimens, and ancillary data. The Division intends to make... Sharing Policy. The Division has established an internal committee, the Biospecimen Repository Access and Data Sharing Committee (BRADSC), to oversee the repository access and data sharing program. The purpose...

Preanalytical Confounding Factors in the Analysis of Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: The Issue of Diurnal Variation

PubMed Central

Cicognola, Claudia; Chiasserini, Davide; Parnetti, Lucilla

2015-01-01

Given the growing use of cerebrospinal fluid (CSF) beta-amyloid (Aβ) and tau as biomarkers for early diagnosis of Alzheimer’s disease (AD), it is essential that the diagnostic procedures are standardized and the results comparable across different laboratories. Preanalytical factors are reported to be the cause of at least 50% of the total variability. Among them, diurnal variability is a key issue and may have an impact on the comparability of the values obtained. The available studies on this issue are not conclusive so far. Fluctuations of CSF biomarkers in young healthy volunteers have been previously reported, while subsequent studies have not confirmed those observations in older subjects, the ones most likely to receive this test. The observed differences in circadian rhythms need to be further assessed not only in classical CSF biomarkers but also in novel forthcoming biomarkers. In this review, the existing data on the issue of diurnal variations of CSF classical biomarkers for AD will be analyzed, also evaluating the available data on new possible biomarkers. PMID:26175714

Deciphering Sources of Variability in Clinical Pathology.

PubMed

Tripathi, Niraj K; Everds, Nancy E; Schultze, A Eric; Irizarry, Armando R; Hall, Robert L; Provencher, Anne; Aulbach, Adam

2017-01-01

The objectives of this session were to explore causes of variability in clinical pathology data due to preanalytical and analytical variables as well as study design and other procedures that occur in toxicity testing studies. The presenters highlighted challenges associated with such variability in differentiating test article-related effects from the effects of experimental procedures and its impact on overall data interpretation. These presentations focused on preanalytical and analytical variables and study design-related factors and their influence on clinical pathology data, and the importance of various factors that influence data interpretation including statistical analysis and reference intervals. Overall, these presentations touched upon potential effect of many variables on clinical pathology parameters, including animal physiology, sample collection process, specimen handling and analysis, study design, and some discussion points on how to manage those variables to ensure accurate interpretation of clinical pathology data in toxicity studies. This article is a brief synopsis of presentations given in a session entitled "Deciphering Sources of Variability in Clinical Pathology-It's Not Just about the Numbers" that occurred at the 35th Annual Symposium of the Society of Toxicologic Pathology in San Diego, California.

The NASA Ames Research Center Institutional Scientific Collection: History, Best Practices and Scientific Opportunities

NASA Technical Reports Server (NTRS)

Rask, Jon C.; Chakravarty, Kaushik; French, Alison; Choi, Sungshin; Stewart, Helen

2017-01-01

The NASA Ames Life Sciences Institutional Scientific Collection (ISC), which is composed of the Ames Life Sciences Data Archive (ALSDA) and the Biospecimen Storage Facility (BSF), is managed by the Space Biosciences Division and has been operational since 1993. The ALSDA is responsible for archiving information and animal biospecimens collected from life science spaceflight experiments and matching ground control experiments. Both fixed and frozen spaceflight and ground tissues are stored in the BSF within the ISC. The ALSDA also manages a Biospecimen Sharing Program, performs curation and long-term storage operations, and makes biospecimens available to the scientific community for research purposes via the Life Science Data Archive public website (https:lsda.jsc.nasa.gov). As part of our best practices, a viability testing plan has been developed for the ISC, which will assess the quality of archived samples. We expect that results from the viability testing will catalyze sample use, enable broader science community interest, and improve operational efficiency of the ISC. The current viability test plan focuses on generating disposition recommendations and is based on using ribonucleic acid (RNA) integrity number (RIN) scores as a criteria for measurement of biospecimen viablity for downstream functional analysis. The plan includes (1) sorting and identification of candidate samples, (2) conducting a statiscally-based power analysis to generate representaive cohorts from the population of stored biospecimens, (3) completion of RIN analysis on select samples, and (4) development of disposition recommendations based on the RIN scores. Results of this work will also support NASA open science initiatives and guides development of the NASA Scientific Collections Directive (a policy on best practices for curation of biological collections). Our RIN-based methodology for characterizing the quality of tissues stored in the ISC since the 1980s also creates unique scientific opportunities for temporal assessment across historical missions. Support from the NASA Space Biology Program and the NASA Human Research Program is gratefully acknowledged.

The knowledge and understanding of preanalytical phase among biomedicine students at the University of Zagreb

PubMed Central

Dukic, Lora; Jokic, Anja; Kules, Josipa; Pasalic, Daria

2016-01-01

Introduction The educational program for health care personnel is important for reducing preanalytical errors and improving quality of laboratory test results. The aim of our study was to assess the level of knowledge on preanalytical phase in population of biomedicine students through a cross-sectional survey. Materials and methods A survey was sent to students on penultimate and final year of Faculty of Pharmacy and Biochemistry – study of medical biochemistry (FPB), Faculty of Veterinary Medicine (FVM) and School of Medicine (SM), University of Zagreb, Croatia, using the web tool SurveyMonkey. Survey was composed of demographics and 14 statements regarding the preanalytical phase of laboratory testing. Comparison of frequencies and proportions of correct answers was done with Fisher’s exact test and test of comparison of proportions, respectively. Results Study included 135 participants, median age 24 (23-40) years. Students from FPB had higher proportion of correct answers (86%) compared to students from other biomedical faculties 62%, P < 0.001. Students from FPB were more conscious of the importance of specimen mixing (P = 0.027), prevalence of preanalytical errors (P = 0.001), impact of hemolysis (P = 0.032) and lipemia interferences (P = 0.010), proper choice of anticoagulants (P = 0.001), transport conditions for ammonia sample (P < 0.001) and order of draw during blood specimen collection (P < 0.001), in comparison with students from SM and FVM. Conclusions Students from FPB are more conscious of the importance of preanalytical phase of testing in comparison with their colleagues from other biomedical faculties. No difference in knowledge between penultimate and final year of the same faculty was found. PMID:26981023

Health professionals' opinions on supporting a cancer biobank: identification of barriers to combat biobanking pitfalls.

PubMed

Caixeiro, Nicole J; Byun, Hei Lan; Descallar, Joseph; Levesque, Janelle V; de Souza, Paul; Soon Lee, Cheok

2016-05-01

Although rarely acknowledged, a successful biobank is highly dependent on the support of the health professionals who assist the biobank in all aspects of its activities. In many cases, the lack of health professional support can be a limiting factor in the biobanking process of collecting and processing high-quality biospecimens. The aim of this study was to determine the attitudes of health professionals towards cancer biobanking. Using a 5-point Likert scale questionnaire, important aspects of biobanking, including accrual, quality, knowledge, responsiveness, impact, access, trust, governance and accreditation, were investigated. In total, 95 of 124 health and medical practitioners who were approached participated in this study (77% response rate). Health professionals in general supported the aims of biobanking with 56% of participants showing willingness to create a biobank and recruit donors (accrual), 85% understanding the importance in the storage and distribution of biospecimens (quality), 88% having an appreciation for the role of a biobank in furthering cancer research (knowledge), 70% showing awareness of the use of biospecimens in future research initiatives (responsiveness) and 73% demonstrating support for a biobank with proper control, authority and credibility measures in place (governance and accreditation). Overall, provided that proper information about the activities of the biobank and researcher access was transparent, health professionals were very willing to support cancer biobanking. These findings may assist in developing strategies for the establishment and maintenance of biobanks and aid the implementation of more effective policies and procedures to embed biobanking into routine hospital practices.

Pre-analytic and analytic sources of variations in thiopurine methyltransferase activity measurement in patients prescribed thiopurine-based drugs: A systematic review.

PubMed

Loit, Evelin; Tricco, Andrea C; Tsouros, Sophia; Sears, Margaret; Ansari, Mohammed T; Booth, Ronald A

2011-07-01

Low thiopurine S-methyltransferase (TPMT) enzyme activity is associated with increased thiopurine drug toxicity, particularly myelotoxicity. Pre-analytic and analytic variables for TPMT genotype and phenotype (enzyme activity) testing were reviewed. A systematic literature review was performed, and diagnostic laboratories were surveyed. Thirty-five studies reported relevant data for pre-analytic variables (patient age, gender, race, hematocrit, co-morbidity, co-administered drugs and specimen stability) and thirty-three for analytic variables (accuracy, reproducibility). TPMT is stable in blood when stored for up to 7 days at room temperature, and 3 months at -30°C. Pre-analytic patient variables do not affect TPMT activity. Fifteen drugs studied to date exerted no clinically significant effects in vivo. Enzymatic assay is the preferred technique. Radiochemical and HPLC techniques had intra- and inter-assay coefficients of variation (CVs) below 10%. TPMT is a stable enzyme, and its assay is not affected by age, gender, race or co-morbidity. Copyright © 2011. Published by Elsevier Inc.

21 CFR 866.4070 - RNA Preanalytical Systems.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false RNA Preanalytical Systems. 866.4070 Section 866.4070 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents § 866...

21 CFR 866.4070 - RNA Preanalytical Systems.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false RNA Preanalytical Systems. 866.4070 Section 866.4070 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents § 866...

21 CFR 866.4070 - RNA Preanalytical Systems.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false RNA Preanalytical Systems. 866.4070 Section 866.4070 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents § 866...

21 CFR 866.4070 - RNA Preanalytical Systems.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false RNA Preanalytical Systems. 866.4070 Section 866.4070 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents § 866...

21 CFR 866.4070 - RNA Preanalytical Systems.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false RNA Preanalytical Systems. 866.4070 Section 866.4070 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents § 866...

Review of Pre-Analytical Errors in Oral Glucose Tolerance Testing in a Tertiary Care Hospital.

PubMed

Nanda, Rachita; Patel, Suprava; Sahoo, Sibashish; Mohapatra, Eli

2018-03-13

The pre-pre-analytical and pre-analytical phases form a major chunk of the errors in a laboratory. The process has taken into consideration a very common procedure which is the oral glucose tolerance test to identify the pre-pre-analytical errors. Quality indicators provide evidence of quality, support accountability and help in the decision making of laboratory personnel. The aim of this research is to evaluate pre-analytical performance of the oral glucose tolerance test procedure. An observational study that was conducted overa period of three months, in the phlebotomy and accessioning unit of our laboratory using questionnaire that examined the pre-pre-analytical errors through a scoring system. The pre-analytical phase was analyzed for each sample collected as per seven quality indicators. About 25% of the population gave wrong answer with regard to the question that tested the knowledge of patient preparation. The appropriateness of test result QI-1 had the most error. Although QI-5 for sample collection had a low error rate, it is a very important indicator as any wrongly collected sample can alter the test result. Evaluating the pre-analytical and pre-pre-analytical phase is essential and must be conducted routinely on a yearly basis to identify errors and take corrective action and to facilitate their gradual introduction into routine practice.

Inpatient preanalytic process improvements.

PubMed

Wagar, Elizabeth A; Phipps, Ron; Del Guidice, Robert; Middleton, Lavinia P; Bingham, John; Prejean, Cheryl; Johnson-Hamilton, Martha; Philip, Pheba; Le, Ngoc Han; Muses, Waheed

2013-12-01

Phlebotomy services are a common target for preanalytic improvements. Many new, quality engineering tools have recently been applied in clinical laboratories. However, data on relatively few projects have been published. This example describes a complete application of current, quality engineering tools to improve preanalytic phlebotomy services. To decrease the response time in the preanalytic inpatient laboratory by 25%, to reduce the number of incident reports related to preanalytic phlebotomy, and to make systematic process changes that satisfied the stakeholders. The Department of Laboratory Medicine, General Services Section, at the University of Texas MD Anderson Cancer Center (Houston) is responsible for inpatient phlebotomy in a 24-hour operation, which serves 689 inpatient beds. The study director was project director of the Division of Pathology and Laboratory Medicine's Quality Improvement Section and was assisted by 2 quality technologists and an industrial engineer from MD Anderson Office of Performance Improvement. After implementing each solution, using well-recognized, quality tools and metrics, the response time for blood collection decreased by 23%, which was close to meeting the original responsiveness goal of 25%. The response time between collection and arrival in the laboratory decreased by 8%. Applicable laboratory-related incident reports were reduced by 43%. Comprehensive application of quality tools, such as statistical control charts, Pareto diagrams, value-stream maps, process failure modes and effects analyses, fishbone diagrams, solution prioritization matrices, and customer satisfaction surveys can significantly improve preset goals for inpatient phlebotomy.

Feasibility of Linking Population-Based Cancer Registries and Cancer Center Biorepositories

PubMed Central

McCusker, Margaret E.; Allen, Mark; Fernandez-Ami, Allyn; Gandour-Edwards, Regina

2012-01-01

Purpose: Biospecimen-based research offers tremendous promise as a way to increase understanding of the molecular epidemiology of cancers. Population-based cancer registries can augment this research by providing more clinical detail and long-term follow-up information than is typically available from biospecimen annotations. In order to demonstrate the feasibility of this concept, we performed a pilot linkage between the California Cancer Registry (CCR) and the University of California, Davis Cancer Center Biorepository (UCD CCB) databases to determine if we could identify patients with records in both databases. Methods: We performed a probabilistic data linkage between 2180 UCD CCB biospecimen records collected during the years 2005–2009 and all CCR records for cancers diagnosed from 1988–2009 based on standard data linkage procedures. Results: The 1040 UCD records with a unique medical record number, tissue site, and pathology date were linked to 3.3 million CCR records. Of these, 844 (81.2%) were identified in both databases. Overall, record matches were highest (100%) for cancers of the cervix and testis/other male genital system organs. For the most common cancers, matches were highest for cancers of the lung and respiratory system (93%), breast (91.7%), and colon and rectum (89.5%), and lower for prostate (72.9%). Conclusions: This pilot linkage demonstrated that information on existing biospecimens from a cancer center biorepository can be linked successfully to cancer registry data. Linkages between existing biorepositories and cancer registries can foster productive collaborations and provide a foundation for virtual biorepository networks to support population-based biospecimen research. PMID:24845042

Development and Validation of the Biobanking Attitudes and Knowledge Survey (BANKS)

PubMed Central

Wells, Kristen J.; Arevalo, Mariana; Meade, Cathy D.; Gwede, Clement K.; Quinn, Gwendolyn P.; Luque, John S.; Miguel, Gloria San; Watson, Dale; Phillips, Rebecca; Reyes, Carmen; Romo, Margarita; West, Jim; Jacobsen, Paul B.

2014-01-01

Background No validated multi-scale instruments exist that measure community members’ views on biobanking and biospecimen donation. This study describes the development and psychometric properties of the English-language BANKS (Biobanking Attitudes aNd Knowledge Survey). Methods The BANKS was created by item generation through review of scientific literature, focus groups with community members, and input from a community advisory board. Items were refined through cognitive interviews. Content validity was assessed through an expert panel review. Psychometric properties of the BANKS were assessed in a sample of 85 community members. Results The final BANKS includes 3 scales: Attitudes, Knowledge, and Self-Efficacy; as well as 3 single items, which evaluated receptivity and intention to donate a biospecimen for research. Cronbach's alpha coefficients for two scales that use Likert response format indicated high internal consistency (Attitudes: α=.88; Self-Efficacy: α=.95). Content validity indices were moderate, ranging from 0.69 to 0.89. Intention to donate blood and intention to donate urine were positively correlated with attitudes, knowledge, self-efficacy, and receptivity to learning more about biobanking (p's range from .029 to <.001). Conclusions The final BANKS shows evidence of satisfactory reliability and validity, is easy to administer, and is a promising tool to inform biospecimen research. Additional studies should be conducted with larger samples considering biospecimen donation to further assess the instrument's reliability and validity. Impact A valid and reliable instrument measuring community members’ views about biobanking may help researchers evaluate relevant communication interventions to enhance understanding, intention, and actual biospecimen donation. A Spanish-language BANKS is under development. PMID:24609846

Prostate Cancer Biorepository Network

DTIC Science & Technology

2016-10-01

Cancer Biorepository Network (PCBN). The aim of the PCBN is to provide prostate researchers with high- quality , well-annotated biospecimens obtained...patients and stores them to maintain high quality biospecimens. Additionally, clinical data including pathology and outcome data are annotated with the...that can provide to the wider research community. The major goal of the PCBN is to develop a biorepository with high- quality , well-annotated

A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens

PubMed Central

Becich, Michael J.; Bollag, Roni J.; Chavan, Girish; Corrigan, Julia; Dhir, Rajiv; Feldman, Michael D.; Gaudioso, Carmelo; Legowski, Elizabeth; Maihle, Nita J.; Mitchell, Kevin; Murphy, Monica; Sakthivel, Mayur; Tseytlin, Eugene; Weaver, JoEllen

2015-01-01

Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the TIES Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that is de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network. PMID:26670560

ASVCP quality assurance guidelines: control of preanalytical, analytical, and postanalytical factors for urinalysis, cytology, and clinical chemistry in veterinary laboratories.

PubMed

Gunn-Christie, Rebekah G; Flatland, Bente; Friedrichs, Kristen R; Szladovits, Balazs; Harr, Kendal E; Ruotsalo, Kristiina; Knoll, Joyce S; Wamsley, Heather L; Freeman, Kathy P

2012-03-01

In December 2009, the American Society for Veterinary Clinical Pathology (ASVCP) Quality Assurance and Laboratory Standards committee published the updated and peer-reviewed ASVCP Quality Assurance Guidelines on the Society's website. These guidelines are intended for use by veterinary diagnostic laboratories and veterinary research laboratories that are not covered by the US Food and Drug Administration Good Laboratory Practice standards (Code of Federal Regulations Title 21, Chapter 58). The guidelines have been divided into 3 reports: (1) general analytical factors for veterinary laboratory performance and comparisons; (2) hematology, hemostasis, and crossmatching; and (3) clinical chemistry, cytology, and urinalysis. This particular report is one of 3 reports and documents recommendations for control of preanalytical, analytical, and postanalytical factors related to urinalysis, cytology, and clinical chemistry in veterinary laboratories and is adapted from sections 1.1 and 2.2 (clinical chemistry), 1.3 and 2.5 (urinalysis), 1.4 and 2.6 (cytology), and 3 (postanalytical factors important in veterinary clinical pathology) of these guidelines. These guidelines are not intended to be all-inclusive; rather, they provide minimal guidelines for quality assurance and quality control for veterinary laboratory testing and a basis for laboratories to assess their current practices, determine areas for improvement, and guide continuing professional development and education efforts. © 2012 American Society for Veterinary Clinical Pathology.

Blood venous sample collection: Recommendations overview and a checklist to improve quality.

PubMed

Giavarina, Davide; Lippi, Giuseppe

2017-07-01

The extra-analytical phases of the total testing process have substantial impact on managed care, as well as an inherent high risk of vulnerability to errors which is often greater than that of the analytical phase. The collection of biological samples is a crucial preanalytical activity. Problems or errors occurring shortly before, or soon after, this preanalytical step may impair sample quality and characteristics, or else modify the final results of testing. The standardization of fasting requirements, rest, patient position and psychological state of the patient are therefore crucial for mitigating the impact of preanalytical variability. Moreover, the quality of materials used for collecting specimens, along with their compatibility, can guarantee sample quality and persistence of chemical and physical characteristics of the analytes over time, so safeguarding the reliability of testing. Appropriate techniques and sampling procedures are effective to prevent problems such as hemolysis, undue clotting in the blood tube, draw of insufficient sample volume and modification of analyte concentration. An accurate identification of both patient and blood samples is a key priority as for other healthcare activities. Good laboratory practice and appropriate training of operators, by specifically targeting collection of biological samples, blood in particular, may greatly improve this issue, thus lowering the risk of errors and their adverse clinical consequences. The implementation of a simple and rapid check-list, including verification of blood collection devices, patient preparation and sampling techniques, was found to be effective for enhancing sample quality and reducing some preanalytical errors associated with these procedures. The use of this tool, along with implementation of objective and standardized systems for detecting non-conformities related to unsuitable samples, can be helpful for standardizing preanalytical activities and improving the quality of laboratory diagnostics, ultimately helping to reaffirm a "preanalytical" culture founded on knowledge and real risk perception. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Hemolysis from a nurses' standpoint--survey from four Croatian hospitals.

PubMed

Dorotić, Adrijana; Antončić, Dragana; Biljak, Vanja Radišić; Nedić, Dara; Beletić, Andjelo

2015-01-01

Hemolysis can occur during sample collection, handling and transport. It is more frequent when the non-laboratory staff performs sampling. The aim of this study was to assess nurses' knowledge on the causes of hemolysis and consequential impact on the laboratory tests results. Additionally, the differences in knowledge, related to work experience, professional degree and previous education about hemolysis were explored. An anonymus survey, containing 11 questions on demographics, causes of hemolysis, its impact on biochemical parameters and nurses' attitude towards additional education in preanalytics, was conducted in four Croatian hospitals. The answers were compared by Chi-squared and Fischer exact test. In total, 562 survey results were collected. Majority of nurses declared familiarity with the term "hemolysis" (99.6%). There were 77% of correct answers regarding questions about the causes of hemolysis, but only 50% when it comes to questions about interference in biochemical tests. The percentage of correct answers about causes was significantly lower (P=0.029) among more experienced nurses, and higher (P=0.027) in those with higher professional degree, while influence of previous education was not significant. Also, higher percentage of correct answers about interferences was encountered in nurses with longer work experience (P=0.039). More than 70% of nurses declared that additional education about preanalytical factors would be beneficial. Croatian nurses are familiar with the definition of hemolysis, but a lack of knowledge about causes and influence on laboratory test results is evident. Nurses are eager to improve their knowledge in this field of preanalytical phase.

Thyroglobulin assay in fluids from lymph node fine needle-aspiration washout: influence of pre-analytical conditions.

PubMed

Casson, Florence Boux de; Moal, Valérie; Gauchez, Anne-Sophie; Moineau, Marie-Pierre; Sault, Corinne; Schlageter, Marie-Hélène; Massart, Catherine

2017-04-01

The aim of this study was to evaluate the pre-analytical factors contributing to uncertainty in thyroglobulin measurement in fluids from fine-needle aspiration (FNA) washout of cervical lymph nodes. We studied pre-analytical stability, in different conditions, of 41 samples prepared with concentrated solutions of thyroglobulin (FNA washout or certified standard) diluted in physiological saline solution or buffer containing 6% albumin. In this buffer, over time, no changes in thyroglobulin concentrations were observed in all storage conditions tested. In albumin free saline solution, thyroglobulin recovery rates depended on initial sample concentrations and on modalities of their conservation (in conventional storage tubes, recovery mean was 56% after 3 hours-storage at room temperature and 19% after 24 hours-storage for concentrations ranged from 2 to 183 μg/L; recovery was 95%, after 3 hours or 24 hours-storage at room temperature, for a concentration of 5,656 μg/L). We show here that these results are due to non-specific adsorption of thyroglobulin in storage tubes, which depends on sample protein concentrations. We also show that possible contamination of fluids from FNA washout by plasma proteins do not always adequately prevent this adsorption. In conclusion, non-specific adsorption in storage tubes strongly contributes to uncertainty in thyroglobulin measurement in physiological saline solution. It is therefore recommended, for FNA washout, to use a buffer containing proteins provided by the laboratory.

Pre-Analytical Considerations for Successful Next-Generation Sequencing (NGS): Challenges and Opportunities for Formalin-Fixed and Paraffin-Embedded Tumor Tissue (FFPE) Samples

PubMed Central

Arreaza, Gladys; Qiu, Ping; Pang, Ling; Albright, Andrew; Hong, Lewis Z.; Marton, Matthew J.; Levitan, Diane

2016-01-01

In cancer drug discovery, it is important to investigate the genetic determinants of response or resistance to cancer therapy as well as factors that contribute to adverse events in the course of clinical trials. Despite the emergence of new technologies and the ability to measure more diverse analytes (e.g., circulating tumor cell (CTC), circulating tumor DNA (ctDNA), etc.), tumor tissue is still the most common and reliable source for biomarker investigation. Because of its worldwide use and ability to preserve samples for many decades at ambient temperature, formalin-fixed, paraffin-embedded tumor tissue (FFPE) is likely to be the preferred choice for tissue preservation in clinical practice for the foreseeable future. Multiple analyses are routinely performed on the same FFPE samples (such as Immunohistochemistry (IHC), in situ hybridization, RNAseq, DNAseq, TILseq, Methyl-Seq, etc.). Thus, specimen prioritization and optimization of the isolation of analytes is critical to ensure successful completion of each assay. FFPE is notorious for producing suboptimal DNA quality and low DNA yield. However, commercial vendors tend to request higher DNA sample mass than what is actually required for downstream assays, which restricts the breadth of biomarker work that can be performed. We evaluated multiple genomics service laboratories to assess the current state of NGS pre-analytical processing of FFPE. Significant differences in pre-analytical capabilities were observed. Key aspects are highlighted and recommendations are made to improve the current practice in translational research. PMID:27657050

National Mesothelioma Virtual Bank: a standard based biospecimen and clinical data resource to enhance translational research.

PubMed

Amin, Waqas; Parwani, Anil V; Schmandt, Linda; Mohanty, Sambit K; Farhat, Ghada; Pople, Andrew K; Winters, Sharon B; Whelan, Nancy B; Schneider, Althea M; Milnes, John T; Valdivieso, Federico A; Feldman, Michael; Pass, Harvey I; Dhir, Rajiv; Melamed, Jonathan; Becich, Michael J

2008-08-13

Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. The National Mesothelioma Virtual Bank architecture is based on three major components: (a) common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards), (b) clinical and epidemiologic data annotation, and (c) data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid (caBIG, see http://cabig.nci.nih.gov). This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational research. Furthermore, it protects patient privacy by disclosing only de-identified datasets to assure that biospecimens can be made accessible to researchers.

The State of Cloud-Based Biospecimen and Biobank Data Management Tools.

PubMed

Paul, Shonali; Gade, Aditi; Mallipeddi, Sumani

2017-04-01

Biobanks are critical for collecting and managing high-quality biospecimens from donors with appropriate clinical annotation. The high-quality human biospecimens and associated data are required to better understand disease processes. Therefore, biobanks have become an important and essential resource for healthcare research and drug discovery. However, collecting and managing huge volumes of data (biospecimens and associated clinical data) necessitate that biobanks use appropriate data management solutions that can keep pace with the ever-changing requirements of research. To automate biobank data management, biobanks have been investing in traditional Laboratory Information Management Systems (LIMS). However, there are a myriad of challenges faced by biobanks in acquiring traditional LIMS. Traditional LIMS are cost-intensive and often lack the flexibility to accommodate changes in data sources and workflows. Cloud technology is emerging as an alternative that provides the opportunity to small and medium-sized biobanks to automate their operations in a cost-effective manner, even without IT personnel. Cloud-based solutions offer the advantage of heightened security, rapid scalability, dynamic allocation of services, and can facilitate collaboration between different research groups by using a shared environment on a "pay-as-you-go" basis. The benefits offered by cloud technology have resulted in the development of cloud-based data management solutions as an alternative to traditional on-premise software. After evaluating the advantages offered by cloud technology, several biobanks have started adopting cloud-based tools. Cloud-based tools provide biobanks with easy access to biospecimen data for real-time sharing with clinicians. Another major benefit realized by biobanks by implementing cloud-based applications is unlimited data storage on the cloud and automatic backups for protecting any data loss in the face of natural calamities.

Intact stable isotope labeled plasma proteins from the SILAC-labeled HepG2 secretome.

PubMed

Mangrum, John B; Martin, Erika J; Brophy, Donald F; Hawkridge, Adam M

2015-09-01

The plasma proteome remains an attractive biospecimen for MS-based biomarker discovery studies. The success of these efforts relies on the continued development of quantitative MS-based proteomics approaches. Herein we report the use of the SILAC-labeled HepG2 secretome as a source for stable isotope labeled plasma proteins for quantitative LC-MS/MS measurements. The HepG2 liver cancer cell line secretes the major plasma proteins including serum albumin, apolipoproteins, protease inhibitors, coagulation factors, and transporters that represent some of the most abundant proteins in plasma. The SILAC-labeled HepG2 secretome was collected, spiked into human plasma (1:1 total protein), and then processed for LC-MS/MS analysis. A total of 62 and 56 plasma proteins were quantified (heavy:light (H/L) peptide pairs) from undepleted and depleted (serum albumin and IgG), respectively, with log2 H/L = ± 6. Major plasma proteins quantified included albumin, apolipoproteins (e.g., APOA1, APOA2, APOA4, APOB, APOC3, APOE, APOH, and APOM), protease inhibitors (e.g., A2M and SERPINs), coagulation factors (e.g., Factor V, Factor X, fibrinogen), and transport proteins (e.g., TTR). The average log2 H/L values for shared plasma proteins in both undepleted and depleted plasma samples were 0.43 and 0.44, respectively. This work further expands the SILAC strategy into MS-based biomarker discovery of clinical biospecimens. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ethics of clear health communication: applying the CLEAN Look approach to communicate biobanking information for cancer research.

PubMed

Koskan, Alexis; Arevalo, Mariana; Gwede, Clement K; Quinn, Gwendolyn P; Noel-Thomas, Shalewa A; Luque, John S; Wells, Kristen J; Meade, Cathy D

2012-11-01

Cancer innovations, such as biobanking technologies, are continuously evolving to improve our understanding and knowledge about cancer prevention and treatment modalities. However, the public receives little communication about biobanking and is often unaware about this innovation until asked to donate biospecimens. It is the researchers' ethical duty to provide clear communications about biobanking and biospecimen research. Such information allows the public to understand biobanking processes and facilitates informed decision making about biospecimen donation. The aims of this paper are 1) to examine the importance of clear communication as an ethical imperative when conveying information about cancer innovations and 2) to illustrate the use of an organizing framework, the CLEAN ( C ulture, L iteracy, E ducation, A ssessment, and N etworking) Look approach for creating educational priming materials about the topic of biobanking.

Prostate Cancer Pathology Resource Network

DTIC Science & Technology

2013-07-01

The PCBN is organized with a Coordinating Center (JHU – led by Bruce Trock, Ph.D.), and Network Sites at NYU (led by Jonathan Melamed, M.D. and Peng...Resource Network Site must contribute biospecimens from a minimum of 50 patients per year, with the expectation that biospecimen contribution will...available to the Pathology Resource Network Site . o Each year both sites have contributed over 500 newly accrued specimens, with specimens obtained as

Transmissive liquid-crystal device for correcting primary coma aberration and astigmatism in biospecimen in two-photon excitation laser scanning microscopy

NASA Astrophysics Data System (ADS)

Tanabe, Ayano; Hibi, Terumasa; Ipponjima, Sari; Matsumoto, Kenji; Yokoyama, Masafumi; Kurihara, Makoto; Hashimoto, Nobuyuki; Nemoto, Tomomi

2016-12-01

All aberrations produced inside a biospecimen can degrade the quality of a three-dimensional image in two-photon excitation laser scanning microscopy. Previously, we developed a transmissive liquid-crystal device to correct spherical aberrations that improved the image quality of a fixed-mouse-brain slice treated with an optical clearing reagent. In this study, we developed a transmissive device that corrects primary coma aberration and astigmatism. The motivation for this study is that asymmetric aberration can be induced by the shape of a biospecimen and/or by a complicated refractive-index distribution in a sample; this can considerably degrade optical performance even near the sample surface. The device's performance was evaluated by observing fluorescence beads. The device was inserted between the objective lens and microscope revolver and succeeded in improving the spatial resolution and fluorescence signal of a bead image that was originally degraded by asymmetric aberration. Finally, we implemented the device for observing a fixed whole mouse brain with a sloping surface shape and complicated internal refractive-index distribution. The correction with the device improved the spatial resolution and increased the fluorescence signal by ˜2.4×. The device can provide a simple approach to acquiring higher-quality images of biospecimens.

Accelerating the Development and Validation of New Value-Based Diagnostics by Leveraging Biobanks.

PubMed

Schneider, Daniel; Riegman, Peter H J; Cronin, Maureen; Negrouk, Anastassia; Moch, Holger; Balling, Rudi; Penault-Llorca, Frederiques; Zatloukal, Kurt; Horgan, Denis

The challenges faced in developing value-based diagnostics has resulted in few of these tests reaching the clinic, leaving many treatment modalities without matching diagnostics to select patients for particular therapies. Many patients receive therapies from which they are unlikely to benefit, resulting in worse outcomes and wasted health care resources. The paucity of value-based diagnostics is a result of the scientific challenges in developing predictive markers, specifically: (1) complex biology, (2) a limited research infrastructure supporting diagnostic development, and (3) the lack of incentives for diagnostic developers to invest the necessary resources. Better access to biospecimens can address some of these challenges. Methodologies developed to evaluate biomarkers from biospecimens archived from patients enrolled in randomized clinical trials offer the greatest opportunity to develop and validate high-value molecular diagnostics. An alternative opportunity is to access high-quality biospecimens collected from large public and private longitudinal observational cohorts such as the UK Biobank, the US Million Veteran Program, the UK 100,000 Genomes Project, or the French E3N cohort. Value-based diagnostics can be developed to work in a range of samples including blood, serum, plasma, urine, and tumour tissue, and better access to these high-quality biospecimens with clinical data can facilitate biomarker research. © 2016 S. Karger AG, Basel.

Public perspectives on biospecimen procurement: what biorepositories should consider.

PubMed

L'Heureux, Jamie; Murray, Jeffrey C; Newbury, Elizabeth; Shinkunas, Laura; Simon, Christian M

2013-06-01

Human biospecimens are central to biobanking efforts, yet how members of the public think about biobank procurement strategies is not well understood. This study aimed to explore public perspectives toward the procurement of residual clinical material versus "direct" procurement strategies such as the drawing of blood. Members of the public residing in and beyond the biobank catchment area of the University of Iowa Hospitals and Clinics were randomly selected to participate in focus groups and a telephone survey. The majority of survey participants (75%, n=559) found both residual and direct procurement strategies equally workable. Small proportions preferred either residual (15%; n=117) or direct (5%; n=40) procurement. Focus group participants (n=48) could identify benefits to both procurement strategies, but raised concerns about possible donor inconvenience/discomfort and reduced biospecimen accrual in the case of direct procurement. Residual procurement raised concerns about lower-quality samples being procured without full donor awareness. Biobanks should consider that members of the public in their research programs may be willing to make specimen donations regardless of whether a residual or direct procurement strategy is employed. Limiting patient discomfort and inconvenience may make direct procurement strategies more acceptable to some members of the public. Ensuring donor awareness through effective informed consent may allay public concerns about the indirectness of donating clinical biospecimens.

Tissue Banking, Bioinformatics, and Electronic Medical Records: The Front-End Requirements for Personalized Medicine

PubMed Central

Suh, K. Stephen; Sarojini, Sreeja; Youssif, Maher; Nalley, Kip; Milinovikj, Natasha; Elloumi, Fathi; Russell, Steven; Pecora, Andrew; Schecter, Elyssa; Goy, Andre

2013-01-01

Personalized medicine promises patient-tailored treatments that enhance patient care and decrease overall treatment costs by focusing on genetics and “-omics” data obtained from patient biospecimens and records to guide therapy choices that generate good clinical outcomes. The approach relies on diagnostic and prognostic use of novel biomarkers discovered through combinations of tissue banking, bioinformatics, and electronic medical records (EMRs). The analytical power of bioinformatic platforms combined with patient clinical data from EMRs can reveal potential biomarkers and clinical phenotypes that allow researchers to develop experimental strategies using selected patient biospecimens stored in tissue banks. For cancer, high-quality biospecimens collected at diagnosis, first relapse, and various treatment stages provide crucial resources for study designs. To enlarge biospecimen collections, patient education regarding the value of specimen donation is vital. One approach for increasing consent is to offer publically available illustrations and game-like engagements demonstrating how wider sample availability facilitates development of novel therapies. The critical value of tissue bank samples, bioinformatics, and EMR in the early stages of the biomarker discovery process for personalized medicine is often overlooked. The data obtained also require cross-disciplinary collaborations to translate experimental results into clinical practice and diagnostic and prognostic use in personalized medicine. PMID:23818899

Reverse transcription-polymerase chain reaction molecular testing of cytology specimens: Pre-analytic and analytic factors.

PubMed

Bridge, Julia A

2017-01-01

The introduction of molecular testing into cytopathology laboratory practice has expanded the types of samples considered feasible for identifying genetic alterations that play an essential role in cancer diagnosis and treatment. Reverse transcription-polymerase chain reaction (RT-PCR), a sensitive and specific technical approach for amplifying a defined segment of RNA after it has been reverse-transcribed into its DNA complement, is commonly used in clinical practice for the identification of recurrent or tumor-specific fusion gene events. Real-time RT-PCR (quantitative RT-PCR), a technical variation, also permits the quantitation of products generated during each cycle of the polymerase chain reaction process. This review addresses qualitative and quantitative pre-analytic and analytic considerations of RT-PCR as they relate to various cytologic specimens. An understanding of these aspects of genetic testing is central to attaining optimal results in the face of the challenges that cytology specimens may present. Cancer Cytopathol 2017;125:11-19. © 2016 American Cancer Society. © 2016 American Cancer Society.

TRWG developmental pathway for biospecimen-based assessment modalities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Translational Research Working Group; Srivastava, Sudhir; Gray, Joe W.

The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of NCI's investment in translational research and envision its future. The TRWG conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of biospecimen-based assays that utilize biomarkers for the detection, diagnosis, prognosis, and assessment of response to cancer treatment. The biospecimen-based assessment modality (BM) pathway was conceived not as comprehensive description of the corresponding real-world processes, but rather as a tool designed to facilitate movement of a candidatemore » assay through the translational process to the point where it can be handed off for definitive clinical testing. This paper introduces the pathway in the context of prior work and discusses key challenges associated with the biomarker development process in light of the pathway.« less

ASVCP quality assurance guidelines: control of preanalytical and analytical factors for hematology for mammalian and nonmammalian species, hemostasis, and crossmatching in veterinary laboratories.

PubMed

Vap, Linda M; Harr, Kendal E; Arnold, Jill E; Freeman, Kathleen P; Getzy, Karen; Lester, Sally; Friedrichs, Kristen R

2012-03-01

In December 2009, the American Society for Veterinary Clinical Pathology (ASVCP) Quality Assurance and Laboratory Standards committee published the updated and peer-reviewed ASVCP Quality Assurance Guidelines on the Society's website. These guidelines are intended for use by veterinary diagnostic laboratories and veterinary research laboratories that are not covered by the US Food and Drug Administration Good Laboratory Practice standards (Code of Federal Regulations Title 21, Chapter 58). The guidelines have been divided into 3 reports: (1) general analytical factors for veterinary laboratory performance and comparisons; (2) hematology, hemostasis, and crossmatching; and (3) clinical chemistry, cytology, and urinalysis. This particular report is one of 3 reports and provides recommendations for control of preanalytical and analytical factors related to hematology for mammalian and nonmammalian species, hemostasis testing, and crossmatching and is adapted from sections 1.1 and 2.3 (mammalian hematology), 1.2 and 2.4 (nonmammalian hematology), 1.5 and 2.7 (hemostasis testing), and 1.6 and 2.8 (crossmatching) of the complete guidelines. These guidelines are not intended to be all-inclusive; rather, they provide minimal guidelines for quality assurance and quality control for veterinary laboratory testing and a basis for laboratories to assess their current practices, determine areas for improvement, and guide continuing professional development and education efforts. © 2012 American Society for Veterinary Clinical Pathology.

Hemolysis from a nurses’ standpoint – survey from four Croatian hospitals

PubMed Central

Dorotić, Adrijana; Antončić, Dragana; Biljak, Vanja Radišić; Nedić, Dara; Beletić, Andjelo

2015-01-01

Introduction Hemolysis can occur during sample collection, handling and transport. It is more frequent when the non-laboratory staff performs sampling. The aim of this study was to assess nurses’ knowledge on the causes of hemolysis and consequential impact on the laboratory tests results. Additionally, the differences in knowledge, related to work experience, professional degree and previous education about hemolysis were explored. Materials and methods An anonymus survey, containing 11 questions on demographics, causes of hemolysis, its impact on biochemical parameters and nurses’ attitude towards additional education in preanalytics, was conducted in four Croatian hospitals. The answers were compared by Chi-squared and Fischer exact test. Results In total, 562 survey results were collected. Majority of nurses declared familiarity with the term “hemolysis” (99.6%). There were 77% of correct answers regarding questions about the causes of hemolysis, but only 50% when it comes to questions about interference in biochemical tests. The percentage of correct answers about causes was significantly lower (P = 0.029) among more experienced nurses, and higher (P = 0.027) in those with higher professional degree, while influence of previous education was not significant. Also, higher percentage of correct answers about interferences was encountered in nurses with longer work experience (P = 0.039). More than 70% of nurses declared that additional education about preanalytical factors would be beneficial. Conclusion Croatian nurses are familiar with the definition of hemolysis, but a lack of knowledge about causes and influence on laboratory test results is evident. Nurses are eager to improve their knowledge in this field of preanalytical phase. PMID:26525069

Safeguarding donors' personal rights and biobank autonomy in biobank networks: the CRIP privacy regime.

PubMed

Schröder, Christina; Heidtke, Karsten R; Zacherl, Nikolaus; Zatloukal, Kurt; Taupitz, Jochen

2011-08-01

Governance, underlying general ICT (Information and Communication Technology) architecture, and workflow of the Central Research Infrastructure for molecular Pathology (CRIP) are discussed as a model enabling biobank networks to form operational "meta biobanks" whilst respecting the donors' privacy, biobank autonomy and confidentiality, and the researchers' needs for appropriate biospecimens and information, as well as confidentiality. Tailored to these needs, CRIP efficiently accelerates and facilitates research with human biospecimens and data.

Population Based Analysis of Hematologic Malignancy Referrals to a Comprehensive Cancer Center, Referrals for Blood and Marrow Transplantation, and Participation in Clinical Trials, Survey and Biospecimen Research by Race

PubMed Central

Clay, Alyssa; Peoples, Brittany; Zhang, Yali; Moysich, Kirsten; Ross, Levi; McCarthy, Philip; Hahn, Theresa

2017-01-01

Racial and ethnic disparities have been reported in clinical trial/research participation, utilization of autologous and allogeneic BMT and availability of allogeneic donors. We performed a population-based cohort study to investigate adult hematologic malignancy referrals to a U.S tertiary cancer center, utilization of BMT and participation in clinical trials, survey and biospecimen research, by race. U.S. Census Data and the New York State Public Access Cancer Epidemiology Database identified the racial distribution of the general population and new hematologic malignancy cases in the primary catchment area. From 2005–2011, 1,106 patients aged 18–75 years were referred for BMT consultation; while the rate of BMT among hematologic malignancy referrals did not differ by race, the reasons for not receiving a BMT did. Participation in biospecimen research did not vary by race, however African-Americans and other minorities were significantly less likely to participate in survey research than European-Americans. While rates of hematologic malignancy referrals and use of BMT for minorities appear low (<10%), they closely reflect the race distribution of all hematologic malignancy cases and the Western New York population. African-Americans are equally likely as other races to participate in biospecimen banking, but further study is needed to understand reasons for lower participation in survey research. PMID:25899454

Public Perspectives on Biospecimen Procurement: What Biorepositories Should Consider

PubMed Central

L'Heureux, Jamie; Murray, Jeffrey C.; Newbury, Elizabeth; Shinkunas, Laura

2013-01-01

Purpose Human biospecimens are central to biobanking efforts, yet how members of the public think about biobank procurement strategies is not well understood. This study aimed to explore public perspectives toward the procurement of residual clinical material versus “direct” procurement strategies such as the drawing of blood. Methods Members of the public residing in and beyond the biobank catchment area of the University of Iowa Hospitals and Clinics were randomly selected to participate in focus groups and a telephone survey. Results The majority of survey participants (75%, n=559) found both residual and direct procurement strategies equally workable. Small proportions preferred either residual (15%; n=117) or direct (5%; n=40) procurement. Focus group participants (n=48) could identify benefits to both procurement strategies, but raised concerns about possible donor inconvenience/discomfort and reduced biospecimen accrual in the case of direct procurement. Residual procurement raised concerns about lower-quality samples being procured without full donor awareness. Conclusion Biobanks should consider that members of the public in their research programs may be willing to make specimen donations regardless of whether a residual or direct procurement strategy is employed. Limiting patient discomfort and inconvenience may make direct procurement strategies more acceptable to some members of the public. Ensuring donor awareness through effective informed consent may allay public concerns about the indirectness of donating clinical biospecimens. PMID:24850089

[Pre-analytical stage for biomarker assessment in breast cancer: 2014 update of the GEFPICS' guidelines in France].

PubMed

MacGrogan, Gaëtan; Mathieu, Marie-Christine; Poulet, Bruno; Penault-Llorca, Frédérique; Vincent-Salomon, Anne; Roger, Pascal; Treilleux, Isabelle; Valent, Alexander; Antoine, Martine; Becette, Véronique; Bor, Catherine; Brabencova, Eva; Charafe-Jauffret, Emmanuelle; Chenard, Marie-Pierre; Dauplat, Marie-Mélanie; Delrée, Paul; Devouassoux, Mojgan; Fiche, Maryse; Fondrevelle, Marie-Eve; Fridman, Viviana; Garbar, Christian; Genin, Pascal; Ghnassia, Jean-Pierre; Haudebourg, Juliette; Laberge-Le Couteulx, Sophie; Loussouarn, Delphine; Maran-Gonzalez, Aurélie; Marcy, Myriam; Michenet, Patrick; Sagan, Christine; Trassard, Martine; Verriele, Véronique; Arnould, Laurent; Lacroix-Triki, Magali

2014-10-01

Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation and specimen handling protocols must be standardized, validated and carefully tracked. Cooperation and training of the personnel involved in the specimen workflow (e.g. radiologists, surgeons, nurses, technicians and pathologists) are of paramount importance. The GEFPICS' update of the recommendations herein details and comments the different steps of the pre-analytical process. Application of these guidelines and participation to quality insurance programs are mandatory to ensure the correct evaluation of oncotheranostic biomarkers. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Thawing as a critical pre-analytical step in the lipidomic profiling of plasma samples: New standardized protocol.

PubMed

Pizarro, Consuelo; Arenzana-Rámila, Irene; Pérez-del-Notario, Nuria; Pérez-Matute, Patricia; González-Sáiz, José María

2016-03-17

Lipid profiling is a promising tool for the discovery and subsequent identification of biomarkers associated with various diseases. However, data quality is quite dependent on the pre-analytical methods employed. To date, potential confounding factors that may affect lipid metabolite levels after the thawing of plasma for biomarker exploration studies have not been thoroughly evaluated. In this study, by means of experimental design methodology, we performed the first in-depth examination of the ways in which thawing conditions affect lipid metabolite levels. After the optimization stage, we concluded that temperature, sample volume and the thawing method were the determining factors that had to be exhaustively controlled in the thawing process to ensure the quality of biomarker discovery. Best thawing conditions were found to be: 4 °C, with 0.25 mL of human plasma and ultrasound (US) thawing. The new US proposed thawing method was quicker than the other methods we studied, allowed more features to be identified and increased the signal of the lipids. In view of its speed, efficiency and detectability, the US thawing method appears to be a simple, economical method for the thawing of plasma samples, which could easily be applied in clinical laboratories before lipid profiling studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Exploring phlebotomy technique as a pre-analytical factor in proteomic analyses by mass spectrometry.

PubMed

Penn, Andrew M; Lu, Linghong; Chambers, Andrew G; Balshaw, Robert F; Morrison, Jaclyn L; Votova, Kristine; Wood, Eileen; Smith, Derek S; Lesperance, Maria; del Zoppo, Gregory J; Borchers, Christoph H

2015-12-01

Multiple reaction monitoring mass spectrometry (MRM-MS) is an emerging technology for blood biomarker verification and validation; however, the results may be influenced by pre-analytical factors. This exploratory study was designed to determine if differences in phlebotomy techniques would significantly affect the abundance of plasma proteins in an upcoming biomarker development study. Blood was drawn from 10 healthy participants using four techniques: (1) a 20-gauge IV with vacutainer, (2) a 21-gauge direct vacutainer, (3) an 18-gauge butterfly with vacutainer, and (4) an 18-gauge butterfly with syringe draw. The abundances of a panel of 122 proteins (117 proteins, plus 5 matrix metalloproteinase (MMP) proteins) were targeted by LC/MRM-MS. In addition, complete blood count (CBC) data were also compared across the four techniques. Phlebotomy technique significantly affected 2 of the 11 CBC parameters (red blood cell count, p = 0.010; hemoglobin concentration, p = 0.035) and only 12 of the targeted 117 proteins (p < 0.05). Of the five MMP proteins, only MMP7 was detectable and its concentration was not significantly affected by different techniques. Overall, most proteins in this exploratory study were not significantly influenced by phlebotomy technique; however, a larger study with additional patients will be required for confirmation.

Exhaled breath condensate – from an analytical point of view

PubMed Central

Dodig, Slavica; Čepelak, Ivana

2013-01-01

Over the past three decades, the goal of many researchers is analysis of exhaled breath condensate (EBC) as noninvasively obtained sample. A total quality in laboratory diagnostic processes in EBC analysis was investigated: pre-analytical (formation, collection, storage of EBC), analytical (sensitivity of applied methods, standardization) and post-analytical (interpretation of results) phases. EBC analysis is still used as a research tool. Limitations referred to pre-analytical, analytical, and post-analytical phases of EBC analysis are numerous, e.g. low concentrations of EBC constituents, single-analyte methods lack in sensitivity, and multi-analyte has not been fully explored, and reference values are not established. When all, pre-analytical, analytical and post-analytical requirements are met, EBC biomarkers as well as biomarker patterns can be selected and EBC analysis can hopefully be used in clinical practice, in both, the diagnosis and in the longitudinal follow-up of patients, resulting in better outcome of disease. PMID:24266297

International Charter of principles for sharing bio-specimens and data.

PubMed

Mascalzoni, Deborah; Dove, Edward S; Rubinstein, Yaffa; Dawkins, Hugh J S; Kole, Anna; McCormack, Pauline; Woods, Simon; Riess, Olaf; Schaefer, Franz; Lochmüller, Hanns; Knoppers, Bartha M; Hansson, Mats

2015-06-01

There is a growing international agreement on the need to provide greater access to research data and bio-specimen collections to optimize their long-term value and exploit their potential for health discovery and validation. This is especially evident for rare disease research. Currently, the rising value of data and bio-specimen collections does not correspond with an equal increase in data/sample-sharing and data/sample access. Contradictory legal and ethical frameworks across national borders are obstacles to effective sharing: more specifically, the absence of an integrated model proves to be a major logistical obstruction. The Charter intends to amend the obstacle by providing both the ethical foundations on which data sharing should be based, as well as a general Material and Data Transfer Agreement (MTA/DTA). This Charter is the result of a careful negotiation of different stakeholders' interest and is built on earlier consensus documents and position statements, which provided the general international legal framework. Further to this, the Charter provides tools that may help accelerate sharing. The Charter has been formulated to serve as an enabling tool for effective and transparent data and bio-specimen sharing and the general MTA/DTA constitutes a mechanism to ensure uniformity of access across projects and countries, and may be regarded as a consistent basic agreement for addressing data and material sharing globally. The Charter is forward looking in terms of emerging issues from the perspective of a multi-stakeholder group, and where possible, provides strategies that may address these issues.

Population-Based Analysis of Hematologic Malignancy Referrals to a Comprehensive Cancer Center, Referrals for Blood and Marrow Transplantation, and Participation in Clinical Trial, Survey, and Biospecimen Research by Race.

PubMed

Clay, Alyssa; Peoples, Brittany; Zhang, Yali; Moysich, Kirsten; Ross, Levi; McCarthy, Philip; Hahn, Theresa

2015-08-01

Racial and ethnic disparities have been reported in clinical trial/research participation, utilization of autologous and allogeneic blood and marrow transplantation (BMT), and availability of allogeneic donors. We performed a population-based cohort study to investigate adult hematologic malignancy referrals to a US tertiary cancer center, utilization of BMT, and participation in clinical trial, survey, and biospecimen research by race. US Census Data and the New York State Public Access Cancer Epidemiology Database identified the racial distribution of the general population and new hematologic malignancy cases in the primary catchment area. From 2005 to 2011, 1106 patients aged 18 to 75 years were referred for BMT consultation; although the rate of BMT among hematologic malignancy referrals did not differ by race, the reasons for not receiving a BMT did. Participation in biospecimen research did not vary by race; however, African Americans and other minorities were significantly less likely to participate in survey research than European Americans. Although rates of hematologic malignancy referrals and use of BMT for minorities appear to be low (<10%), they closely reflect the race distribution of all hematologic malignancy cases and the western New York population. African Americans are equally likely as other races to participate in biospecimen banking, but further study is needed to understand reasons for lower participation in survey research. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Identification of Analytical Factors Affecting Complex Proteomics Profiles Acquired in a Factorial Design Study with Analysis of Variance: Simultaneous Component Analysis.

PubMed

Mitra, Vikram; Govorukhina, Natalia; Zwanenburg, Gooitzen; Hoefsloot, Huub; Westra, Inge; Smilde, Age; Reijmers, Theo; van der Zee, Ate G J; Suits, Frank; Bischoff, Rainer; Horvatovich, Péter

2016-04-19

Complex shotgun proteomics peptide profiles obtained in quantitative differential protein expression studies, such as in biomarker discovery, may be affected by multiple experimental factors. These preanalytical factors may affect the measured protein abundances which in turn influence the outcome of the associated statistical analysis and validation. It is therefore important to determine which factors influence the abundance of peptides in a complex proteomics experiment and to identify those peptides that are most influenced by these factors. In the current study we analyzed depleted human serum samples to evaluate experimental factors that may influence the resulting peptide profile such as the residence time in the autosampler at 4 °C, stopping or not stopping the trypsin digestion with acid, the type of blood collection tube, different hemolysis levels, differences in clotting times, the number of freeze-thaw cycles, and different trypsin/protein ratios. To this end we used a two-level fractional factorial design of resolution IV (2(IV)(7-3)). The design required analysis of 16 samples in which the main effects were not confounded by two-factor interactions. Data preprocessing using the Threshold Avoiding Proteomics Pipeline (Suits, F.; Hoekman, B.; Rosenling, T.; Bischoff, R.; Horvatovich, P. Anal. Chem. 2011, 83, 7786-7794, ref 1) produced a data-matrix containing quantitative information on 2,559 peaks. The intensity of the peaks was log-transformed, and peaks having intensities of a low t-test significance (p-value > 0.05) and a low absolute fold ratio (<2) between the two levels of each factor were removed. The remaining peaks were subjected to analysis of variance (ANOVA)-simultaneous component analysis (ASCA). Permutation tests were used to identify which of the preanalytical factors influenced the abundance of the measured peptides most significantly. The most important preanalytical factors affecting peptide intensity were (1) the hemolysis level, (2) stopping trypsin digestion with acid, and (3) the trypsin/protein ratio. This provides guidelines for the experimentalist to keep the ratio of trypsin/protein constant and to control the trypsin reaction by stopping it with acid at an accurately set pH. The hemolysis level cannot be controlled tightly as it depends on the status of a patient's blood (e.g., red blood cells are more fragile in patients undergoing chemotherapy) and the care with which blood was sampled (e.g., by avoiding shear stress). However, its level can be determined with a simple UV spectrophotometric measurement and samples with extreme levels or the peaks affected by hemolysis can be discarded from further analysis. The loadings of the ASCA model led to peptide peaks that were most affected by a given factor, for example, to hemoglobin-derived peptides in the case of the hemolysis level. Peak intensity differences for these peptides were assessed by means of extracted ion chromatograms confirming the results of the ASCA model.

Using Lean-Six Sigma to reduce hemolysis in the emergency care center in a collaborative quality improvement project with the hospital laboratory.

PubMed

Damato, Charlotte; Rickard, Dana

2015-03-01

As part of a strategic quality improvement plan, laboratory management at Sarasota Memorial Health Care System (SMHCS) focused its efforts on improving preanalytical work flow and blood collection processes-both negatively affected by hemolyzed specimens. When hemolysis is detected in a blood specimen, blood may need to be re-collected, resulting in bottlenecks and rework all along the value stream. From July through December 2009, hemolysis averaged 9.8% in the Emergency Care Center (ECC) and 3.4% housewide. The goal was set to reduce hemolysis to 2%. The project team identified hemolysis as one of seven factors contributing to non-value-added activities and bottlenecks in blood collection and preanalytical processes. Observations and interviews helped to identify error-prone practices and process variation. To verify the root causes of hemolysis, the findings were compared against best practices. The team developed a housewide protocol, standardized collection processes, created competency-based training, and enhanced ECC hiring practices. During December 2010-March 2011, following initial housewide interventions and ECC self-sustaining solutions, ECC hemolysis decreased by 91%-from 9.8% (423 hemolyzed/4,295 collected) to 0.88% (58 hemolyzed/6,560 collected). Housewide hemolysis decreased by 59%-from 3.4% (2,046 hemolyzed/60,307 collected) to 1.39% (619 hemolyzed/44,528 collected). Since the project, hemolysis has continued to trend downward; the mean percentage has consistently been < .05% for the ECC and < 1% housewide. Lean-Six Sigma tools helped to pinpoint hemolysis as a key inefficiency in blood collection and preanalytical work flow. Although focused on the ECC, the project team standardized blood collection practices and instituted quality devices to achieve hemolysis reductions housewide.

Trace element reference values in tissues from inhabitants of the European Community. III. The control of preanalytical factors in the biomonitoring of trace elements in biological fluids.

PubMed

Minoia, C; Pietra, R; Sabbioni, E; Ronchi, A; Gatti, A; Cavalleri, A; Manzo, L

1992-06-09

In the context of a programme concerning the determination of trace elements in body fluids and tissues to establish trace element reference values, research has been undertaken on the control of preanalytical factors in order to develop sufficiently accurate and precise guidelines to be applied in routine work by using techniques such as graphite furnace atomic absorption spectroscopy (GFAAS). Aspects investigated are related to the risk of contamination during blood collection and the use of anticoagulants; the risk of losses during storage and freeze-drying as well as the possible risk of contamination arising from trace elements in airborne particulates of the laboratory environment. For the analysis of Al, Ba, Cd, Co, Cr, Mn, Mo, Ni, Sb, W, V and Zn in blood, Teflon cannula is the method of choice. The anticoagulants do not introduce disturbing contaminations of Rb, Se, Zn, while contaminations were observed for Co, Cr, Mn. Radiotracers in 'metabolized form' (radiolabelled rat or rabbit tissues from animals administered with radioisotopes) show that samples stored for 1 month at -20 degrees C have no significant trace metal losses. Strict ambient air quality standard has to be respected (continuous monitoring) due to the possibility of element contaminations inside the laboratory. The use of matrix modifiers could represent a toxicological risk to the operators. Critical factors should be considered ('metal sheets') for each element in each matrix. For instance 27 factors for Cr in serum have been suggested.

National survey on the pre-analytical variability in a representative cohort of Italian laboratories.

PubMed

Lippi, Giuseppe; Montagnana, Martina; Giavarina, Davide

2006-01-01

Owing to remarkable advances in automation, laboratory technology and informatics, the pre-analytical phase has become the major source of variability in laboratory testing. The present survey investigated the development of several pre-analytical processes within a representative cohort of Italian clinical laboratories. A seven-point questionnaire was designed to investigate the following issues: 1a) the mean outpatient waiting time before check-in and 1b) the mean time from check-in to sample collection; 2) the mean time from sample collection to analysis; 3) the type of specimen collected for clinical chemistry testing; 4) the degree of pre-analytical automation; 5a) the number of samples shipped to other laboratories and 5b) the availability of standardised protocols for transportation; 6) the conditions for specimen storage; and 7) the availability and type of guidelines for management of unsuitable specimens. The questionnaire was administered to 150 laboratory specialists attending the SIMEL (Italian Society of Laboratory Medicine) National Meeting in June 2006. 107 questionnaires (71.3%) were returned. Data analysis revealed a high degree of variability among laboratories for the time required for check-in, outpatient sampling, sample transportation to the referral laboratory and analysis upon the arrival. Only 31% of laboratories have automated some pre-analytical steps. Of the 87% of laboratories that ship specimens to other facilities without sample preparation, 19% have no standardised protocol for transportation. For conventional clinical chemistry testing, 74% of the laboratories use serum evacuated tubes (59% with and 15% without serum separator), whereas the remaining 26% use lithium-heparin evacuated tubes (11% with and 15% without plasma separator). The storage period and conditions for rerun/retest vary widely. Only 63% of laboratories have a codified procedure for the management of unsuitable specimens, which are recognised by visual inspection (69%) or automatic detection (29%). Only 56% of the laboratories have standardised procedures for the management of unsuitable specimens, which vary widely on a local basis. The survey highlights broad heterogeneity in several pre-analytical processes among Italian laboratories. The lack of reliable guidelines encompassing evidence-based practice is a major problem for the standardisation of this crucial part of the testing process and represents a major challenge for laboratory medicine in the 2000s.

The Childhood Leukemia International Consortium

PubMed Central

Metayer, Catherine; Milne, Elizabeth; Clavel, Jacqueline; Infante-Rivard, Claire; Petridou, Eleni; Taylor, Malcolm; Schüz, Joachim; Spector, Logan G.; Dockerty, John D.; Magnani, Corrado; Pombo-de-Oliveira, Maria S.; Sinnett, Daniel; Murphy, Michael; Roman, Eve; Monge, Patricia; Ezzat, Sameera; Mueller, Beth A.; Scheurer, Michael E.; Armstrong, Bruce K.; Birch, Jill; Kaatsch, Peter; Koifman, Sergio; Lightfoot, Tracy; Bhatti, Parveen; Bondy, Melissa L.; Rudant, Jérémie; O’Neill, Kate; Miligi, Lucia; Dessypris, Nick; Kang, Alice Y.; Buffler, Patricia A.

2013-01-01

Background Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case–control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene–environment interactions. Objectives The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene–environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods By September 2012, CLIC included 22 studies (recruitment period: 1962–present) from 12 countries, totaling approximately 31 000 cases and 50 000 controls. Of these, 19 case–control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child–parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene–environment interactions and associations among specific leukemia subtypes in different ethnic groups. PMID:23403126

Extracting DNA from FFPE Tissue Biospecimens Using User-Friendly Automated Technology: Is There an Impact on Yield or Quality?

PubMed

Mathieson, William; Guljar, Nafia; Sanchez, Ignacio; Sroya, Manveer; Thomas, Gerry A

2018-05-03

DNA extracted from formalin-fixed, paraffin-embedded (FFPE) tissue blocks is amenable to analytical techniques, including sequencing. DNA extraction protocols are typically long and complex, often involving an overnight proteinase K digest. Automated platforms that shorten and simplify the process are therefore an attractive proposition for users wanting a faster turn-around or to process large numbers of biospecimens. It is, however, unclear whether automated extraction systems return poorer DNA yields or quality than manual extractions performed by experienced technicians. We extracted DNA from 42 FFPE clinical tissue biospecimens using the QiaCube (Qiagen) and ExScale (ExScale Biospecimen Solutions) automated platforms, comparing DNA yields and integrities with those from manual extractions. The QIAamp DNA FFPE Spin Column Kit was used for manual and QiaCube DNA extractions and the ExScale extractions were performed using two of the manufacturer's magnetic bead kits: one extracting DNA only and the other simultaneously extracting DNA and RNA. In all automated extraction methods, DNA yields and integrities (assayed using DNA Integrity Numbers from a 4200 TapeStation and the qPCR-based Illumina FFPE QC Assay) were poorer than in the manual method, with the QiaCube system performing better than the ExScale system. However, ExScale was fastest, offered the highest reproducibility when extracting DNA only, and required the least intervention or technician experience. Thus, the extraction methods have different strengths and weaknesses, would appeal to different users with different requirements, and therefore, we cannot recommend one method over another.

[Optimization of blood gas analysis in intensive care units : Reduction of preanalytical errors and improvement of workflow].

PubMed

Kieninger, M; Zech, N; Mulzer, Y; Bele, S; Seemann, M; Künzig, H; Schneiker, A; Gruber, M

2015-05-01

Point of care testing with blood gas analysis (BGA) is an important factor for intensive care medicine. Continuous efforts to optimize workflow, improve safety for the staff and avoid preanalytical mistakes are important and should reflect quality management standards. In a prospective observational study it was investigated whether the implementation of a new system for BGA using labeled syringes and automated processing of the specimens leads to improvements compared to the previously used procedure. In a 4-week test period the time until receiving the final results of the BGA with the standard method used in the clinical routine (control group) was compared to the results in a second 4-week test period using the new labeled syringes and automated processing of the specimens (intervention group). In addition, preanalytical mistakes with both systems were checked during routine daily use. Finally, it was investigated whether a delay of 10 min between taking and analyzing the blood samples alters the results of the BGA. Preanalytical errors were frequently observed in the control group where non-deaerated samples were recorded in 87.3 % but in the intervention group almost all samples (98.9 %) were correctly deaerated. Insufficient homogenization due to omission of manual pivoting was seen in 83.2 % in the control group and in 89.9 % in the intervention group; however, in the intervention group the samples were homogenized automatically during the further analytical process. Although a survey among the staff revealed a high acceptance of the new system and a subjective improvement of workflow, a measurable gain in time after conversion to the new procedure could not be seen. The mean time needed for a complete analysis process until receiving the final results was 244 s in the intervention group and 201 s in the control group. A 10-min delay between taking and analyzing the blood samples led to a significant and clinically relevant elevation of the values for partial pressure of oxygen (pO2) in both groups compared to the results when analyzing the samples immediately (118.4 vs. 148.6 mmHg in the control group and 115.3 vs. 123.7 mmHg in the intervention group). When using standard syringes the partial pressure of carbon dioxide (pCO2) was significantly lower (40.5 vs. 38.3 mmHg) whereas no alterations were seen when using the labeled syringes. The implementation of a new BGA system with labeled syringes and automated processing of the specimens was possible without any difficulties under daily clinical routine conditions in this 10-bed intensive care unit (ICU). A gain of time could not be measured but a reduction in preanalytical errors using the labeled syringes with automated processing was found. Delayed analysis of blood samples can lead to significant changes in pO2 and pCO2 depending on the type of syringe used.

Biobanking of blood and bone marrow: emerging challenges for custodians of public resources.

PubMed

Aparicio, Lorena; Lipworth, Wendy; Then, Shih-Ning; Stewart, Cameron; Coghlan, Patrick; Kerridge, Ian; Fleming, Jennifer

2013-12-01

The Australian Bone Marrow Donor Registry (ABMDR) is a publicly funded company that is part of an international network that facilitates unrelated bone marrow transplantation. This role means that the ABMDR has access to a large biospecimen repository therefore making it a highly valuable research resource. Recognising the potential value of these biospecimens for research purposes, the ABMDR is in the process of determining whether, and how, to share its biospecimens with other biobanks. While this would undoubtedly be of value to the scientific community, and ultimately to the wider community, it would also inevitably transform the role of an institution whose primary role is therapeutic, and would compromise the degree of control that a custodian has over donated material. This article describe the challenges confronting the ABMDR, and organisations like it, in balancing their duties to donors, patients, researchers and the general public. These problems have led inevitably to the use of "property" rights language in the discussion of these issues but notions of gift, ownership, trusteeship and transfer might also be considered.

Request Pattern, Pre-Analytical and Analytical Conditions of Urinalysis in Primary Care: Lessons from a One-Year Large-Scale Multicenter Study.

PubMed

Salinas, Maria; Lopez-Garrigos, Maite; Flores, Emilio; Leiva-Salinas, Carlos

2018-06-01

To study the urinalysis request, pre-analytical sample conditions, and analytical procedures. Laboratories were asked to provide the number of primary care urinalyses requested, and to fill out a questionnaire regarding pre-analytical conditions and analytical procedures. 110 laboratories participated in the study. 232.5 urinalyses/1,000 inhabitants were reported. 75.4% used the first morning urine. The sample reached the laboratory in less than 2 hours in 18.8%, between 2 - 4 hours in 78.3%, and between 4 - 6 hours in the remaining 2.9%. 92.5% combined the use of test strip and particle analysis, and only 7.5% used the strip exclusively. All participants except one performed automated particle analysis depending on strip results; in 16.2% the procedure was only manual. Urinalysis was highly requested. There was a lack of compliance with guidelines regarding time between micturition and analysis that usually involved the combination of strip followed by particle analysis.

Variability in, variability out: best practice recommendations to standardize pre-analytical variables in the detection of circulating and tissue microRNAs.

PubMed

Khan, Jenna; Lieberman, Joshua A; Lockwood, Christina M

2017-05-01

microRNAs (miRNAs) hold promise as biomarkers for a variety of disease processes and for determining cell differentiation. These short RNA species are robust, survive harsh treatment and storage conditions and may be extracted from blood and tissue. Pre-analytical variables are critical confounders in the analysis of miRNAs: we elucidate these and identify best practices for minimizing sample variation in blood and tissue specimens. Pre-analytical variables addressed include patient-intrinsic variation, time and temperature from sample collection to storage or processing, processing methods, contamination by cells and blood components, RNA extraction method, normalization, and storage time/conditions. For circulating miRNAs, hemolysis and blood cell contamination significantly affect profiles; samples should be processed within 2 h of collection; ethylene diamine tetraacetic acid (EDTA) is preferred while heparin should be avoided; samples should be "double spun" or filtered; room temperature or 4 °C storage for up to 24 h is preferred; miRNAs are stable for at least 1 year at -20 °C or -80 °C. For tissue-based analysis, warm ischemic time should be <1 h; cold ischemic time (4 °C) <24 h; common fixative used for all specimens; formalin fix up to 72 h prior to processing; enrich for cells of interest; validate candidate biomarkers with in situ visualization. Most importantly, all specimen types should have standard and common workflows with careful documentation of relevant pre-analytical variables.

MALDI-TOF MS identification of anaerobic bacteria: assessment of pre-analytical variables and specimen preparation techniques.

PubMed

Hsu, Yen-Michael S; Burnham, Carey-Ann D

2014-06-01

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a tool for identifying clinically relevant anaerobes. We evaluated the analytical performance characteristics of the Bruker Microflex with Biotyper 3.0 software system for identification of anaerobes and examined the impact of direct formic acid (FA) treatment and other pre-analytical factors on MALDI-TOF MS performance. A collection of 101 anaerobic bacteria were evaluated, including Clostridium spp., Propionibacterium spp., Fusobacterium spp., Bacteroides spp., and other anaerobic bacterial of clinical relevance. The results of our study indicate that an on-target extraction with 100% FA improves the rate of accurate identification without introducing misidentification (P<0.05). In addition, we modify the reporting cutoffs for the Biotyper "score" yielding acceptable identification. We found that a score of ≥1.700 can maximize the rate of identification. Of interest, MALDI-TOF MS can correctly identify anaerobes grown in suboptimal conditions, such as on selective culture media and following oxygen exposure. In conclusion, we report on a number of simple and cost-effective pre- and post-analytical modifications could enhance MALDI-TOF MS identification for anaerobic bacteria. Copyright © 2014 Elsevier Inc. All rights reserved.

Management of thyroid cytological material, pre-analytical procedures and bio-banking.

PubMed

Bode-Lesniewska, Beata; Cochand-Priollet, Beatrix; Straccia, Patrizia; Fadda, Guido; Bongiovanni, Massimo

2018-06-09

Thyroid nodules are common and increasingly detected due to recent advances in imaging techniques. However, clinically relevant thyroid cancer is rare and the mortality from aggressive thyroid cancer remains constant. FNAC (Fine Needle Aspiration Cytology) is a standard method for diagnosing thyroid malignancy and the discrimination of malignant nodules from goiter. As the examined nodules on thyroid FNAC are often small incidental findings, it is important to maintain a low rate of undetermined diagnoses requiring further clinical work up or surgery. The most important factors determining the accuracy of the cytological diagnosis and suitability for biobanking of thyroid FNACs are the quality of the sample and availability of adequate tissue for auxiliary studies. This article analyses technical aspects (pre-analytics) of performing thyroid FNACs, including image guidance and rapid on slide evaluation (ROSE), sample collection methods (conventional slides, liquid based methods (LBC), cell blocks) and storage (bio-banking). The spectrum of the special studies (immunocytochemistry on direct slides or LBC, immunohistochemistry on cell blocks and molecular methods) required for improving the precision of the cytological diagnosis of the thyroid nodules is discussed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Gulf Long-Term Follow-Up Study (GuLF STUDY): Biospecimen collection at enrollment.

PubMed

Engel, Lawrence S; Kwok, Richard K; Miller, Aubrey K; Blair, Aaron; Curry, Matthew D; McGrath, John A; Sandler, Dale P

2017-01-01

The 2010 Deepwater Horizon (DWH) explosion in the Gulf of Mexico led to the largest ever marine oil spill by volume. The GuLF STUDY is investigating possible adverse human health effects associated with oil spill activities. One objective of the study was to utilize biological specimens from study participants to examine spill-related adverse health effects. This study describes the methods for collecting, processing, shipping, and storing specimens during the enrollment phase of the study. GuLF STUDY participants living in Gulf States (Alabama, Florida, Louisiana, Mississippi, and eastern Texas) were eligible to complete a home visit at enrollment, one to three years after the DWH explosion. During this visit, blood, urine, toenail and hair clippings, and house dust samples were collected. Specimens were shipped overnight to a central processing laboratory in containers with cold and ambient temperature compartments. Most blood and urine specimens were then aliquoted and stored in liquid nitrogen vapor or at -80°C, with some samples stored at -20°C. A total of 11,193 participants completed a home visit, and over 99% provided at least one biospecimen. Most participants provided blood (93%), urine (99%), and toenail clippings (89%), and 40% provided hair. Nearly all participants (95%) provided house-dust samples. Most samples were received by the laboratory one (58%) or two (25%) days after collection. These biospecimens enable investigation of a range of biomarkers of spill-related adverse health effects, and possibly some biomarkers of spill-related exposures. The biospecimen collection, handling, and storage protocols were designed to maximize current and future scientific value within logistical and budgetary constraints and might serve as a template for future studies conducted in similar time-critical and geographically dispersed settings.

Creating a global rare disease patient registry linked to a rare diseases biorepository database: Rare Disease-HUB (RD-HUB).

PubMed

Rubinstein, Yaffa R; Groft, Stephen C; Bartek, Ronald; Brown, Kyle; Christensen, Ronald A; Collier, Elaine; Farber, Amy; Farmer, Jennifer; Ferguson, John H; Forrest, Christopher B; Lockhart, Nicole C; McCurdy, Kate R; Moore, Helen; Pollen, Geraldine B; Richesson, Rachel; Miller, Vanessa Rangel; Hull, Sara; Vaught, Jim

2010-09-01

A movement to create a global patient registry for as many as 7,000 rare diseases was launched at a workshop, "Advancing Rare Disease Research: The Intersection of Patient Registries, Biospecimen Repositories, and Clinical Data." http://rarediseases.info.nih.gov/PATIENT_REGISTRIES_WORKSHOP/. The workshop was sponsored by the Office of Rare Diseases Research (ORDR). The focus was the building of an infrastructure for an internet-based global registry linking to biorepositories. Such a registry would serve the patients, investigators, and drug companies. To aid researchers the participants suggested the creation of a centralized database of biorepositories for rare biospecimens (RD-HUB)http://biospecimens.ordr.info.nih.gov/ that could be linked to the registry. Over two days of presentations and breakout sessions, several hundred attendees discussed government rules and regulations concerning privacy and patients' rights and the nature and scope of data to be entered into a central registry as well as concerns about how to validate patient and clinician-entered data to ensure data accuracy. Mechanisms for aggregating data from existing registries were also discussed. The attendees identified registry best practices, model coding systems, international systems for recruiting patients into clinical trials and novel ways of using the internet directly to invite participation in research. They also speculated about who would bear ultimate responsibility for the informatics in the registry and who would have access to the information. Hurdles associated with biospecimen collection and how to overcome them were detailed. The development of the recommendations was, in itself, an indication of the commitment of the rare disease community as never before. Published by Elsevier Inc.

The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort

PubMed Central

Goldman, Jennifer G.; Alcalay, Roy N.; Xie, Tao; Tuite, Paul; Henchcliffe, Claire; Hogarth, Penelope; Amara, Amy W.; Frank, Samuel; Rudolph, Alice; Casaceli, Cynthia; Andrews, Howard; Gwinn, Katrina; Sutherland, Margaret; Kopil, Catherine; Vincent, Lona; Frasier, Mark

2016-01-01

ABSTRACT Background Identifying PD‐specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, variability of collection protocols, and focus on de novo, unmedicated patients. Thus, a platform for biomarker discovery and validation in well‐characterized, clinically typical, moderate to advanced PD cohorts is critically needed. Methods BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease) is a cross‐sectional, multicenter biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva, and urine samples from 118 moderate to advanced PD and 88 healthy control subjects. Inclusion criteria were designed to maximize diagnostic specificity by selecting participants with clinically typical PD symptoms, and clinical data and biospecimen collection utilized standardized procedures to minimize variability across sites. Results We present the study methodology and data on the cohort's clinical characteristics. Motor scores and biospecimen samples including plasma are available for practically defined off and on states and thus enable testing the effects of PD medications on biomarkers. Other biospecimens are available from off state PD assessments and from controls. Conclusion Our cohort provides a valuable resource for biomarker discovery and validation in PD. Clinical data and biospecimens, available through The Michael J. Fox Foundation for Parkinson's Research and the National Institute of Neurological Disorders and Stroke, can serve as a platform for discovering biomarkers in clinically typical PD and comparisons across PD's broad and heterogeneous spectrum. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:27113479

Community Perceptions of Biobanking Participation: A Qualitative Study among Mexican-Americans in Three Texas Cities.

PubMed

Heredia, Natalia I; Krasny, Sarah; Strong, Larkin L; Von Hatten, Laura; Nguyen, Lynne; Reininger, Belinda M; McNeill, Lorna H; Fernández, María E

2017-01-01

Most biospecimens in the US are collected from non-Hispanic Whites, limiting the generalizability of findings. There is a need to increase participation in biobanking among ethnic and racial minorities. The purpose of this study was to use qualitative methods to identify factors that may influence Mexican-American individuals' willingness to participate in biobanking. We conducted 15 focus groups in three Texas cities with Mexican-American individuals, in both Spanish and English. Lack of knowledge about medical research and biobanks, lack of information about the specifics of biobanking participation, lack of communication of the results, fear of pain or harm, and distrust of the healthcare system or health research were identified as barriers to biobanking participation. Facilitators to participation were altruism, safety, understanding biobanking procedures and purposes, perceived benefits to participation, and culturally appropriate recruitment strategies. Although Mexican-Americans living in Texas are willing to donate biospecimens for altruistic reasons, such as helping society or advancing science, they want more information about what biobanking entails. They want to be assured that participation will not cause them harm and that the research is conducted with good intentions. Results from this study can inform educational materials or interventions to increase Hispanic participation in biobanking. © 2016 S. Karger AG, Basel.

Community perceptions of biobanking participation: A qualitative study among Mexican-Americans in three Texas cities

PubMed Central

Heredia, Natalia I.; Krasny, Sarah; Strong, Larkin L.; Von Hatten, Laura; Nguyen, Lynne; Reininger, Belinda M.; McNeill, Lorna H.; Fernández, María E.

2016-01-01

Background Most biospecimens in the U.S. are collected from Non-Hispanic Whites, limiting the generalizability of findings. There is a need to increase participation in biobanking among ethnic and racial minorities. The purpose of this study was to use qualitative methods to identify factors that may influence Mexican-American individuals’ willingness to participate in biobanking. Methods We conducted 15 focus groups in three Texas cities with Mexican-American individuals, in both Spanish and English. Results Lack of knowledge about medical research and biobanks, lack of information about the specifics of biobanking participation, lack of communication of the results, fear of pain or harm, and distrust of the healthcare system or health research were identified as barriers to biobanking participation. Facilitators to participation were altruism, safety, understanding biobanking procedures and purposes, perceived benefits to participation, and culturally-appropriate recruitment strategies. Although Mexican-Americans living in Texas are willing to donate biospecimens for altruistic reasons, such as helping society or advancing science, they want more information about what biobanking entails. They want to be assured that participation will not cause them harm, and that the research is conducted with good intentions. Conclusion Results from this study can inform educational materials or interventions to increase Hispanic participation in biobanking. PMID:27926908

Strategies for improving the collection of 24-hour urine for analysis in the clinical laboratory: redesigned instructions, opinion surveys, and application of reference change value to micturition.

PubMed

Tormo, Consuelo; Lumbreras, Blanca; Santos, Ana; Romero, Luis; Conca, Minerva

2009-12-01

-The preanalytic phase of 24-hour urine collection, before clinical analysis, requires the active participation of patients and usually takes place outside the laboratory. -We verify whether distribution of adequate information to health care personnel and patients will result in fewer preanalytic incidents. We also determine the intraindividual biologic variability associated with micturition and the corresponding reference change value (RCV). -The intervention provided training for 24-hour urine collection to the health care personnel of the 20th health district of the Valencian community in Spain. The preanalytic incidents related to 24-hour micturition were estimated before and after the intervention. An opinion survey on the problems involved in urine collection was also conducted among patients. The Harris formula was used to calculate the RCV. -Before the intervention, 130 preanalytic incidents were recorded (11.5%) and after the intervention, 76 (8.6%) (P = .04) were recorded. Of the 130 incidents recorded before the intervention, 63 (48.5%) involved omission to indicate the urine volume, and of the 76 incidents recorded after the intervention, only 1 (1.3%) (P < .001) involved this omission. Forty of 302 patients (13.2%) surveyed reported problems and more than half (175; 57.9%) had to collect various urine samples sequentially. The RCV determined was 54.5% for a percentage of variation in volume of 24-hour urine (PVVI) of 19.0 +/- 16.5%. Therefore, micturition associated with a PVVI >+/-54.5% suggests that 24-hour urine collection by the patient was incomplete. The results obtained when applying the RCV after the intervention showed that 6.3% of the 24-hour urine samples should be rejected. -The percentage of preanalytic incidents was reduced by providing health care personnel with information and training. The percentage of variation in volume of 24-hour urine can be used to evaluate the variation in patients' micturition. Reference change value was shown to be useful when determining whether 24-hour urine was properly collected.

Advancing Translational Space Research Through Biospecimen Sharing: Amplifying the Impact of Ground-Based Studies

NASA Technical Reports Server (NTRS)

Ronca, A.; Lewis, L.; Staten, B.; Moyer, E.; Vizir, V.; Gompf, H.; Hoban-Higgins, T.; Fuller, C. A.

2017-01-01

Biospecimen Sharing Programs (BSPs) have been organized by NASA Ames Research Center since the 1960s with the goal of maximizing utilization and scientific return from rare, complex and costly spaceflight experiments. BSPs involve acquiring otherwise unused biological specimens from primary space research experiments for distribution to secondary experiments. Here we describe a collaboration leveraging Ames expertise in biospecimen sharing to magnify the scientific impact of research informing astronaut health funded by the NASA Human Research Program (HRP) Human Health Countermeasures (HHC) Element. The concept expands biospecimen sharing to one-off ground-based studies utilizing analogue space platforms (e.g., Hind limb Unloading (HLU), Artificial Gravity) for rodent experiments, thereby significantly broadening the range of research opportunities with translational relevance for protecting human health in space and on Earth. In this presentation, we will report on biospecimens currently being acquired from HHC Award Head-Down Tilt as a Model for Intracranial and Intraocular Pressures, and Retinal Changes during Spaceflight, and their availability. The BSP add-on to the project described herein has already yielded for HHC-funded investigators more than 4,700 additional tissues that would otherwise have been discarded as waste, with additional tissues available for analysis. Young (3-mo old) male and female rats and Older (9-mo old) male rats are being exposed to HLU for either 7, 14, 28, or 90 days. Additional groups are exposed to 90 days of unloading followed by either 7, 14, 28 days or 90 days of recovery (normal loading). Comparisons are made with non-suspended controls. Unused tissues are: Skin, Lungs, Thymus, Adrenals, Kidneys, Spleen, Hindlimb Muscles (Soleus, Extensor Digitorum Longus, Tibialis Anterior, Plantaris Gastrocnemius), Fat Pads, Reproductive Organs, and Intestines. Tissues are harvested, weighed, preserved then archived (with metadata) using a sample tracking system (CryoTrack). Preservation techniques include snap-freezing and RNALatersnap-freezing. Specimens were weighed at the time of dissection, and organ mass: body mass ratios analyzed to determine unloading effects across conditions and durations. The results corroborate previously reported effects of short-term exposure to microgravity or unloading exposure on various organs, and provide new insights into adaptation to long-duration unloading relevant to sustained spaceflight exposures on ISS. Supported by the Human Research Program (HRP) Human Health Countermeasures (HHC) Element and NASA Grant NNX13AD94G (CAF).

Impact of Educational Activities in Reducing Pre-Analytical Laboratory Errors

PubMed Central

Al-Ghaithi, Hamed; Pathare, Anil; Al-Mamari, Sahimah; Villacrucis, Rodrigo; Fawaz, Naglaa; Alkindi, Salam

2017-01-01

Objectives Pre-analytic errors during diagnostic laboratory investigations can lead to increased patient morbidity and mortality. This study aimed to ascertain the effect of educational nursing activities on the incidence of pre-analytical errors resulting in non-conforming blood samples. Methods This study was conducted between January 2008 and December 2015. All specimens received at the Haematology Laboratory of the Sultan Qaboos University Hospital, Muscat, Oman, during this period were prospectively collected and analysed. Similar data from 2007 were collected retrospectively and used as a baseline for comparison. Non-conforming samples were defined as either clotted samples, haemolysed samples, use of the wrong anticoagulant, insufficient quantities of blood collected, incorrect/lack of labelling on a sample or lack of delivery of a sample in spite of a sample request. From 2008 onwards, multiple educational training activities directed at the hospital nursing staff and nursing students primarily responsible for blood collection were implemented on a regular basis. Results After initiating corrective measures in 2008, a progressive reduction in the percentage of non-conforming samples was observed from 2009 onwards. Despite a 127.84% increase in the total number of specimens received, there was a significant reduction in non-conforming samples from 0.29% in 2007 to 0.07% in 2015, resulting in an improvement of 75.86% (P <0.050). In particular, specimen identification errors decreased by 0.056%, with a 96.55% improvement. Conclusion Targeted educational activities directed primarily towards hospital nursing staff had a positive impact on the quality of laboratory specimens by significantly reducing pre-analytical errors. PMID:29062553

Evaluation of analytical errors in a clinical chemistry laboratory: a 3 year experience.

PubMed

Sakyi, As; Laing, Ef; Ephraim, Rk; Asibey, Of; Sadique, Ok

2015-01-01

Proficient laboratory service is the cornerstone of modern healthcare systems and has an impact on over 70% of medical decisions on admission, discharge, and medications. In recent years, there is an increasing awareness of the importance of errors in laboratory practice and their possible negative impact on patient outcomes. We retrospectively analyzed data spanning a period of 3 years on analytical errors observed in our laboratory. The data covered errors over the whole testing cycle including pre-, intra-, and post-analytical phases and discussed strategies pertinent to our settings to minimize their occurrence. We described the occurrence of pre-analytical, analytical and post-analytical errors observed at the Komfo Anokye Teaching Hospital clinical biochemistry laboratory during a 3-year period from January, 2010 to December, 2012. Data were analyzed with Graph Pad Prism 5(GraphPad Software Inc. CA USA). A total of 589,510 tests was performed on 188,503 outpatients and hospitalized patients. The overall error rate for the 3 years was 4.7% (27,520/58,950). Pre-analytical, analytical and post-analytical errors contributed 3.7% (2210/58,950), 0.1% (108/58,950), and 0.9% (512/58,950), respectively. The number of tests reduced significantly over the 3-year period, but this did not correspond with a reduction in the overall error rate (P = 0.90) along with the years. Analytical errors are embedded within our total process setup especially pre-analytical and post-analytical phases. Strategic measures including quality assessment programs for staff involved in pre-analytical processes should be intensified.

Exploring the initial steps of the testing process: frequency and nature of pre-preanalytic errors.

PubMed

Carraro, Paolo; Zago, Tatiana; Plebani, Mario

2012-03-01

Few data are available on the nature of errors in the so-called pre-preanalytic phase, the initial steps of the testing process. We therefore sought to evaluate pre-preanalytic errors using a study design that enabled us to observe the initial procedures performed in the ward, from the physician's test request to the delivery of specimens in the clinical laboratory. After a 1-week direct observational phase designed to identify the operating procedures followed in 3 clinical wards, we recorded all nonconformities and errors occurring over a 6-month period. Overall, the study considered 8547 test requests, for which 15 917 blood sample tubes were collected and 52 982 tests undertaken. No significant differences in error rates were found between the observational phase and the overall study period, but underfilling of coagulation tubes was found to occur more frequently in the direct observational phase (P = 0.043). In the overall study period, the frequency of errors was found to be particularly high regarding order transmission [29 916 parts per million (ppm)] and hemolysed samples (2537 ppm). The frequency of patient misidentification was 352 ppm, and the most frequent nonconformities were test requests recorded in the diary without the patient's name and failure to check the patient's identity at the time of blood draw. The data collected in our study confirm the relative frequency of pre-preanalytic errors and underline the need to consensually prepare and adopt effective standard operating procedures in the initial steps of laboratory testing and to monitor compliance with these procedures over time.

Impact of Educational Activities in Reducing Pre-Analytical Laboratory Errors: A quality initiative.

PubMed

Al-Ghaithi, Hamed; Pathare, Anil; Al-Mamari, Sahimah; Villacrucis, Rodrigo; Fawaz, Naglaa; Alkindi, Salam

2017-08-01

Pre-analytic errors during diagnostic laboratory investigations can lead to increased patient morbidity and mortality. This study aimed to ascertain the effect of educational nursing activities on the incidence of pre-analytical errors resulting in non-conforming blood samples. This study was conducted between January 2008 and December 2015. All specimens received at the Haematology Laboratory of the Sultan Qaboos University Hospital, Muscat, Oman, during this period were prospectively collected and analysed. Similar data from 2007 were collected retrospectively and used as a baseline for comparison. Non-conforming samples were defined as either clotted samples, haemolysed samples, use of the wrong anticoagulant, insufficient quantities of blood collected, incorrect/lack of labelling on a sample or lack of delivery of a sample in spite of a sample request. From 2008 onwards, multiple educational training activities directed at the hospital nursing staff and nursing students primarily responsible for blood collection were implemented on a regular basis. After initiating corrective measures in 2008, a progressive reduction in the percentage of non-conforming samples was observed from 2009 onwards. Despite a 127.84% increase in the total number of specimens received, there was a significant reduction in non-conforming samples from 0.29% in 2007 to 0.07% in 2015, resulting in an improvement of 75.86% ( P <0.050). In particular, specimen identification errors decreased by 0.056%, with a 96.55% improvement. Targeted educational activities directed primarily towards hospital nursing staff had a positive impact on the quality of laboratory specimens by significantly reducing pre-analytical errors.

The Breast Cancer Family Registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer

PubMed Central

John, Esther M; Hopper, John L; Beck, Jeanne C; Knight, Julia A; Neuhausen, Susan L; Senie, Ruby T; Ziogas, Argyrios; Andrulis, Irene L; Anton-Culver, Hoda; Boyd, Norman; Buys, Saundra S; Daly, Mary B; O'Malley, Frances P; Santella, Regina M; Southey, Melissa C; Venne, Vickie L; Venter, Deon J; West, Dee W; Whittemore, Alice S; Seminara, Daniela

2004-01-01

Introduction The etiology of familial breast cancer is complex and involves genetic and environmental factors such as hormonal and lifestyle factors. Understanding familial aggregation is a key to understanding the causes of breast cancer and to facilitating the development of effective prevention and therapy. To address urgent research questions and to expedite the translation of research results to the clinical setting, the National Cancer Institute (USA) supported in 1995 the establishment of a novel research infrastructure, the Breast Cancer Family Registry, a collaboration of six academic and research institutions and their medical affiliates in the USA, Canada, and Australia. Methods The sites have developed core family history and epidemiology questionnaires, data dictionaries, and common protocols for biospecimen collection and processing and pathology review. An Informatics Center has been established to collate, manage, and distribute core data. Results As of September 2003, 9116 population-based and 2834 clinic-based families have been enrolled, including 2346 families from minority populations. Epidemiology questionnaire data are available for 6779 affected probands (with a personal history of breast cancer), 4116 unaffected probands, and 16,526 relatives with or without a personal history of breast or ovarian cancer. The biospecimen repository contains blood or mouthwash samples for 6316 affected probands, 2966 unaffected probands, and 10,763 relatives, and tumor tissue samples for 4293 individuals. Conclusion This resource is available to internal and external researchers for collaborative, interdisciplinary, and translational studies of the genetic epidemiology of breast cancer. Detailed information can be found at the URL . PMID:15217505

Lung Cancer and Chronic Obstructive Pulmonary Disease: Needs and Opportunities for Integrated Research

PubMed Central

Szabo, Eva; Croxton, Thomas L.; Shapiro, Steven D.; Dubinett, Steven M.

2009-01-01

Lung cancer and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality in the United States and worldwide. They share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by the incidence of these diseases in only a fraction of smokers. The presence of COPD increases the risk of lung cancer up to 4.5-fold. To investigate commonalities in disease mechanisms and perspectives for disease chemoprevention, the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) held a workshop. The participants identified four research objectives: 1) clarify common epidemiological characteristics of lung cancer and COPD; 2) identify shared genetic and epigenetic risk factors; 3) identify and validate biomarkers, molecular signatures, and imaging-derived measurements of each disease; and 4) determine common and disparate pathogenetic mechanisms. These objectives should be reached via four research approaches: 1) identify, publicize, and enable the evaluation and analysis of existing datasets and repositories of biospecimens; 2) obtain phenotypic and outcome data and biospecimens from large studies of subjects with and/or at risk for COPD and lung cancer; 3) develop and use animal and other preclinical models to investigate pathogenetic links between the diseases; and 4) conduct early-phase clinical trials of potential chemopreventive agents. To foster much needed research interactions, two final recommendations were made by the participants: 1) incorporate baseline phenotyping and outcome measures for both diseases in future longitudinal studies of each disease and 2) expand collaborative efforts between the NCI and NHLBI. PMID:19351920

Evaluation of Analytical Errors in a Clinical Chemistry Laboratory: A 3 Year Experience

PubMed Central

Sakyi, AS; Laing, EF; Ephraim, RK; Asibey, OF; Sadique, OK

2015-01-01

Background: Proficient laboratory service is the cornerstone of modern healthcare systems and has an impact on over 70% of medical decisions on admission, discharge, and medications. In recent years, there is an increasing awareness of the importance of errors in laboratory practice and their possible negative impact on patient outcomes. Aim: We retrospectively analyzed data spanning a period of 3 years on analytical errors observed in our laboratory. The data covered errors over the whole testing cycle including pre-, intra-, and post-analytical phases and discussed strategies pertinent to our settings to minimize their occurrence. Materials and Methods: We described the occurrence of pre-analytical, analytical and post-analytical errors observed at the Komfo Anokye Teaching Hospital clinical biochemistry laboratory during a 3-year period from January, 2010 to December, 2012. Data were analyzed with Graph Pad Prism 5(GraphPad Software Inc. CA USA). Results: A total of 589,510 tests was performed on 188,503 outpatients and hospitalized patients. The overall error rate for the 3 years was 4.7% (27,520/58,950). Pre-analytical, analytical and post-analytical errors contributed 3.7% (2210/58,950), 0.1% (108/58,950), and 0.9% (512/58,950), respectively. The number of tests reduced significantly over the 3-year period, but this did not correspond with a reduction in the overall error rate (P = 0.90) along with the years. Conclusion: Analytical errors are embedded within our total process setup especially pre-analytical and post-analytical phases. Strategic measures including quality assessment programs for staff involved in pre-analytical processes should be intensified. PMID:25745569

Pre-Test and Post-Test Applications to Shape the Education of Phlebotomists in A Quality Management Program: An Experience in a Training Hospital

PubMed Central

Keşapli, Mustafa; Aydin, Özgür; Esen, Hatice; Yeğin, Ayşenur; Güngör, Faruk; Yilmaz, Necat

2016-01-01

Summary Background After the introduction of modern laboratory instruments and information systems, preanalytic phase is the new field of battle. Errors in preanalytical phase account for approximately half of total errors in clinical laboratory. The objective of this study was to share an experience of an education program that was believed to be successful in decreasing the number of rejected samples received from the Emergency Department (ED). Methods An education program about laboratory procedures, quality requirements in the laboratory, patient and health-care worker safety was planned by the quality team to be performed on 36 people who were responsible for sample collection in the ED. A questionary which included 11 questions about the preanalytic phase was applied to all the attendees before and after training. The number of rejected samples per million was discovered with right proportion account over the number of accepted and rejected samples to laboratory after and before the training period. Results Most of the attendees were nurses (n: 22/55%), with over 12 years of experience in general and 2–4 years experience in the ED. Knowledge level of the attendees was calculated before training as 58.9% and after training as 91.8%. While the total rate of sample rejection before training was 2.35% (sigma value 3.37–3.50), the rate after training was 1.56% (sigma value 3.62–3.75). Conclusions Increasing the knowledge of staff has a direct positive impact on the preanalytic phase. The application of a pre-test was observed to be a feasible tool to shape group specific education programs. PMID:28356887

Pre-Test and Post-Test Applications to Shape the Education of Phlebotomists in A Quality Management Program: An Experience in a Training Hospital.

PubMed

Aykal, Güzin; Keşapli, Mustafa; Aydin, Özgür; Esen, Hatice; Yeğin, Ayşenur; Güngör, Faruk; Yilmaz, Necat

2016-09-01

After the introduction of modern laboratory instruments and information systems, preanalytic phase is the new field of battle. Errors in preanalytical phase account for approximately half of total errors in clinical laboratory. The objective of this study was to share an experience of an education program that was believed to be successful in decreasing the number of rejected samples received from the Emergency Department (ED). An education program about laboratory procedures, quality requirements in the laboratory, patient and health-care worker safety was planned by the quality team to be performed on 36 people who were responsible for sample collection in the ED. A questionary which included 11 questions about the preanalytic phase was applied to all the attendees before and after training. The number of rejected samples per million was discovered with right proportion account over the number of accepted and rejected samples to laboratory after and before the training period. Most of the attendees were nurses (n: 22/55%), with over 12 years of experience in general and 2-4 years experience in the ED. Knowledge level of the attendees was calculated before training as 58.9% and after training as 91.8%. While the total rate of sample rejection before training was 2.35% (sigma value 3.37-3.50), the rate after training was 1.56% (sigma value 3.62-3.75). Increasing the knowledge of staff has a direct positive impact on the preanalytic phase. The application of a pre-test was observed to be a feasible tool to shape group specific education programs.

Dried blood spot specimen quality and validation of a new pre-analytical processing method for qualitative HIV-1 PCR, KwaZulu-Natal, South Africa

PubMed Central

Parboosing, Raveen; Siyaca, Ntombizandile; Moodley, Pravikrishnen

2016-01-01

Background Poor quality dried blood spot (DBS) specimens are usually rejected by virology laboratories, affecting early infant diagnosis of HIV. The practice of combining two incompletely-filled DBS in one specimen preparation tube during pre-analytical specimen processing (i.e., the two-spot method) has been implemented to reduce the number of specimens being rejected for insufficient volume. Objectives This study analysed laboratory data to describe the quality of DBS specimens and the use of the two-spot method over a one-year period, then validated the two-spot method against the standard (one-spot) method. Methods Data on HIV-1 PCR test requests submitted in 2014 to the Department of Virology at Inkosi Albert Luthuli Central Hospital in KwaZulu-Natal province, South Africa were analysed to describe reasons for specimen rejection, as well as results of the two-spot method. The accuracy, lower limit of detection and precision of the two-spot method were assessed. Results Of the 88 481 specimens received, 3.7% were rejected for pre-analytical problems. Of those, 48.9% were rejected as a result of insufficient specimen volume. Two health facilities had significantly more specimen rejections than other facilities. The two-spot method prevented 10 504 specimen rejections. The Pearson correlation coefficient comparing the standard to the two-spot method was 0.997. Conclusions The two-spot method was comparable with the standard method of pre-analytical specimen processing. Two health facilities were identified for targeted retraining on specimen quality. The two-spot method of DBS specimen processing can be used as an adjunct to retraining, to reduce the number of specimens rejected and improve linkage to care. PMID:28879108

Dried blood spot specimen quality and validation of a new pre-analytical processing method for qualitative HIV-1 PCR, KwaZulu-Natal, South Africa.

PubMed

Govender, Kerusha; Parboosing, Raveen; Siyaca, Ntombizandile; Moodley, Pravikrishnen

2016-01-01

Poor quality dried blood spot (DBS) specimens are usually rejected by virology laboratories, affecting early infant diagnosis of HIV. The practice of combining two incompletely-filled DBS in one specimen preparation tube during pre-analytical specimen processing (i.e., the two-spot method) has been implemented to reduce the number of specimens being rejected for insufficient volume. This study analysed laboratory data to describe the quality of DBS specimens and the use of the two-spot method over a one-year period, then validated the two-spot method against the standard (one-spot) method. Data on HIV-1 PCR test requests submitted in 2014 to the Department of Virology at Inkosi Albert Luthuli Central Hospital in KwaZulu-Natal province, South Africa were analysed to describe reasons for specimen rejection, as well as results of the two-spot method. The accuracy, lower limit of detection and precision of the two-spot method were assessed. Of the 88 481 specimens received, 3.7% were rejected for pre-analytical problems. Of those, 48.9% were rejected as a result of insufficient specimen volume. Two health facilities had significantly more specimen rejections than other facilities. The two-spot method prevented 10 504 specimen rejections. The Pearson correlation coefficient comparing the standard to the two-spot method was 0.997. The two-spot method was comparable with the standard method of pre-analytical specimen processing. Two health facilities were identified for targeted retraining on specimen quality. The two-spot method of DBS specimen processing can be used as an adjunct to retraining, to reduce the number of specimens rejected and improve linkage to care.

Contrasting the ethical perspectives of biospecimen research among individuals with familial risk for hereditary cancer and biomedical researchers: implications for researcher training.

PubMed

Quinn, Gwendolyn P; Koskan, Alexis; Sehovic, Ivana; Pal, Tuya; Meade, Cathy; Gwede, Clement K

2014-07-01

While ethical concerns about participating in biospecimen research have been previously identified, few studies have reported the concerns among individuals with familial risk for hereditary cancer (IFRs). At the same time, biomedical researchers often lack training in discussing such concerns to potential donors. This study explores IFRs' and biomedical researchers' perceptions of ethical concerns about participating in biobanking research. In separate focus groups, IFRs and biomedical researchers participated in 90-min telephone focus groups. Focus group questions centered on knowledge about laws that protect the confidentiality of biospecimen donors, understanding of informed consent and study procedures, and preferences for being recontacted about potential incidental discovery and also study results. A total of 40 IFRs and 32 biomedical researchers participated in the focus groups. Results demonstrated discrepancies between the perceptions of IFRs and researchers. IFRs' concerns centered on health information protection; potential discrimination by insurers and employers; and preferences for being recontacted upon discovery of gene mutations or to communicate study results. Researchers perceived that participants understood laws protecting donors' privacy and (detailed study information outlined in the informed consent process), study outcomes were used to create a training tool kit to increase researchers' understanding of IFRs' concerns about biobanking.

Contrasting the Ethical Perspectives of Biospecimen Research Among Individuals with Familial Risk for Hereditary Cancer and Biomedical Researchers: Implications for Researcher Training

PubMed Central

Koskan, Alexis; Sehovic, Ivana; Pal, Tuya; Meade, Cathy; Gwede, Clement K.

2014-01-01

While ethical concerns about participating in biospecimen research have been previously identified, few studies have reported the concerns among individuals with familial risk for hereditary cancer (IFRs). At the same time, biomedical researchers often lack training in discussing such concerns to potential donors. This study explores IFRs' and biomedical researchers' perceptions of ethical concerns about participating in biobanking research. In separate focus groups, IFRs and biomedical researchers participated in 90-min telephone focus groups. Focus group questions centered on knowledge about laws that protect the confidentiality of biospecimen donors, understanding of informed consent and study procedures, and preferences for being recontacted about potential incidental discovery and also study results. A total of 40 IFRs and 32 biomedical researchers participated in the focus groups. Results demonstrated discrepancies between the perceptions of IFRs and researchers. IFRs' concerns centered on health information protection; potential discrimination by insurers and employers; and preferences for being recontacted upon discovery of gene mutations or to communicate study results. Researchers perceived that participants understood laws protecting donors' privacy and (detailed study information outlined in the informed consent process), study outcomes were used to create a training tool kit to increase researchers' understanding of IFRs' concerns about biobanking. PMID:24786355

A tissue retrieval and postharvest processing regimen for rodent reproductive tissues compatible with long-term storage on the international space station and postflight biospecimen sharing program.

PubMed

Gupta, Vijayalaxmi; Holets-Bondar, Lesya; Roby, Katherine F; Enders, George; Tash, Joseph S

2015-01-01

Collection and processing of tissues to preserve space flight effects from animals after return to Earth is challenging. Specimens must be harvested with minimal time after landing to minimize postflight readaptation alterations in protein expression/translation, posttranslational modifications, and expression, as well as changes in gene expression and tissue histological degradation after euthanasia. We report the development of a widely applicable strategy for determining the window of optimal species-specific and tissue-specific posteuthanasia harvest that can be utilized to integrate into multi-investigator Biospecimen Sharing Programs. We also determined methods for ISS-compatible long-term tissue storage (10 months at -80°C) that yield recovery of high quality mRNA and protein for western analysis after sample return. Our focus was reproductive tissues. The time following euthanasia where tissues could be collected and histological integrity was maintained varied with tissue and species ranging between 1 and 3 hours. RNA quality was preserved in key reproductive tissues fixed in RNAlater up to 40 min after euthanasia. Postfixation processing was also standardized for safe shipment back to our laboratory. Our strategy can be adapted for other tissues under NASA's Biospecimen Sharing Program or similar multi-investigator tissue sharing opportunities.

The Establishment of an ISO Compliant Cancer Biobank for Jordan and its Neighboring Countries Through Knowledge Transfer and Training

PubMed Central

Barr, Martin; Souan, Lina; MacGabhann, Peadar; Müller, Jeanette; Al Ashhab, Maxim; Jasser, Mohammed; Hamza, Khetam; Al Hassoon, Sallam; Kuhn, Uwe; Infante, Daniela; Lawlor, Denise; Gately, Kathy; Amireh, Eyad; O'Byrne, Kenneth

2014-01-01

Research studies aimed at advancing cancer prevention, diagnosis, and treatment depend on a number of key resources, including a ready supply of high-quality annotated biospecimens from diverse ethnic populations that can be used to test new drugs, assess the validity of prognostic biomarkers, and develop tailor-made therapies. In November 2011, KHCCBIO was established at the King Hussein Cancer Center (KHCC) with the support of Seventh Framework Programme (FP7) funding from the European Union (khccbio.khcc.jo). KHCCBIO was developed for the purpose of achieving an ISO accredited cancer biobank through the collection, processing, and preservation of high-quality, clinically annotated biospecimens from consenting cancer patients, making it the first cancer biobank of its kind in Jordan. The establishment of a state-of-the-art, standardized biospecimen repository of matched normal and lung tumor tissue, in addition to blood components such as serum, plasma, and white blood cells, was achieved through the support and experience of its European partners, Trinity College Dublin, Biostór Ireland, and accelopment AG. To date, KHCCBIO along with its partners, have worked closely in establishing an ISO Quality Management System (QMS) under which the biobank will operate. A Quality Policy Manual, Validation, and Training plan have been developed in addition to the development of standard operating procedures (SOPs) for consenting policies on ethical issues, data privacy, confidentiality, and biobanking bylaws. SOPs have also been drafted according to best international practices and implemented for the donation, procurement, processing, testing, preservation, storage, and distribution of tissues and blood samples from lung cancer patients, which will form the basis for the procurement of other cancer types. KHCCBIO will be the first ISO accredited cancer biobank from a diverse ethnic Middle Eastern and North African population. It will provide a unique and valuable resource of high-quality human biospecimens and anonymized clinicopathological data to the cancer research communities world-wide. PMID:24620764

A decade of experience in the development and implementation of tissue banking informatics tools for intra and inter-institutional translational research

PubMed Central

Amin, Waqas; Singh, Harpreet; Pople, Andre K.; Winters, Sharon; Dhir, Rajiv; Parwani, Anil V.; Becich, Michael J.

2010-01-01

Context: Tissue banking informatics deals with standardized annotation, collection and storage of biospecimens that can further be shared by researchers. Over the last decade, the Department of Biomedical Informatics (DBMI) at the University of Pittsburgh has developed various tissue banking informatics tools to expedite translational medicine research. In this review, we describe the technical approach and capabilities of these models. Design: Clinical annotation of biospecimens requires data retrieval from various clinical information systems and the de-identification of the data by an honest broker. Based upon these requirements, DBMI, with its collaborators, has developed both Oracle-based organ-specific data marts and a more generic, model-driven architecture for biorepositories. The organ-specific models are developed utilizing Oracle 9.2.0.1 server tools and software applications and the model-driven architecture is implemented in a J2EE framework. Result: The organ-specific biorepositories implemented by DBMI include the Cooperative Prostate Cancer Tissue Resource (http://www.cpctr.info/), Pennsylvania Cancer Alliance Bioinformatics Consortium (http://pcabc.upmc.edu/main.cfm), EDRN Colorectal and Pancreatic Neoplasm Database (http://edrn.nci.nih.gov/) and Specialized Programs of Research Excellence (SPORE) Head and Neck Neoplasm Database (http://spores.nci.nih.gov/current/hn/index.htm). The model-based architecture is represented by the National Mesothelioma Virtual Bank (http://mesotissue.org/). These biorepositories provide thousands of well annotated biospecimens for the researchers that are searchable through query interfaces available via the Internet. Conclusion: These systems, developed and supported by our institute, serve to form a common platform for cancer research to accelerate progress in clinical and translational research. In addition, they provide a tangible infrastructure and resource for exposing research resources and biospecimen services in collaboration with the clinical anatomic pathology laboratory information system (APLIS) and the cancer registry information systems. PMID:20922029

A decade of experience in the development and implementation of tissue banking informatics tools for intra and inter-institutional translational research.

PubMed

Amin, Waqas; Singh, Harpreet; Pople, Andre K; Winters, Sharon; Dhir, Rajiv; Parwani, Anil V; Becich, Michael J

2010-08-10

Tissue banking informatics deals with standardized annotation, collection and storage of biospecimens that can further be shared by researchers. Over the last decade, the Department of Biomedical Informatics (DBMI) at the University of Pittsburgh has developed various tissue banking informatics tools to expedite translational medicine research. In this review, we describe the technical approach and capabilities of these models. Clinical annotation of biospecimens requires data retrieval from various clinical information systems and the de-identification of the data by an honest broker. Based upon these requirements, DBMI, with its collaborators, has developed both Oracle-based organ-specific data marts and a more generic, model-driven architecture for biorepositories. The organ-specific models are developed utilizing Oracle 9.2.0.1 server tools and software applications and the model-driven architecture is implemented in a J2EE framework. The organ-specific biorepositories implemented by DBMI include the Cooperative Prostate Cancer Tissue Resource (http://www.cpctr.info/), Pennsylvania Cancer Alliance Bioinformatics Consortium (http://pcabc.upmc.edu/main.cfm), EDRN Colorectal and Pancreatic Neoplasm Database (http://edrn.nci.nih.gov/) and Specialized Programs of Research Excellence (SPORE) Head and Neck Neoplasm Database (http://spores.nci.nih.gov/current/hn/index.htm). The model-based architecture is represented by the National Mesothelioma Virtual Bank (http://mesotissue.org/). These biorepositories provide thousands of well annotated biospecimens for the researchers that are searchable through query interfaces available via the Internet. These systems, developed and supported by our institute, serve to form a common platform for cancer research to accelerate progress in clinical and translational research. In addition, they provide a tangible infrastructure and resource for exposing research resources and biospecimen services in collaboration with the clinical anatomic pathology laboratory information system (APLIS) and the cancer registry information systems.

Technical pre-analytical effects on the clinical biochemistry of Atlantic salmon (Salmo salar L.).

PubMed

Braceland, M; Houston, K; Ashby, A; Matthews, C; Haining, H; Rodger, H; Eckersall, P D

2017-01-01

Clinical biochemistry has long been utilized in human and veterinary medicine as a vital diagnostic tool, but despite occasional studies showing its usefulness in monitoring health status in Atlantic salmon (Salmo salar L.), it has not yet been widely utilized within the aquaculture industry. This is due, in part, to a lack of an agreed protocol for collection and processing of blood prior to analysis. Moreover, while the analytical phase of clinical biochemistry is well controlled, there is a growing understanding that technical pre-analytical variables can influence analyte concentrations or activities. In addition, post-analytical interpretation of treatment effects is variable in the literature, thus making the true effect of sample treatment hard to evaluate. Therefore, a number of pre-analytical treatments have been investigated to examine their effect on analyte concentrations and activities. In addition, reference ranges for salmon plasma biochemical analytes have been established to inform veterinary practitioners and the aquaculture industry of the importance of clinical biochemistry in health and disease monitoring. Furthermore, a standardized protocol for blood collection has been proposed. © 2016 The Authors Journal of Fish Diseases Published by John Wiley & Sons Ltd.

Standard operating procedures for pre-analytical handling of blood and urine for metabolomic studies and biobanks.

PubMed

Bernini, Patrizia; Bertini, Ivano; Luchinat, Claudio; Nincheri, Paola; Staderini, Samuele; Turano, Paola

2011-04-01

(1)H NMR metabolic profiling of urine, serum and plasma has been used to monitor the impact of the pre-analytical steps on the sample quality and stability in order to propose standard operating procedures (SOPs) for deposition in biobanks. We analyzed the quality of serum and plasma samples as a function of the elapsed time (t = 0-4 h) between blood collection and processing and of the time from processing to freezing (up to 24 h). The stability of the urine metabolic profile over time (up to 24 h) at various storage temperatures was monitored as a function of the different pre-analytical treatments like pre-storage centrifugation, filtration, and addition of the bacteriostatic preservative sodium azide. Appreciable changes in the profiles, reflecting changes in the concentration of a number of metabolites, were detected and discussed in terms of chemical and enzymatic reactions for both blood and urine samples. Appropriate procedures for blood derivatives collection and urine preservation/storage that allow maintaining as much as possible the original metabolic profile of the fresh samples emerge, and are proposed as SOPs for biobanking.

Development and validation of dried matrix spot sampling for the quantitative determination of amyloid β peptides in cerebrospinal fluid.

PubMed

Delaby, Constance; Gabelle, Audrey; Meynier, Philippe; Loubiere, Vincent; Vialaret, Jérôme; Tiers, Laurent; Ducos, Jacques; Hirtz, Christophe; Lehmann, Sylvain

2014-05-01

The use of dried blood spots on filter paper is well documented as an affordable and practical alternative to classical venous sampling for various clinical needs. This technique has indeed many advantages in terms of collection, biological safety, storage, and shipment. Amyloid β (Aβ) peptides are useful cerebrospinal fluid (CSF) biomarkers for Alzheimer disease diagnosis. However, Aβ determination is hindered by preanalytical difficulties in terms of sample collection and stability in tubes. We compared the quantification of Aβ peptides (1-40, 1-42, and 1-38) by simplex and multiplex ELISA, following either a standard operator method (liquid direct quantification) or after spotting CSF onto dried matrix paper card. The use of dried matrix spot (DMS) overcame preanalytical problems and allowed the determination of Aβ concentrations that were highly commutable (Bland-Altman) with those obtained using CSF in classical tubes. Moreover, we found a positive and significant correlation (r2=0.83, Pearson coefficient p=0.0329) between the two approaches. This new DMS method for CSF represents an interesting alternative that increases the quality and efficiency in preanalytics. This should enable the better exploitation of Aβ analytes for Alzheimer's diagnosis.

Cancer pharmacogenomics and pharmacoepidemiology: setting a research agenda to accelerate translation.

PubMed

Freedman, Andrew N; Sansbury, Leah B; Figg, William D; Potosky, Arnold L; Weiss Smith, Sheila R; Khoury, Muin J; Nelson, Stefanie A; Weinshilboum, Richard M; Ratain, Mark J; McLeod, Howard L; Epstein, Robert S; Ginsburg, Geoffrey S; Schilsky, Richard L; Liu, Geoffrey; Flockhart, David A; Ulrich, Cornelia M; Davis, Robert L; Lesko, Lawrence J; Zineh, Issam; Randhawa, Gurvaneet; Ambrosone, Christine B; Relling, Mary V; Rothman, Nat; Xie, Heng; Spitz, Margaret R; Ballard-Barbash, Rachel; Doroshow, James H; Minasian, Lori M

2010-11-17

Recent advances in genomic research have demonstrated a substantial role for genomic factors in predicting response to cancer therapies. Researchers in the fields of cancer pharmacogenomics and pharmacoepidemiology seek to understand why individuals respond differently to drug therapy, in terms of both adverse effects and treatment efficacy. To identify research priorities as well as the resources and infrastructure needed to advance these fields, the National Cancer Institute (NCI) sponsored a workshop titled "Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation" on July 21, 2009, in Bethesda, MD. In this commentary, we summarize and discuss five science-based recommendations and four infrastructure-based recommendations that were identified as a result of discussions held during this workshop. Key recommendations include 1) supporting the routine collection of germline and tumor biospecimens in NCI-sponsored clinical trials and in some observational and population-based studies; 2) incorporating pharmacogenomic markers into clinical trials; 3) addressing the ethical, legal, social, and biospecimen- and data-sharing implications of pharmacogenomic and pharmacoepidemiologic research; and 4) establishing partnerships across NCI, with other federal agencies, and with industry. Together, these recommendations will facilitate the discovery and validation of clinical, sociodemographic, lifestyle, and genomic markers related to cancer treatment response and adverse events, and they will improve both the speed and efficiency by which new pharmacogenomic and pharmacoepidemiologic information is translated into clinical practice.

Genetic Testing and Tissue Banking for Personalized Oncology: Analytical and Institutional Factors

PubMed Central

Miles, George; Rae, James; Ramalingam, Suresh S.; Pfeifer, John

2016-01-01

Personalized oncology, or more aptly precision oncogenomics, refers to the identification and implementation of clinically actionable targets tailored to an individual patient’s cancer genomic information. Banking of human tissue and other biospecimens establishes a framework to extract and collect the data essential to our understanding of disease pathogenesis and treatment. Cancer cooperative groups in the United States have led the way in establishing robust biospecimen collection mechanisms to facilitate translational research, and combined with technological advances in molecular testing, tissue banking has expanded from its traditional base in academic research and is assuming an increasingly pivotal role in directing the clinical care of cancer patients. Comprehensive screening of tumors by DNA sequencing and the ability to mine and interpret these large data sets from well-organized tissue banks have defined molecular subtypes of cancer. Such stratification by genomic criteria has revolutionized our perspectives on cancer diagnosis and treatment, offering insight into prognosis, progression, and susceptibility or resistance to known therapeutic agents. In turn, this has enabled clinicians to offer treatments tailored to patients that can greatly improve their chances of survival. Unique challenges and opportunities accompany the rapidly evolving interplay between tissue banking and genomic sequencing, and are the driving forces underlying the revolution in precision medicine. Molecular testing and precision medicine clinical trials are now becoming the major thrust behind the cooperative groups’ clinical research efforts. PMID:26433552

Biobankonomics: developing a sustainable business model approach for the formation of a human tissue biobank.

PubMed

Vaught, Jimmie; Rogers, Joyce; Carolin, Todd; Compton, Carolyn

2011-01-01

The preservation of high-quality biospecimens and associated data for research purposes is being performed in variety of academic, government, and industrial settings. Often these are multimillion dollar operations, yet despite these sizable investments, the economics of biobanking initiatives is not well understood. Fundamental business principles must be applied to the development and operation of such resources to ensure their long-term sustainability and maximize their impact. The true costs of developing and maintaining operations, which may have a variety of funding sources, must be better understood. Among the issues that must be considered when building a biobank economic model are: understanding the market need for the particular type of biobank under consideration and understanding and efficiently managing the biobank's "value chain," which includes costs for case collection, tissue processing, storage management, sample distribution, and infrastructure and administration. By using these value chain factors, a Total Life Cycle Cost of Ownership (TLCO) model may be developed to estimate all costs arising from owning, operating, and maintaining a large centralized biobank. The TLCO approach allows for a better delineation of a biobank's variable and fixed costs, data that will be needed to implement any cost recovery program. This article represents an overview of the efforts made recently by the National Cancer Institute's Office of Biorepositories and Biospecimen Research as part of its effort to develop an appropriate cost model and cost recovery program for the cancer HUman Biobank (caHUB) initiative. All of these economic factors are discussed in terms of maximizing caHUB's potential for long-term sustainability but have broad applicability to the wide range of biobanking initiatives that currently exist.

[The taking and transport of biological samples].

PubMed

Kerwat, Klaus; Kerwat, Martina; Eberhart, Leopold; Wulf, Hinnerk

2011-05-01

The results of microbiological tests are the foundation for a targetted therapy and the basis for monitoring infections. The quality of each and every laboratory finding depends not only on an error-free analytical process. The pre-analysis handling procedures are of particular importance. They encompass all factors and influences prior to the actual analysis. These include the correct timepoint for sample taking, the packaging and the rapid transport of the material to be investigated. Errors in the pre-analytical processing are the most frequent reasons for inappropriate findings. © Georg Thieme Verlag Stuttgart · New York.

Challenges and Driving Forces for Business Plans in Biobanking.

PubMed

Macheiner, Tanja; Huppertz, Berthold; Bayer, Michaela; Sargsyan, Karine

2017-04-01

Due to increased utilization of biospecimens for research and emergence of new technologies, the availability and quality of biospecimens and their collection are coming more and more into focus. However, the long-term economic situation of biobanks is still mostly unclear. Also, the common sustainable utilization of various international biobanks is challenging due to local differences in sample processing, law and ethics. This article discusses possible strategies to achieve a sustainable utilization of biospecimens as part of the business plan of biobanks. The following questions were addressed as part of a business plan: (1) How can a biobank build up and maintain an up-to-date infrastructure? (2) What kind of funding can support the sustainability of a biobank? (3) Is there an international solution for informed consents to enable sample and data sharing? (4) How can a biobank react during economically unstable periods? (5) Which kind of biobanking research is innovative? (6) What kind of education could be most needful for knowledge transfer in biobanking? (7) Does an expiration date for a biobank make sense according to the period of funding? A strategy for optimal utilization begins with sharing of resources, infrastructure, and investments at the planning stage of a biobank, and continues to the transfer of knowledge and know-how by education. For clinical biobanks in particular, a long-term funding and cost recovery strategy is necessary for sustainable utilization.

Statistical Design for Biospecimen Cohort Size in Proteomics-based Biomarker Discovery and Verification Studies

PubMed Central

Skates, Steven J.; Gillette, Michael A.; LaBaer, Joshua; Carr, Steven A.; Anderson, N. Leigh; Liebler, Daniel C.; Ransohoff, David; Rifai, Nader; Kondratovich, Marina; Težak, Živana; Mansfield, Elizabeth; Oberg, Ann L.; Wright, Ian; Barnes, Grady; Gail, Mitchell; Mesri, Mehdi; Kinsinger, Christopher R.; Rodriguez, Henry; Boja, Emily S.

2014-01-01

Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC), with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance, and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step towards building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research. PMID:24063748

Statistical design for biospecimen cohort size in proteomics-based biomarker discovery and verification studies.

PubMed

Skates, Steven J; Gillette, Michael A; LaBaer, Joshua; Carr, Steven A; Anderson, Leigh; Liebler, Daniel C; Ransohoff, David; Rifai, Nader; Kondratovich, Marina; Težak, Živana; Mansfield, Elizabeth; Oberg, Ann L; Wright, Ian; Barnes, Grady; Gail, Mitchell; Mesri, Mehdi; Kinsinger, Christopher R; Rodriguez, Henry; Boja, Emily S

2013-12-06

Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor, and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC) with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step toward building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research.

Biospecimens | Division of Cancer Prevention

Cancer.gov

The PLCO Biorepository stores approximately 2.9 million biologic specimens collected from PLCO participants. Some of characteristics that make PLCO samples particularly valuable for etiologic and early marker research are: |

Quality Control of RNA Preservation and Extraction from Paraffin-Embedded Tissue: Implications for RT-PCR and Microarray Analysis

PubMed Central

Pichler, Martin; Zatloukal, Kurt

2013-01-01

Analysis of RNA isolated from fixed and paraffin-embedded tissues is widely used in biomedical research and molecular pathological diagnostics. We have performed a comprehensive and systematic investigation of the impact of factors in the pre-analytical workflow, such as different fixatives, fixation time, RNA extraction method and storage of tissues in paraffin blocks, on several downstream reactions including complementary DNA (cDNA) synthesis, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray hybridization. We compared the effects of routine formalin fixation with the non-crosslinking, alcohol-based Tissue Tek Xpress Molecular Fixative (TTXMF, Sakura Finetek), and cryopreservation as gold standard for molecular analyses. Formalin fixation introduced major changes into microarray gene expression data and led to marked gene-to-gene variations in delta-ct values of qRT-PCR. We found that qRT-PCR efficiency and gene-to-gene variations were mainly attributed to differences in the efficiency of cDNA synthesis as the most sensitive step. These differences could not be reliably detected by quality assessment of total RNA isolated from formalin-fixed tissues by electrophoresis or spectrophotometry. Although RNA from TTXMF fixed samples was as fragmented as RNA from formalin fixed samples, much higher cDNA yield and lower ct-values were obtained in qRT-PCR underlining the negative impact of crosslinking by formalin. In order to better estimate the impact of pre-analytical procedures such as fixation on the reliability of downstream analysis, we applied a qRT-PCR-based assay using amplicons of different length and an assay measuring the efficiency of cDNA generation. Together these two assays allowed better quality assessment of RNA extracted from fixed and paraffin-embedded tissues and should be used to supplement quality scores derived from automated electrophoresis. A better standardization of the pre-analytical workflow, application of additional quality controls and detailed sample information would markedly improve the comparability and reliability of molecular studies based on formalin-fixed and paraffin-embedded tissue samples. PMID:23936242

Evaluation of quality indicators in a laboratory supporting tertiary cancer care facilities in India.

PubMed

Kumar, Savitha Anil; Jayanna, Prashanth; Prabhudesai, Shilpa; Kumar, Ajai

2014-01-01

To collect and tabulate errors and nonconformities in the preanalytical, analytical, and postanalytical process phases in a diagnostic clinical laboratory that supports a super-specialty cancer center in India, and identify areas of potential improvement in patient services. We collected data from our laboratory during a period of 24 months. Departments in the study included clinical biochemistry, hematology, clinical pathology, microbiology and serology, surgical pathology, and molecular pathology. We had initiated quality assessment based on international standards in our laboratory in 2010, with the aim of obtaining accreditation by national and international governing bodies. We followed the guidelines specified by International Organization for Standardization (ISO) 15189:2007 to identify noncompliant elements of our processes. Among a total of 144,030 specimens that our referral laboratory received during the 2-year period of our study, we uncovered an overall error rate for all 3 process phases of 1.23%; all of our error rates closely approximated the results from our peer institutions. Errors were most common in the preanalytical phase in both years of study; preanalytical- and postanalytical-phase errors constituted more than 90% of all errors. Further improvements are warranted in laboratory services and are contingent on adequate training and interdepartmental communication and cooperation. Copyright© by the American Society for Clinical Pathology (ASCP).

Technical evaluation of the novel preanalytical module on instrumentation laboratory ACL TOP: advancing automation in hemostasis testing.

PubMed

Lippi, Giuseppe; Ippolito, Luigi; Favaloro, Emmanuel J

2013-10-01

Automation in hemostasis testing is entering an exciting and unprecedented phase. This study was planned to assess the performance of the new preanalytical module on the hemostasis testing system Instrumentation Laboratory ACL TOP. The evaluation included interference studies to define reliable thresholds for rejecting samples with significant concentrations of interfering substances; within-run imprecision studies of plasma indices on four different interference degrees for each index; comparison studies with reference measures of hemolysis index, bilirubin, and triglycerides on clinical chemistry analyzers; and calculation of turnaround time with and without automatic performance of preanalytical check. The upper limits for sample rejection according to our interference studies were 3.6 g/L for hemoglobin, 13.6 mg/dL for bilirubin, and 1454 mg/dL for triglycerides. We found optimal precision for all indices (0.6% to 3.1% at clinically relevant thresholds) and highly significant correlations with reference measures on clinical chemistry analyzers (from 0.985 to 0.998). The limited increase of turnaround time (i.e., +3% and +5% with or without cap-piercing), coupled with no adjunctive costs over performance of normal coagulation assays, contribute to make the automatic check of plasma indices on ACL TOP a reliable and practical approach for improving testing quality and safeguarding patient safety.

Need for gender-specific pre-analytical testing: the dark side of the moon in laboratory testing.

PubMed

Franconi, Flavia; Rosano, Giuseppe; Campesi, Ilaria

2015-01-20

Many international organisations encourage studies in a sex-gender perspective. However, research with a gender perspective presents a high degree of complexity, and the inclusion of sex-gender variable in experiments presents many methodological questions, the majority of which are still neglected. Overcoming these issues is fundamental to avoid erroneous results. Here, pre-analytical aspects of the research, such as study design, choice of utilised specimens, sample collection and processing, animal models of diseases, and the observer's role, are discussed. Artefacts in this stage of research could affect the predictive value of all analyses. Furthermore, the standardisation of research subjects according to their lifestyles and, if female, to their life phase and menses or oestrous cycle, is urgent to harmonise research worldwide. A sex-gender-specific attention to pre-analytical aspects could produce a decrease in the time for translation from the bench to bedside. Furthermore, sex-gender-specific pre-clinical pharmacological testing will enable adequate assessment of pharmacokinetic and pharmacodynamic actions of drugs and will enable, where appropriate, an adequate gender-specific clinical development plan. Therefore, sex-gender-specific pre-clinical research will increase the gender equity of care and will produce more evidence-based medicine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pre-analytical phase: The automated ProTube device supports quality assurance in the phlebotomy process.

PubMed

Piva, Elisa; Tosato, Francesca; Plebani, Mario

2015-12-07

Most errors in laboratory medicine occur in the pre-analytical phase of the total testing process. Phlebotomy, a crucial step in the pre-analytical phase influencing laboratory results and patient outcome, calls for quality assurance procedures and automation in order to prevent errors and ensure patient safety. We compared the performance of a new small, automated device, the ProTube Inpeco, designed for use in phlebotomy with a complete traceability of the process, with a centralized automated system, BC ROBO. ProTube was used for 15,010 patients undergoing phlebotomy with 48,776 tubes being labeled. The mean time and standard deviation (SD) for blood sampling was 3:03 (min:sec; SD ± 1:24) when using ProTube, against 5:40 (min:sec; SD ± 1:57) when using BC ROBO. The mean number of patients per hour managed at each phlebotomy point was 16 ± 3 with ProTube, and 10 ± 2 with BC ROBO. No tubes were labeled erroneously or incorrectly, even if process failure occurred in 2.8% of cases when ProTube was used. Thanks to its cutting edge technology, the ProTube has many advantages over BC ROBO, above all in verifying patient identity, and in allowing a reduction in both identification error and tube mislabeling.

Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

PubMed Central

Dietel, Manfred; Bubendorf, Lukas; Dingemans, Anne-Marie C; Dooms, Christophe; Elmberger, Göran; García, Rosa Calero; Kerr, Keith M; Lim, Eric; López-Ríos, Fernando; Thunnissen, Erik; Van Schil, Paul E; von Laffert, Maximilian

2016-01-01

Background There is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC. Methods Based on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned. The aim was to include all relevant aspects concerning NSCLC diagnosis. After careful consideration, the following topics were selected and each was reviewed by the experts: surgical resection and sampling; biopsy procedures for analysis; preanalytical and other variables affecting quality of tissue; tissue conservation; testing procedures for epidermal growth factor receptor, anaplastic lymphoma kinase and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) in lung tissue and cytological specimens; as well as standardised reporting and quality control (QC). Finally, an optimal workflow was described. Results Suggested optimal procedures and workflows are discussed in detail. The broad consensus was that the complex workflow presented can only be executed effectively by an interdisciplinary approach using a well-trained team. Conclusions To optimise diagnosis and treatment of patients with NSCLC, it is essential to establish SOPs that are adaptable to the local situation. In addition, a continuous QC system and a local multidisciplinary tumour-type-oriented board are essential. PMID:26530085

Analytical and pre-analytical performance characteristics of a novel cartridge-type blood gas analyzer for point-of-care and laboratory testing.

PubMed

Oyaert, Matthijs; Van Maerken, Tom; Bridts, Silke; Van Loon, Silvi; Laverge, Heleen; Stove, Veronique

2018-03-01

Point-of-care blood gas test results may benefit therapeutic decision making by their immediate impact on patient care. We evaluated the (pre-)analytical performance of a novel cartridge-type blood gas analyzer, the GEM Premier 5000 (Werfen), for the determination of pH, partial carbon dioxide pressure (pCO 2 ), partial oxygen pressure (pO 2 ), sodium (Na + ), potassium (K + ), chloride (Cl - ), ionized calcium ( i Ca 2+ ), glucose, lactate, and total hemoglobin (tHb). Total imprecision was estimated according to the CLSI EP5-A2 protocol. The estimated total error was calculated based on the mean of the range claimed by the manufacturer. Based on the CLSI EP9-A2 evaluation protocol, a method comparison with the Siemens RapidPoint 500 and Abbott i-STAT CG8+ was performed. Obtained data were compared against preset quality specifications. Interference of potential pre-analytical confounders on co-oximetry and electrolyte concentrations were studied. The analytical performance was acceptable for all parameters tested. Method comparison demonstrated good agreement to the RapidPoint 500 and i-STAT CG8+, except for some parameters (RapidPoint 500: pCO 2 , K + , lactate and tHb; i-STAT CG8+: pO 2 , Na + , i Ca 2+ and tHb) for which significant differences between analyzers were recorded. No interference of lipemia or methylene blue on CO-oximetry results was found. On the contrary, significant interference for benzalkonium and hemolysis on electrolyte measurements were found, for which the user is notified by an interferent specific flag. Identification of sample errors from pre-analytical sources, such as interferences and automatic corrective actions, along with the analytical performance, ease of use and low maintenance time of the instrument, makes the evaluated instrument a suitable blood gas analyzer for both POCT and laboratory use. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Impact of Pre-analytic Blood Sample Collection Factors on Metabolomics.

PubMed

Townsend, Mary K; Bao, Ying; Poole, Elizabeth M; Bertrand, Kimberly A; Kraft, Peter; Wolpin, Brian M; Clish, Clary B; Tworoger, Shelley S

2016-05-01

Many epidemiologic studies are using metabolomics to discover markers of carcinogenesis. However, limited data are available on the influence of pre-analytic blood collection factors on metabolite measurement. We quantified 166 metabolites in archived plasma from 423 Health Professionals Follow-up Study and Nurses' Health Study participants using liquid chromatography-tandem mass spectrometry (LC-MS). We compared multivariable-adjusted geometric mean metabolite LC-MS peak areas across fasting time, season of blood collection, and time of day of blood collection categories. The majority of metabolites (160 of 166 metabolites) had geometric mean peak areas that were within 15% comparing samples donated after fasting 9 to 12 versus ≥13 hours; greater differences were observed in samples donated after fasting ≤4 hours. Metabolite peak areas generally were similar across season of blood collection, although levels of certain metabolites (e.g., bile acids and purines/pyrimidines) tended to be different in the summer versus winter months. After adjusting for fasting status, geometric mean peak areas for bile acids and vitamins, but not other metabolites, differed by time of day of blood collection. Fasting, season of blood collection, and time of day of blood collection were not important sources of variability in measurements of most metabolites in our study. However, considering blood collection variables in the design or analysis of studies may be important for certain specific metabolites, particularly bile acids, purines/pyrimidines, and vitamins. These results may be useful for investigators formulating analysis plans for epidemiologic metabolomics studies, including determining which metabolites to a priori exclude from analyses. Cancer Epidemiol Biomarkers Prev; 25(5); 823-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Spanning the genomics era: the vital role of a single institution biorepository for childhood cancer research over a decade

PubMed Central

Zhou, Li

2015-01-01

The ‘genomics era’ is considered to have begun with the commencement of the Human Genome Project. As translational genomic studies can only be established when human tissue samples are available for analysis, biospecimens are now proven to be an essential element for their success. During the genomics era the necessity for more extensive biobanking infrastructure has been highlighted. With the increased number of genomic studies into cancer, it is considered that the availability of biospecimens will become the rate limiting step. Despite the efforts in international biobanking, translational genomics is hampered when there low numbers of biospecimens for a particular rare diseases and is most apparent for paediatric cancer. As there is a call for biobanking practice to be responsive to the current experimental needs of the time and for more expansive systems of tissue procurement to be established we have asked the question what role does a single institution biorepository play in the current highly networked world of translational genomics. Here we describe such a case. The Tumour Bank at The Children’s Hospital at Westmead (TB-CHW) in the western suburbs of Sydney was formally established in 1998 as a key resource for translational paediatric cancer research. During the genomics era, we show that the TB-CHW has developed into a key biospecimen repository for the cancer research community, during which time it has increasingly found itself having a vital role in the establishment of translational genomics for paediatric cancer. Here we detail metrics that demonstrate how as a single institution biorepository, the TB-CHW has been a strong participant in the advancement of translational genomics throughout the genomics era. This paper describes the significant contribution of a single institutional hospital embedded tumour biobank to the genomic research community. Despite the increased stringencies placed on biobanking practice, the TB-CHW has shown that a single institution biorespository can have a consistent and effective contribution to translational research into rare paediatric malignancy demonstrating its long term benefit throughout the genomics era. PMID:26835365

Flow cytometry for feline lymphoma: a retrospective study regarding pre-analytical factors possibly affecting the quality of samples.

PubMed

Martini, Valeria; Bernardi, Serena; Marelli, Priscilla; Cozzi, Marzia; Comazzi, Stefano

2018-06-01

Objectives Flow cytometry (FC) is becoming increasingly popular among veterinary oncologists for the diagnosis of lymphoma or leukaemia. It is accurate, fast and minimally invasive. Several studies of FC have been carried out in canine oncology and applied with great results, whereas there is limited knowledge and use of this technique in feline patients. This is mainly owing to the high prevalence of intra-abdominal lymphomas in this species and the difficulty associated with the diagnostic procedures needed to collect the sample. The purpose of the present study is to investigate whether any pre-analytical factor might affect the quality of suspected feline lymphoma samples for FC analysis. Methods Ninety-seven consecutive samples of suspected feline lymphoma were retrospectively selected from the authors' institution's FC database. The referring veterinarians were contacted and interviewed about several different variables, including signalment, appearance of the lesion, features of the sampling procedure and the experience of veterinarians performing the sampling. Statistical analyses were performed to assess the possible influence of these variables on the cellularity of the samples and the likelihood of it being finally processed for FC. Results Sample cellularity is a major factor in the likelihood of the sample being processed. Moreover, sample cellularity was significantly influenced by the needle size, with 21 G needles providing the highest cellularity. Notably, the sample cellularity and the likelihood of being processed did not vary between peripheral and intra-abdominal lesions. Approximately half of the cats required pharmacological restraint. Side effects were reported in one case only (transient swelling after peripheral lymph node sampling). Conclusions and relevance FC can be safely applied to cases of suspected feline lymphomas, including intra-abdominal lesions. A 21 G needle should be preferred for sampling. This study provides the basis for the increased use of this minimally invasive, fast and cost-effective technique in feline medicine.

CPTAC Prospective Biospecimen Collection Solicitation | Office of Cancer Clinical Proteomics Research

Cancer.gov

A new funding opportunity in support of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) seeks to prospectively procure tumor samples, collected for proteomics investigation.

Grantee Spotlight: Elisa Rodriguez, Ph.D., M.S.

Cancer.gov

Dr. Elisa M. Rodriguez tests the feasibility of community-based participatory research approaches to engaging Hispanics, African Americans, and the medically underserved in the Buffalo, NY area in biospecimen donation for cancer research.

The economics of biobanking and pharmacogenetics databasing: the case of an adaptive platform on breast cancer.

PubMed

Huttin, Christine C; Liebman, Michael N

2013-01-01

This paper aims to discuss the economics of biobanking. Among the critical issues in evaluating potential ROI for creation of a bio-bank are: scale (e.g. local, national, international), centralized versus virtual/distributed, degree of sample annotation/QC procedures, targeted end-users and uses, types of samples, potential characterization, both of samples and annotations. The paper presents a review on cost models for an economic analysis of biobanking for different steps: data collection (e.g. biospecimens in different types of sites, storage, transport and distribution, information management for the different types of information (e.g. biological information such as cell, gene, and protein)). It also provides additional concepts to process biospecimens from laboratory to clinical practice and will help to identify how changing paradigms in translational medicine affect the economic modeling.

Utility of inverse probability weighting in molecular pathological epidemiology.

PubMed

Liu, Li; Nevo, Daniel; Nishihara, Reiko; Cao, Yin; Song, Mingyang; Twombly, Tyler S; Chan, Andrew T; Giovannucci, Edward L; VanderWeele, Tyler J; Wang, Molin; Ogino, Shuji

2018-04-01

As one of causal inference methodologies, the inverse probability weighting (IPW) method has been utilized to address confounding and account for missing data when subjects with missing data cannot be included in a primary analysis. The transdisciplinary field of molecular pathological epidemiology (MPE) integrates molecular pathological and epidemiological methods, and takes advantages of improved understanding of pathogenesis to generate stronger biological evidence of causality and optimize strategies for precision medicine and prevention. Disease subtyping based on biomarker analysis of biospecimens is essential in MPE research. However, there are nearly always cases that lack subtype information due to the unavailability or insufficiency of biospecimens. To address this missing subtype data issue, we incorporated inverse probability weights into Cox proportional cause-specific hazards regression. The weight was inverse of the probability of biomarker data availability estimated based on a model for biomarker data availability status. The strategy was illustrated in two example studies; each assessed alcohol intake or family history of colorectal cancer in relation to the risk of developing colorectal carcinoma subtypes classified by tumor microsatellite instability (MSI) status, using a prospective cohort study, the Nurses' Health Study. Logistic regression was used to estimate the probability of MSI data availability for each cancer case with covariates of clinical features and family history of colorectal cancer. This application of IPW can reduce selection bias caused by nonrandom variation in biospecimen data availability. The integration of causal inference methods into the MPE approach will likely have substantial potentials to advance the field of epidemiology.

A review of room temperature storage of biospecimen tissue and nucleic acids for anatomic pathology laboratories and biorepositories

PubMed Central

Lou, Jerry J; Mirsadraei, Leili; Sanchez, Desiree E; Wilson, Ryan W; Shabihkhani, Maryam; Lucey, Gregory M; Wei, Bowen; Singer, Elyse J; Mareninov, Sergey; Yong, William H

2014-01-01

Frozen biospecimens are crucial for translational research and contain well preserved nucleic acids and protein. However, the risk for catastrophic freezer failure as well as space, cost, and environmental concerns argue for evaluating long-term room temperature storage alternatives. Formalin-fixed paraffin embedded (FFPE) tissues have great value but their use is limited by cross-linking and fragmentation of nucleic acids, as well as loss of enzymatic activity. Stabilization solutions can now robustly preserve fresh tissue for up to 7 days at room temperature. For longer term storage, commercial vendors of chemical matrices claim real time stability of nucleic acids of over 2 years and their accelerated aging studies to date suggest stability for 12 years for RNA and 60 years for DNA. However, anatomic pathology biorepositories store mostly frozen tissue rather than nucleic acids. Small quantities of tissue can be directly placed on some chemical matrices to stabilize DNA, however RNA and proteins are not preserved. Current lyophilization approaches can preserve histomorphology, DNA, RNA, and proteins though RNA shows moderate degradation after 1–2 years. Formalin free fixatives show improved but varying abilities to preserve nucleic acids and face validation as well as cost barriers in replacing FFPE specimens. The paraffin embedding process can degrade RNA. Development of robust long-term room temperature biospecimen tissue storage technology can potentially reduce costs for the biomedical community in the face of growing targeted therapy needs and decreasing budgets. PMID:24362270

Preanalytical Nonconformity Management Regarding Primary Tube Mixing in Brazil.

PubMed

Lima-Oliveira, Gabriel; Cesare Guidi, Gian; Guimaraes, Andre Valpassos Pacifici; Abol Correa, Jose; Lippi, Giuseppe

2017-01-01

The multifaceted clinical laboratory process is divided in three essential phases: the preanalytical, analytical and postanalytical phase. Problems emerging from the preanalytical phase are responsible for more than 60% of laboratory errors. This report is aimed at highlighting and discussing nonconformity (e.g., nonstandardized procedures) in primary blood tube mixing immediately after blood collection by venipuncture with evacuated tube systems. From January 2015 to December 2015, fifty different laboratory quality managers from Brazil were contacted to request their internal audit reports on nonconformity regarding primary blood tube mixing immediately after blood collection by venipuncture performed using evacuated tube systems. A minority of internal audits (i.e., 4%) concluded that evacuated blood tubes were not accurately mixed after collection, whereas more than half of them reported that evacuated blood tubes were vigorously mixed immediately after collection, thus magnifying the risk of producing spurious hemolysis. Despite the vast ma jority of centers declaring that evacuated blood tubes were mixed gently and carefully, the overall number of inversions was found to be different from that recommended by the manufacturer. Since the turbulence generated by the standard vacuum pressure inside the primary evacuated tubes seems to be sufficient for providing solubilization, mixing and stabilization between additives and blood during venipuncture, avoidance of primary tube mixing probably does not introduce a major bias in tests results and may not be considered a nonconformity during audits for accreditation.

Advancing haemostasis automation--successful implementation of robotic centrifugation and sample processing in a tertiary service hospital.

PubMed

Sédille-Mostafaie, Nazanin; Engler, Hanna; Lutz, Susanne; Korte, Wolfgang

2013-06-01

Laboratories today face increasing pressure to automate operations due to increasing workloads and the need to reduce expenditure. Few studies to date have focussed on the laboratory automation of preanalytical coagulation specimen processing. In the present study, we examined whether a clinical chemistry automation protocol meets the preanalytical requirements for the analyses of coagulation. During the implementation of laboratory automation, we began to operate a pre- and postanalytical automation system. The preanalytical unit processes blood specimens for chemistry, immunology and coagulation by automated specimen processing. As the production of platelet-poor plasma is highly dependent on optimal centrifugation, we examined specimen handling under different centrifugation conditions in order to produce optimal platelet deficient plasma specimens. To this end, manually processed models centrifuged at 1500 g for 5 and 20 min were compared to an automated centrifugation model at 3000 g for 7 min. For analytical assays that are performed frequently enough to be targets for full automation, Passing-Bablok regression analysis showed close agreement between different centrifugation methods, with a correlation coefficient between 0.98 and 0.99 and a bias between -5% and +6%. For seldom performed assays that do not mandate full automation, the Passing-Bablok regression analysis showed acceptable to poor agreement between different centrifugation methods. A full automation solution is suitable and can be recommended for frequent haemostasis testing.

Health behavior change: can genomics improve behavioral adherence?

PubMed

McBride, Colleen M; Bryan, Angela D; Bray, Molly S; Swan, Gary E; Green, Eric D

2012-03-01

The National Human Genome Research Institute recommends pursuing "genomic information to improve behavior change interventions" as part of its strategic vision for genomics. The limited effectiveness of current behavior change strategies may be explained, in part, by their insensitivity to individual variation in adherence responses. The first step in evaluating whether genomics can inform customization of behavioral recommendations is evidence reviews to identify adherence macrophenotypes common across behaviors and individuals that have genetic underpinnings. Conceptual models of how biological, psychological, and environmental factors influence adherence also are needed. Researchers could routinely collect biospecimens and standardized adherence measurements of intervention participants to enable understanding of genetic and environmental influences on adherence, to guide intervention customization and prospective comparative effectiveness studies.

Post-sampling release of free fatty acids - effects of heat stabilization and methods of euthanasia.

PubMed

Jernerén, Fredrik; Söderquist, Marcus; Karlsson, Oskar

2015-01-01

The field of lipid research has made progress and it is now possible to study the lipidome of cells and organelles. A basic requirement of a successful lipid study is adequate pre-analytical sample handling, as some lipids can be unstable and postmortem changes can cause substantial accumulation of free fatty acids (FFAs). The aim of the present study was to investigate the effects of conductive heat stabilization and euthanasia methods on FFA levels in the rat brain and liver using liquid chromatography tandem mass spectrometry. The analysis of brain homogenates clearly demonstrated phospholipase activity and time-dependent post-sampling changes in the lipid pool of snap frozen non-stabilized tissue. There was a significant increase in FFAs already at 2min, which continued over time. Heat stabilization was shown to be an efficient method to reduce phospholipase activity and ex vivo lipolysis. Post-sampling effects due to tissue thawing and sample preparation induced a massive release of FFAs (up to 3700%) from non-stabilized liver and brain tissues compared to heat stabilized tissue. Furthermore, the choice of euthanasia method significantly influenced the levels of FFAs in the brain. The FFAs were decreased by 15-44% in the group of animals euthanized by pentobarbital injection compared with CO2 inhalation or decapitation. Our results highlight the importance of considering euthanasia methods and pre-analytical treatment in lipid analysis, factors which may otherwise interfere with the outcome of the experiments. Copyright © 2014 Elsevier Inc. All rights reserved.

NCI Cohort Consortium

Cancer.gov

The NCI Cohort Consortium is an extramural-intramural partnership formed by the National Cancer Institute to address the need for large-scale collaborations to pool the large quantity of data and biospecimens necessary to conduct a wide range of cancer studies.

Measuring molecular biomarkers in epidemiologic studies: laboratory techniques and biospecimen considerations.

PubMed

Erickson, Heidi S

2012-09-28

The future of personalized medicine depends on the ability to efficiently and rapidly elucidate a reliable set of disease-specific molecular biomarkers. High-throughput molecular biomarker analysis methods have been developed to identify disease risk, diagnostic, prognostic, and therapeutic targets in human clinical samples. Currently, high throughput screening allows us to analyze thousands of markers from one sample or one marker from thousands of samples and will eventually allow us to analyze thousands of markers from thousands of samples. Unfortunately, the inherent nature of current high throughput methodologies, clinical specimens, and cost of analysis is often prohibitive for extensive high throughput biomarker analysis. This review summarizes the current state of high throughput biomarker screening of clinical specimens applicable to genetic epidemiology and longitudinal population-based studies with a focus on considerations related to biospecimens, laboratory techniques, and sample pooling. Copyright © 2012 John Wiley & Sons, Ltd.

A New Paradigm for Biospecimen Banking in the Personalized Medicine Era

PubMed Central

McDonald, Sandra A.; Watson, Mark A.; Rossi, Joan; Becker, Colleen M.; Jaques, David P.; Pfeifer, John D.

2012-01-01

Banking of high-quality, appropriately consented human tissue is crucial for the understanding of disease pathogenesis and translation of such knowledge into improvements in patient care. Traditionally, tissue banking has been thought of as primarily an academic research activity, but tissue and biospecimen banking is increasingly assuming clinical importance, especially with the advent of genetic and proteomic testing approaches that rely on fresh or fresh frozen tissue. These approaches are part of the revolution in personalized medicine. This revolution’s impact on biorepositories—their mission and day-to-day function—will be profound. Direct patient care will require structuring tissue procurement to become a routine part of patient care. Accordingly tissue banking will expand from its traditional research role in large academic medical centers into the everyday practice of surgical pathology. Successful implementation of this model will require consideration of several financial, medicolegal, and administrative issues. PMID:22031304

Broad Consent For Research With Biological Samples: Workshop Conclusions

PubMed Central

Grady, Christine; Eckstein, Lisa; Berkman, Ben; Brock, Dan; Cook-Deegan, Robert; Fullerton, Stephanie M.; Greely, Hank; Hansson, Mats G.; Hull, Sara; Kim, Scott; Lo, Bernie; Pentz, Rebecca; Rodriguez, Laura; Weil, Carol; Wilfond, Benjamin S.; Wendler, David

2016-01-01

Different types of consent are used to obtain human biospecimens for future research. This variation has resulted in confusion regarding what research is permitted, inadvertent constraints on future research, and research proceeding without consent. The NIH Clinical Center’s Department of Bioethics held a workshop to consider the ethical acceptability of addressing these concerns by using broad consent for future research on stored biospecimens. Multiple bioethics scholars, who have written on these issues, discussed the reasons for consent, the range of consent strategies, gaps in our understanding, and concluded with a proposal for broad initial consent coupled with oversight and, when feasible, ongoing provision of information to donors. The manuscript describes areas of agreement as well as areas that need more research and dialogue. Given recent proposed changes to the Common Rule, and new guidance regarding storing and sharing data and samples, this is an important and timely topic. PMID:26305750

Pre-analytic evaluation of volumetric absorptive microsampling and integration in a mass spectrometry-based metabolomics workflow.

PubMed

Volani, Chiara; Caprioli, Giulia; Calderisi, Giovanni; Sigurdsson, Baldur B; Rainer, Johannes; Gentilini, Ivo; Hicks, Andrew A; Pramstaller, Peter P; Weiss, Guenter; Smarason, Sigurdur V; Paglia, Giuseppe

2017-10-01

Volumetric absorptive microsampling (VAMS) is a novel approach that allows single-drop (10 μL) blood collection. Integration of VAMS with mass spectrometry (MS)-based untargeted metabolomics is an attractive solution for both human and animal studies. However, to boost the use of VAMS in metabolomics, key pre-analytical questions need to be addressed. Therefore, in this work, we integrated VAMS in a MS-based untargeted metabolomics workflow and investigated pre-analytical strategies such as sample extraction procedures and metabolome stability at different storage conditions. We first evaluated the best extraction procedure for the polar metabolome and found that the highest number and amount of metabolites were recovered upon extraction with acetonitrile/water (70:30). In contrast, basic conditions (pH 9) resulted in divergent metabolite profiles mainly resulting from the extraction of intracellular metabolites originating from red blood cells. In addition, the prolonged storage of blood samples at room temperature caused significant changes in metabolome composition, but once the VAMS devices were stored at - 80 °C, the metabolome remained stable for up to 6 months. The time used for drying the sample did also affect the metabolome. In fact, some metabolites were rapidly degraded or accumulated in the sample during the first 48 h at room temperature, indicating that a longer drying step will significantly change the concentration in the sample. Graphical abstract Volumetric absorptive microsampling (VAMS) is a novel technology that allows single-drop blood collection and, in combination with mass spectrometry (MS)-based untargeted metabolomics, represents an attractive solution for both human and animal studies. In this work, we integrated VAMS in a MS-based untargeted metabolomics workflow and investigated pre-analytical strategies such as sample extraction procedures and metabolome stability at different storage conditions. The latter revealed that prolonged storage of blood samples at room temperature caused significant changes in metabolome composition, but if VAMS devices were stored at - 80 °C, the metabolome remained stable for up to 6 months.

Pre-Analytical Components of Risk in Four Branches of Clinical Laboratory in Romania--Prospective Study.

PubMed

David, Remona E; Dobreanu, Minodora

2016-01-01

Development of quality measurement principles is a strategic point for each clinical laboratory. Preexamination process is the most critical and the most difficult to be managed. The aim of this study is to identify, quantify, and monitor the nonconformities of the pre-analytical process using quality indicators that can affect the patient's health safety in four different locations of a Romanian private clinical laboratory. The study group consisted of all the analysis requests received by the departments of biochemistry, hematology, and coagulation from January through March 2015. In order to collect the pre-analytical nonconformities, we created a "Risk Budget", using the entries from the "Evidence notebook--non-conform samples" from the above mentioned departments. The laboratory established the quality indicators by means of the risk management technique in order to identify and control the sources of errors, FMEA (Failure Modes and Effects Analyses), which had been implemented and monitored for its purposes and special needs. For the assessment of the control level over the processes, the results were transformed on the Six Sigma scale, using the Westgard calculation method and being obtained in this way the frequency with which an error may occur. (https://www.westgard. com/six-sigma-calculators.htm). The obtained results prove that the quantification and monitoring of the indicators can be a control instrument for the pre-analytic activities. The calculation of the Six Sigma value adds extra information to the study because it allows the detection of the processes which need improvement (Sigma value higher than 4 represents a well controlled process). The highest rates were observed for the hemolyzed and the lipemic samples, in the department of biochemistry and hemolyzed, insufficient sample volume, or clotted samples for the department of hematology and coagulation. Significant statistical differences between laboratories participating in the study have been recorded for these indicators. The elaborated study between the four branches of a Romanian private clinical laboratory was a challenge, and it helped in choosing strategic decisions regarding the improvement of the patient's health safety in the institution, corresponding to the accreditation requirements in accordance with ISO 15189:2013.

Biobanking 3.0: evidence based and customer focused biobanking.

PubMed

Simeon-Dubach, Daniel; Watson, Peter

2014-03-01

Biobanking is a new and very dynamic field. To achieve long term financial sustainability of biobank infrastructures we propose that a new focus is needed on activities, products and services provided by the biobank that relate to the external stakeholder: biobanking 3.0. Earlier stages of biobanking are biobanking 1.0 (primary focus on the number of biospecimens and data) and biobanking 2.0 (primary focus on the quality of biospecimens and data). Both stages 1.0 and 2.0 are predominantly product oriented areas and have required a mostly internal focus on operational development within the biobank itself. In this paper we will introduce our concept of biobanking 3.0 which capitalizes on the earlier stages but dictates a shift in focus to enhancing the value and impact for the three major sets of external stakeholders (people/patients, funders, and research customers) and creating a path to balanced and planned investment in biobank infrastructure and the sustainability of biobanking. Biobanking 3.0 will improve real understanding as well as perceptions of value across different stakeholders. Patients and donors will appreciate seeing how their biospecimens and data are effectively used for research. Funders will value the ability to plan efficient targeting of funding and to monitor the impact of their support. Researchers will capitalize on the ability to translate their ideas into effective knowledge. Ultimately adoption of biobanking 3.0 will impact on the sustainability in the three main dimensions relevant to biobanking: social sustainability (acceptability), operational sustainability (efficiency), and financial sustainability (accomplishment). Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

The Greater Cincinnati Pediatric Clinic Repository: A Novel Framework for Childhood Asthma and Allergy Research

PubMed Central

Butsch Kovacic, Melinda; Biagini Myers, Jocelyn M.; Lindsey, Mark; Patterson, Tia; Sauter, Sharon; Ericksen, Mark B.; Ryan, Patrick; Assa'ad, Amal; Lierl, Michelle; Fischer, Thomas; Kercsmar, Carolyn; McDowell, Karen; Lucky, Anne W.; Sheth, Anita P.; Hershey, Andrew D.; Ruddy, Richard M.; Rothenberg, Marc E.

2012-01-01

Background Allergic disorders, including asthma, allergic rhinitis, atopic dermatitis, eosinophilic esophagitis, and food allergy, are a major global health burden. The study and management of allergic disorders is complicated by the considerable heterogeneity in both the presentation and natural history of these disorders. Biorepositories serve as an excellent source of data and biospecimens for delineating subphenotypes of allergic disorders, but such resources are lacking. Methods In order to define subphenotypes of allergic disease accurately, we established an infrastructure to link and efficiently utilize clinical and epidemiologic data with biospecimens into a single biorepository called the Greater Cincinnati Pediatric Clinic Repository (GCPCR). Children with allergic disorders as well as healthy controls are followed longitudinally at hospital clinic, emergency department, and inpatient visits. Subjects' asthma, allergy, and skin symptoms; past medical, family, social, diet, and environmental histories; physical activity; medication adherence; perceived quality of life; and demographics are ascertained. DNA is collected from all participants, and other biospecimens such as blood, hair, and nasal epithelial cells are collected on a subset. Results To date, the GCPCR has 6,317 predominantly Caucasian and African American participants, and 93% have banked DNA. This large sample size supports adequately powered genetic, epidemiologic, environmental, and health disparities studies of childhood allergic diseases. Conclusions The GCPCR is a unique biorepository that is continuously evaluated and refined to achieve and maintain rigorous clinical phenotype and biological data. Development of similar disease-specific repositories using common data elements is necessary to enable studies across multiple populations of comprehensively phenotyped patients. PMID:22768387

Biomarker of Long-Chain n-3 Fatty Acid Intake and Breast Cancer: Accumulative Evidence from an Updated Meta-Analysis of Epidemiological Studies.

PubMed

Yang, Bo; Ren, Xiao L; Wang, Zhi Y; Wang, Liang; Zhao, Feng; Guo, Xiao J; Li, Duo

2018-06-14

We aimed to summarize the up-to-date epidemiology evidence on biomarkers of long-chain (LC) n-3 fatty acid (FA) intake in relation to breast cancer (BC). Epidemiology studies determining FA levels in biospecimen (circulating blood or adipose tissue (AT)) were identified from PubMed, EMBASE, and Cochrane Library databases until March 2018. Multivariate-adjusted risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effect model. Difference in biospecimen proportions of LC n-3 FA between BC cases and non-cases were analyzed as a standardized mean difference (SMD). Thirteen cohort and eleven case-control studies were eligible for the present meta-analysis. The estimated SMD was -0.14 (95% CI: -0.27, -0.11) for LC n-3 FA and -0.27 (95% CI: -0.42, -0.11) for LC n-3/n-6 FA ratio. When comparing the top tertiles with the bottom baseline levels, circulating LC n-3 FA was significantly associated with a lower risk of BC (RR: 0.84, 95% CI: 0.74, 0.96), but not AT (RR: 1.02, 95% CI: 0.70, 1.48). Significant inverse dose-response associations were observed for each 1% increment of circulating 20:5n-3 and 22:6n-3. This meta-analysis highlights that circulating LC n-3 FA as a biomarker of intake may be an independent predictive factor for BC, especially 20:5n-3 and 22:6n-3.

The LEGACY Girls Study: Growth and Development in the Context of Breast Cancer Family History.

PubMed

John, Esther M; Terry, Mary Beth; Keegan, Theresa H M; Bradbury, Angela R; Knight, Julia A; Chung, Wendy K; Frost, Caren J; Lilge, Lothar; Patrick-Miller, Linda; Schwartz, Lisa A; Whittemore, Alice S; Buys, Saundra S; Daly, Mary B; Andrulis, Irene L

2016-05-01

Although the timing of pubertal milestones has been associated with breast cancer risk, few studies of girls' development include girls at increased breast cancer risk due to their family history. The Lessons in Epidemiology and Genetics of Adult Cancer from Youth (LEGACY) Girls Study was initiated in 2011 in the USA and Canada to assess the relation between early life exposures and intermediate markers of breast cancer risk (e.g., pubertal development, breast tissue characteristics) and to investigate psychosocial well being and health behaviors in the context of family history. We describe the methods used to establish and follow a cohort of 1,040 girls ages 6-13 years at baseline, half with a breast cancer family history, and the collection of questionnaire data (family history, early life exposures, growth and development, psychosocial and behavioral), anthropometry, biospecimens, and breast tissue characteristics using optical spectroscopy. During this initial 5-year phase of the study, follow-up visits are conducted every 6 months for repeated data and biospecimen collection. Participation in baseline components was high (98% for urine, 97.5% for blood or saliva, and 98% for anthropometry). At enrollment, 77% of girls were premenarcheal and 49% were at breast Tanner stage T1. This study design allows thorough examination of events affecting girls' growth and development and how they differ across the spectrum of breast cancer risk. A better understanding of early life breast cancer risk factors will be essential to enhance prevention across the lifespan for those with and without a family history of the disease.

Religiousness, Spirituality, and Salivary Cortisol in Breast Cancer Survivorship: A Pilot Study.

PubMed

Hulett, Jennifer M; Armer, Jane M; Leary, Emily; Stewart, Bob R; McDaniel, Roxanne; Smith, Kandis; Millspaugh, Rami; Millspaugh, Joshua

Psychoneuroimmunological theory suggests a physiological relationship exists between stress, psychosocial-behavioral factors, and neuroendocrine-immune outcomes; however, evidence has been limited. The primary aim of this pilot study was to determine feasibility and acceptability of a salivary cortisol self-collection protocol with a mail-back option for breast cancer survivors. A secondary aim was to examine relationships between religiousness/spirituality (R/S), perceptions of health, and diurnal salivary cortisol (DSC) as a proxy measure for neuroendocrine activity. This was an observational, cross-sectional study. Participants completed measures of R/S, perceptions of health, demographics, and DSC. The sample was composed of female breast cancer survivors (n = 41). Self-collection of DSC using a mail-back option was feasible; validity of mailed salivary cortisol biospecimens was established. Positive spiritual beliefs were the only R/S variable associated with the peak cortisol awakening response (rs = 0.34, P = .03). Poorer physical health was inversely associated with positive spiritual experiences and private religious practices. Poorer mental health was inversely associated with spiritual coping and negative spiritual experiences. Feasibility, validity, and acceptability of self-collected SDC biospecimens with an optional mail-back protocol (at moderate temperatures) were demonstrated. Positive spiritual beliefs were associated with neuroendocrine-mediated peak cortisol awakening response activity; however, additional research is recommended. Objective measures of DSC sampling that include enough collection time points to assess DSC parameters would increase the rigor of future DSC measurement. Breast cancer survivors may benefit from nursing care that includes spiritual assessment and therapeutic conversations that support positive spiritual beliefs.

The LEGACY Girls Study: Growth and development in the context of breast cancer family history

PubMed Central

John, Esther M.; Terry, Mary Beth; Keegan, Theresa H.M.; Bradbury, Angela R.; Knight, Julia A.; Chung, Wendy K.; Frost, Caren J.; Lilge, Lothar; Patrick-Miller, Linda; Schwartz, Lisa A.; Whittemore, Alice S.; Buys, Saundra S.; Daly, Mary B.; Andrulis, Irene L.

2017-01-01

Background Although the timing of pubertal milestones has been associated with breast cancer risk, few studies of girls’ development include girls at increased breast cancer risk due to their family history. Methods The LEGACY (Lessons in Epidemiology and Genetics of Adult Cancer from Youth) Girls Study was initiated in 2011 in the USA and Canada to assess the relation between early-life exposures and intermediate markers of breast cancer risk (e.g., pubertal development, breast tissue characteristics) and to investigate psychosocial well-being and health behaviors in the context of family history. We describe the methods used to establish and follow a cohort of 1,040 girls ages 6–13 years at baseline, half with a breast cancer family history, and the collection of questionnaire data (family history, early-life exposures, growth and development, psychosocial and behavioral), anthropometry, biospecimens, and breast tissue characteristics using optical spectroscopy. Results During this initial 5-year phase of the study, follow-up visits are conducted every six months for repeated data and biospecimen collection. Participation in baseline components was high (98% for urine, 97.5% for blood or saliva, and 98% for anthropometry). At enrollment, 77% of girls were pre-menarcheal and 49% were at breast Tanner stage T1. Conclusions This study design allows thorough examination of events affecting girls’ growth and development and how they differ across the spectrum of breast cancer risk. A better understanding of early-life breast cancer risk factors will be essential to enhance prevention across the lifespan for those with and without a family history of the disease. PMID:26829160

[Automation and organization of technological process of urinalysis].

PubMed

Kolenkin, S M; Kishkun, A A; Kol'chenko, O L

2000-12-01

Results of introduction into practice of a working model of industrial technology of laboratory studies and KONE Specific Supra and Miditron M devices are shown as exemplified by clinical analysis of the urine. This technology helps standardize all stages and operations, improves the efficiency of quality control of laboratory studies, rationally organizes the work at all stages of the process, creates a system for permanent improvement of the efficiency of investigations at the preanalytical, analytical, and postanalytical stages of technological process of laboratory studies. As a result of introduction of this technology into laboratory practice, violations of quality criteria of clinical urinalysis decreased from 15 to 8% at the preanalytical stage and from 6 to 3% at the analytical stage. Automation of the analysis decreased the need in reagents 3-fold and improved the productivity at the analytical stage 4-fold.

Pre-analytical method for NMR-based grape metabolic fingerprinting and chemometrics.

PubMed

Ali, Kashif; Maltese, Federica; Fortes, Ana Margarida; Pais, Maria Salomé; Verpoorte, Robert; Choi, Young Hae

2011-10-10

Although metabolomics aims at profiling all the metabolites in organisms, data quality is quite dependent on the pre-analytical methods employed. In order to evaluate current methods, different pre-analytical methods were compared and used for the metabolic profiling of grapevine as a model plant. Five grape cultivars from Portugal in combination with chemometrics were analyzed in this study. A common extraction method with deuterated water and methanol was found effective in the case of amino acids, organic acids, and sugars. For secondary metabolites like phenolics, solid phase extraction with C-18 cartridges showed good results. Principal component analysis, in combination with NMR spectroscopy, was applied and showed clear distinction among the cultivars. Primary metabolites such as choline, sucrose, and leucine were found discriminating for 'Alvarinho', while elevated levels of alanine, valine, and acetate were found in 'Arinto' (white varieties). Among the red cultivars, higher signals for citrate and GABA in 'Touriga Nacional', succinate and fumarate in 'Aragonês', and malate, ascorbate, fructose and glucose in 'Trincadeira', were observed. Based on the phenolic profile, 'Arinto' was found with higher levels of phenolics as compared to 'Alvarinho'. 'Trincadeira' showed lowest phenolics content while higher levels of flavonoids and phenylpropanoids were found in 'Aragonês' and 'Touriga Nacional', respectively. It is shown that the metabolite composition of the extract is highly affected by the extraction procedure and this consideration has to be taken in account for metabolomics studies. Copyright © 2011 Elsevier B.V. All rights reserved.

Preanalytical requirements for flow cytometric evaluation of platelet activation: choice of anticoagulant.

PubMed

Mody, M; Lazarus, A H; Semple, J W; Freedman, J

1999-06-01

Accurate assessment of in vivo or in vitro platelet activation requires optimal preanalytical conditions to prevent artefactual in vitro activation of the platelets. The choice of anticoagulant is one of the critical preanalytical conditions as anticoagulants exert different effects on the activation of platelets ex vivo. We tested the effectiveness of Diatube-H (also known as CTAD; sodium citrate, theophylline, adenosine and dipyridamole) and citrate vacutainer tubes in preventing artefactual activation of platelets and preserving functional reserve. Platelet surface expression of the CD62P (reflecting alpha granule release), CD63 (reflecting lysosomal release) and modulation of normal platelet membrane glycoproteins CD41a and CD42b, were measured in whole blood and in isolated platelets immediately after collection and at 6, 24 and 48 h after venipuncture. Samples taken into Diatube-H showed less spontaneous platelet activation than did those taken into citrate. To measure in vitro platelet functional reserve, thrombin was added as agonist to blood stored for varying periods up to 48 h. Although Diatube-H suppressed in vitro platelet activation for up to 4 h, in samples kept for 6-24 h before thrombin addition, the inhibitory effect was lost and platelets responded fully to agonist activation. Hence, Diatube-H preserved platelets and allowed for measurement of in vivo platelet activation as well as thrombin-induced in vitro platelet activation after 6-24 h, in both whole blood and isolated platelets.

Contamination of dried blood spots - an underestimated risk in newborn screening.

PubMed

Winter, Theresa; Lange, Anja; Hannemann, Anke; Nauck, Matthias; Müller, Cornelia

2018-01-26

Newborn screening (NBS) is an established screening procedure in many countries worldwide, aiming at the early detection of inborn errors of metabolism. For decades, dried blood spots have been the standard specimen for NBS. The procedure of blood collection is well described and standardized and includes many critical pre-analytical steps. We examined the impact of contamination of some anticipated common substances on NBS results obtained from dry spot samples. This possible pre-analytical source of uncertainty has been poorly examined in the past. Capillary blood was obtained from 15 adult volunteers and applied to 10 screening filter papers per volunteer. Nine filter papers were contaminated without visible trace. The contaminants were baby diaper rash cream, baby wet wipes, disinfectant, liquid infant formula, liquid infant formula hypoallergenic (HA), ultrasonic gel, breast milk, feces, and urine. The differences between control and contaminated samples were evaluated for 45 NBS quantities. We estimated if the contaminations might lead to false-positive NBS results. Eight of nine investigated contaminants significantly altered NBS analyte concentrations and potentially caused false-positive screening outcomes. A contamination with feces was most influential, affecting 24 of 45 tested analytes followed by liquid infant formula (HA) and urine, affecting 19 and 13 of 45 analytes, respectively. A contamination of filter paper samples can have a substantial effect on the NBS results. Our results underline the importance of good pre-analytical training to make the staff aware of the threat and ensure reliable screening results.

Steps Towards Precision Medicine: Utilizing FFPE Specimens - TCGA

Cancer.gov

Roy W. Tarnuzzer, Ph.D., the Biospecimen Core Resource Program Manager at the TCGA Program Office, provides an overview of the Formalin-fixed Paraffin Pilot Project, an initiative to investigate best practices for use of FFPE specimens in genomic studies.

Health Behavior Change: Can Genomics Improve Behavioral Adherence?

PubMed Central

Bryan, Angela D.; Bray, Molly S.; Swan, Gary E.; Green, Eric D.

2012-01-01

The National Human Genome Research Institute recommends pursuing “genomic information to improve behavior change interventions” as part of its strategic vision for genomics. The limited effectiveness of current behavior change strategies may be explained, in part, by their insensitivity to individual variation in adherence responses. The first step in evaluating whether genomics can inform customization of behavioral recommendations is evidence reviews to identify adherence macrophenotypes common across behaviors and individuals that have genetic underpinnings. Conceptual models of how biological, psychological, and environmental factors influence adherence also are needed. Researchers could routinely collect biospecimens and standardized adherence measurements of intervention participants to enable understanding of genetic and environmental influences on adherence, to guide intervention customization and prospective comparative effectiveness studies. PMID:22390502

75 FR 34146 - Proposed Collection; Comment Request Resource for the Collection and Evaluation of Human Tissues...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... summaries of proposed projects to be submitted to the Office of Management and Budget (OMB) for review and... obtain the personal histories to compare to the life styles and exposures and the biospecimens will serve...

Participation in Pediatric Oncology Research Protocols: Racial/ethnic, Language and Age-based Disparities

PubMed Central

Aristizabal, Paula; Singer, Jenelle; Cooper, Renee; Wells, Kristen J.; Nodora, Jesse; Milburn, Mehrzad; Gahagan, Sheila; Schiff, Deborah E.; Martinez, Maria Elena

2015-01-01

Background Survival rates in pediatric oncology have improved dramatically, in part due to high patient participation in clinical trials. Although racial/ethnic inequalities in clinical trial participation have been reported in adults, pediatric data and studies comparing participation rates by socio-demographic characteristics are scarce. The goal of this study was to assess differences in research protocol participation for childhood cancer by age, sex, race/ethnicity, parental language, cancer type and insurance status. Procedure Data on enrollment in any protocol, biospecimen, or therapeutic protocols were collected and analyzed for newly diagnosed pediatric patients with cancer from 2008–2012 at Rady Children’s Hospital. Results Among the 353 patients included in the analysis, 304 (86.1%) were enrolled in any protocol. Enrollment in biospecimen and therapeutic protocols was 84.2% (261/310) and 81.1% (206/254), respectively. Logistic regression analyses revealed significant enrollment underrepresentation in any protocol for Hispanics compared to Non-Hispanic whites (81% vs. 91%; Odds Ratio [OR], 0.43; 95% Confidence Interval [CI], 0.21–0.90; p=0.021) and among children of Spanish-speaking vs. English-speaking parents (78% vs. 89%; OR, 0.45; 95%CI, 0.23–0.87; p=0.016). Compared to patients aged 0–4 years, significant underrepresentation was also found among patients 15–21 years old (92% vs.72%; OR, 0.21; 95% CI, 0.09–0.48; p<0.001). Similar trends were observed when analyzing enrollment in biospecimen and therapeutic protocols separately. Conclusions There was significant underrepresentation in protocol participation for Hispanics, children of Spanish-speaking parents, and patients ages 15–21. Research is urgently needed to understand barriers to research participation among these groups underrepresented in pediatric oncology clinical trials. PMID:25755225

An empirical assessment of the short-term impacts of a reading of Deborah Zoe Laufer's drama Informed Consent on attitudes and intentions to participate in genetic research.

PubMed

Rothwell, Erin; Botkin, Jeffrey R; Cheek-O'Donnell, Sydney; Wong, Bob; Case, Gretchen A; Johnson, Erin; Matheson, Trent; Wilson, Alena; Robinson, Nicole R; Rawlings, Jared; Horejsi, Brooke; Lopez, Ana Maria; Byington, Carrie L

2018-01-01

This study assessed the short-term impact of the play "Informed Consent" by Deborah Zoe Laufer (a fictionalized look at the controversy over specimens collected from the Havasupai Tribe for diabetes research in 1989) on perceptions of trust, willingness to donate biospecimens, and attitudes toward harm and privacy among the medical and undergraduate students, faculty, and the public in the Intermountain West. Surveys were administered before and after a staged reading of the play by professional actors. Survey items included the short form Trust in Medical Researchers, and single-item questions about group identity, ethics of genetic testing in children, and willingness to donate biospecimens. In addition, respondents were given the option to answer open-ended questions through e-mail. Out of the 481 who attended the play, 421 completed both the pre and post surveys, and 166 participants completed open-ended questions online approximately 1 week after the play. Across all participants, there were significant declines for trust in medical researchers and for the survey item "is it ethical for investigators to test children for adult onset diseases" (p < .001 for both) following the play. There was a significant increase in agreement to improve group identity protections (p < .001) and there were no differences on willingness to donate biospecimens to research (p = .777). Qualitative data provided extensive contextual data supporting these perspectives. This is one of the first studies to document short-term impacts of a theatrical performance on both attitudes and behavioral intentions toward research ethics and clinical research participation. Future research should continue to explore the impact of theatrical performances among public and investigators on the ethical issues and complexities in clinical research.

Preanalytic Factors Associated With Hemolysis in Emergency Department Blood Samples.

PubMed

Phelan, Michael P; Reineks, Edmunds Z; Schold, Jesse D; Hustey, Frederic M; Chamberlin, Janelle; Procop, Gary W

2018-02-01

- Hemolysis of emergency department blood samples is a common occurrence and has a negative impact on health care delivery. - To determine the effect of preanalytic factors (straight stick, intravenous [IV] line, needle gauge, location of blood draw, syringe versus vacuum tube use, tourniquet time) on hemolysis in emergency department blood samples. - A single 65 000-visit emergency department's electronic health record was queried for emergency department potassium results and blood draw technique for all samples obtained in calendar year 2014, resulting in 54 531 potassium results. Hemolyzed potassium was measured by hemolysis index. Comparisons of hemolysis by sampling technique were conducted by χ 2 tests. - Overall hemolysis was 10.0% (5439 of 54 531). Hemolysis among samples obtained from straight stick was significantly less than among those obtained with IV line (5.4% [33 of 615] versus 10.2% [4821 of 47 266], P < .001). For IV-placed blood draws, antecubital location had a statistically significant lower overall hemolysis compared with other locations: 7.4% (2117 of 28 786) versus 14.6% (2622 of 17 960) ( P < .001). For blood drawn with a syringe compared with vacuum, hemolysis was 13.0% (92 of 705) and 11.0% (1820 of 16 590), respectively ( P = .09, not significant). For large-gauge IV blood draws versus smaller-gauge IV lines, a lower hemolysis was also observed (9.3% [3882 of 41 571] versus 16.7% [939 of 5633]) ( P < .001). For IV-drawn blood with tourniquet time less than 60 seconds, hemolysis was 10.3% (1362 of 13 162) versus 13.9% for more than 60 seconds (532 of 3832), P < .001. - This study confirmed previous findings that straight stick and antecubital location are significantly associated with reduced hemolysis and indicated that shorter tourniquet time and larger gauge for IV draws were significantly associated with lower hemolysis.

[Biochemical markers of bone remodeling: pre-analytical variations and guidelines for their use. SFBC (Société Française de Biologie Clinique) Work Group. Biochemical markers of bone remodeling].

PubMed

Garnero, P; Bianchi, F; Carlier, M C; Genty, V; Jacob, N; Kamel, S; Kindermans, C; Plouvier, E; Pressac, M; Souberbielle, J C

2000-01-01

Biochemical markers of bone turnover have been developed over the past 20 years that are more specific for bone tissue than conventional ones such as total alkaline phosphatase and urinary hydroxyproline. They have been widely used in clinical research and in clinical trials of new therapies as secondary end points of treatment efficacy. Most of the interest has been devoted to their use in postmenopausal osteoporosis, a condition characterized by subtle modifications of bone metabolism that cannot be detected readily by conventional markers of bone turnover. Although several recent studies have suggested that biochemical markers may be used for the management of the individual patient in routine clinical practice, this has not been clearly defined and is a matter of debate. Because of the crucial importance to clarify this issue, the Société Francaise de Biologie Clinique prompted an expert committee to summarize the available data and to make recommendations. The following paper includes a review on the biochemical and analytical aspects of the markers of bone formation and resorption and on the sources of variability such as sex, age, menstrual cycle, pregnancy and lactation, physical activity, seasonal variation and effects of diseases and treatments. We will also describe the effects of pre-analytical factors on the measurements of the different markers. Finally based on that review, we will make practical recommendations for the use of these markers in order to minimize the variability of the measurements and improve the clinical interpretation of the data.

Preanalytical blood sample workup for cell-free DNA analysis using Droplet Digital PCR for future molecular cancer diagnostics.

PubMed

van Ginkel, Joost H; van den Broek, Daan A; van Kuik, Joyce; Linders, Dorothé; de Weger, Roel; Willems, Stefan M; Huibers, Manon M H

2017-10-01

In current molecular cancer diagnostics, using blood samples of cancer patients for the detection of genetic alterations in plasma (cell-free) circulating tumor DNA (ctDNA) is an emerging practice. Since ctDNA levels in blood are low, highly sensitive Droplet Digital PCR (ddPCR) can be used for detecting rare mutational targets. In order to perform ddPCR on blood samples, a standardized procedure for processing and analyzing blood samples is necessary to facilitate implementation into clinical practice. Therefore, we assessed the technical sample workup procedure for ddPCR on blood plasma samples. Blood samples from healthy individuals, as well as lung cancer patients were analyzed. We compared different methods and protocols for sample collection, storage, centrifugation, isolation, and quantification. Cell-free DNA (cfDNA) concentrations of several wild-type targets and BRAF and EGFR-mutant ctDNA concentrations quantified by ddPCR were primary outcome measurements. Highest cfDNA concentrations were measured in blood collected in serum tubes. No significant differences in cfDNA concentrations were detected between various time points of up to 24 h until centrifugation. Highest cfDNA concentrations were detected after DNA isolation with the Quick cfDNA Serum & Plasma Kit, while plasma isolation using the QIAamp Circulating Nucleic Acid Kit yielded the most consistent results. DdPCR results on cfDNA are highly dependent on multiple factors during preanalytical sample workup, which need to be addressed during the development of this diagnostic tool for cancer diagnostics in the future. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

President Signs STAR Act for Kids' Cancers.

PubMed

2018-06-07

On June 5, President Donald Trump signed the Childhood Cancer Survivorship, Treatment, Access and Research Act, which aims to support pediatric cancer research by expanding the collection of patient biospecimens and records, improving surveillance, and investigating pediatric survivorship. ©2018 American Association for Cancer Research.

Translating Metabolomics to Cardiovascular Biomarkers

PubMed Central

Senn, Todd; Hazen, Stanley L.; Tang, W. H. Wilson

2012-01-01

Metabolomics is the systematic study of the unique chemical fingerprints of small-molecules, or metabolite profiles, that are related to a variety of cellular metabolic processes in a cell, organ, or organism. While mRNA gene expression data and proteomic analyses do not tell the whole story of what might be happening in a cell, metabolic profiling provides direct and indirect physiologic insights that can potentially be detectable in a wide range of biospecimens. Although not specific to cardiac conditions, translating metabolomics to cardiovascular biomarkers has followed the traditional path of biomarker discovery from identification and confirmation to clinical validation and bedside testing. With technological advances in metabolomic tools (such as nuclear magnetic resonance spectroscopy and mass spectrometry) and more sophisticated bioinformatics and analytical techniques, the ability to measure low-molecular-weight metabolites in biospecimens provides a unique insight into established and novel metabolic pathways. Systemic metabolomics may provide physiologic understanding of cardiovascular disease states beyond traditional profiling, and may involve descriptions of metabolic responses of an individual or population to therapeutic interventions or environmental exposures. PMID:22824112

Biospecimen repositories and cytopathology.

PubMed

Krishnamurthy, Savitri

2015-03-01

Biospecimen repositories are important for the advancement of biomedical research. Literature on the potential for biobanking of fine-needle aspiration, gynecologic, and nongynecologic cytology specimens is very limited. The potential for biobanking of these specimens as valuable additional resources to surgically excised tissues appears to be excellent. The cervicovaginal specimens that can be used for biobanking include Papanicolaou-stained monolayer preparations and residual material from liquid-based cytology preparations. Different types of specimen preparations of fine-needle aspiration and nongynecologic specimens, including Papanicolaou-stained and Diff-Quik-stained smears, cell blocks. and dedicated passes/residual material from fine-needle aspiration stored frozen in a variety of solutions, can be used for biobanking. Because of several gaps in knowledge regarding the standard of operative procedures for the procurement, storage, and quality assessment of cytology specimens, further studies as well as national conferences and workshops are needed not only to create awareness but also to facilitate the use of cytopathology specimens for biobanking. © 2014 American Cancer Society.

Wetlab-2 - Quantitative PCR Tools for Spaceflight Studies of Gene Expression Aboard the International Space Station

NASA Technical Reports Server (NTRS)

Schonfeld, Julie E.

2015-01-01

Wetlab-2 is a research platform for conducting real-time quantitative gene expression analysis aboard the International Space Station. The system enables spaceflight genomic studies involving a wide variety of biospecimen types in the unique microgravity environment of space. Currently, gene expression analyses of space flown biospecimens must be conducted post flight after living cultures or frozen or chemically fixed samples are returned to Earth from the space station. Post-flight analysis is limited for several reasons. First, changes in gene expression can be transient, changing over a timescale of minutes. The delay between sampling on Earth can range from days to months, and RNA may degrade during this period of time, even in fixed or frozen samples. Second, living organisms that return to Earth may quickly re-adapt to terrestrial conditions. Third, forces exerted on samples during reentry and return to Earth may affect results. Lastly, follow up experiments designed in response to post-flight results must wait for a new flight opportunity to be tested.

Spiking of serum specimens with exogenous reporter peptides for mass spectrometry based protease profiling as diagnostic tool.

PubMed

Findeisen, Peter; Peccerella, Teresa; Post, Stefan; Wenz, Frederik; Neumaier, Michael

2008-04-01

Serum is a difficult matrix for the identification of biomarkers by mass spectrometry (MS). This is due to high-abundance proteins and their complex processing by a multitude of endogenous proteases making rigorous standardisation difficult. Here, we have investigated the use of defined exogenous reporter peptides as substrates for disease-specific proteases with respect to improved standardisation and disease classification accuracy. A recombinant N-terminal fragment of the Adenomatous Polyposis Coli (APC) protein was digested with trypsin to yield a peptide mixture for subsequent Reporter Peptide Spiking (RPS) of serum. Different preanalytical handling of serum samples was simulated by storage of serum samples for up to 6 h at ambient temperature, followed by RPS, further incubation under standardised conditions and testing for stability of protease-generated MS profiles. To demonstrate the superior classification accuracy achieved by RPS, a pilot profiling experiment was performed using serum specimens from pancreatic cancer patients (n = 50) and healthy controls (n = 50). After RPS six different peak categories could be defined, two of which (categories C and D) are modulated by endogenous proteases. These latter are relevant for improved classification accuracy as shown by enhanced disease-specific classification from 78% to 87% in unspiked and spiked samples, respectively. Peaks of these categories presented with unchanged signal intensities regardless of preanalytical conditions. The use of RPS generally improved the signal intensities of protease-generated peptide peaks. RPS circumvents preanalytical variabilities and improves classification accuracies. Our approach will be helpful to introduce MS-based proteomic profiling into routine laboratory testing.

A Six Sigma Trial For Reduction of Error Rates in Pathology Laboratory.

PubMed

Tosuner, Zeynep; Gücin, Zühal; Kiran, Tuğçe; Büyükpinarbaşili, Nur; Turna, Seval; Taşkiran, Olcay; Arici, Dilek Sema

2016-01-01

A major target of quality assurance is the minimization of error rates in order to enhance patient safety. Six Sigma is a method targeting zero error (3.4 errors per million events) used in industry. The five main principles of Six Sigma are defining, measuring, analysis, improvement and control. Using this methodology, the causes of errors can be examined and process improvement strategies can be identified. The aim of our study was to evaluate the utility of Six Sigma methodology in error reduction in our pathology laboratory. The errors encountered between April 2014 and April 2015 were recorded by the pathology personnel. Error follow-up forms were examined by the quality control supervisor, administrative supervisor and the head of the department. Using Six Sigma methodology, the rate of errors was measured monthly and the distribution of errors at the preanalytic, analytic and postanalytical phases was analysed. Improvement strategies were reclaimed in the monthly intradepartmental meetings and the control of the units with high error rates was provided. Fifty-six (52.4%) of 107 recorded errors in total were at the pre-analytic phase. Forty-five errors (42%) were recorded as analytical and 6 errors (5.6%) as post-analytical. Two of the 45 errors were major irrevocable errors. The error rate was 6.8 per million in the first half of the year and 1.3 per million in the second half, decreasing by 79.77%. The Six Sigma trial in our pathology laboratory provided the reduction of the error rates mainly in the pre-analytic and analytic phases.

Assessment of bedside transfusion practices at a tertiary care center: A step closer to controlling the chaos

PubMed Central

Khetan, Dheeraj; Katharia, Rahul; Pandey, Hem Chandra; Chaudhary, Rajendra; Harsvardhan, Rajesh; Pandey, Hemchandra; Sonkar, Atul

2018-01-01

BACKGROUND: Blood transfusion chain can be divided into three phases: preanalytical (patient bedside), analytical (steps done at transfusion services), and postanalytical (bedside). Majority (~70%) of events due to blood transfusion have been attributed to errors in bedside blood administration practices. Survey of bedside transfusion practices (pre-analytical and post analytical phase) was done to assess awareness and compliance to guidelines regarding requisition and administration of blood components. MATERIALS AND METHODS: Interview-based questionnaire of ward staff and observational survey of actual transfusion of blood components in total 26 wards of the institute was carried out during November–December 2013. All the collected data were coded (to maintain confidentiality) and analyzed using SPSS (v 20). For analysis, wards were divided into three categories: medical, surgical, and others (including all intensive care units). RESULTS: A total of 104 (33 resident doctors and 71 nursing) staff members were interviewed and observational survey could be conducted in 25 wards during the study period. In the preanalytical phase, major issues were as follows: lack of awareness for institute guidelines (80.6% not aware), improper sampling practices (67.3%), and prescription related (56.7%). In the postanalytical phase, major issues were found to be lack of consent for blood transfusion (72%), improper warming of blood component (~80%), and problems in storage and discarding of blood units. CONCLUSION: There is need to create awareness about policies and guidelines of bed side transfusion among the ward staff. Regular audits are necessary for compliance to guidelines among clinical staff. PMID:29563672

Looking for new biomarkers of skin wound vitality with a cytokine-based multiplex assay: preliminary study.

PubMed

Peyron, Pierre-Antoine; Baccino, Éric; Nagot, Nicolas; Lehmann, Sylvain; Delaby, Constance

2017-02-01

Determination of skin wound vitality is an important issue in forensic practice. No reliable biomarker currently exists. Quantification of inflammatory cytokines in injured skin with MSD ® technology is an innovative and promising approach. This preliminary study aims to develop a protocol for the preparation and the analysis of skin samples. Samples from ante mortem wounds, post mortem wounds, and intact skin ("control samples") were taken from corpses at the autopsy. After an optimization of the pre-analytical protocol had been performed in terms of skin homogeneisation and proteic extraction, the concentration of TNF-α was measured in each sample with the MSD ® approach. Then five other cytokines of interest (IL-1β, IL-6, IL-10, IL-12p70 and IFN-γ) were simultaneously quantified with a MSD ® multiplex assay. The optimal pre-analytical conditions consist in a proteic extraction from a 6 mm diameter skin sample, in a PBS buffer with triton 0,05%. Our results show the linearity and the reproductibility of the TNF-α quantification with MSD ® , and an inter- and intra-individual variability of the concentrations of proteins. The MSD ® multiplex assay is likely to detect differential skin concentrations for each cytokine of interest. This preliminary study was used to develop and optimize the pre-analytical and analytical conditions of the MSD ® method using injured and healthy skin samples, for the purpose of looking for and identifying the cytokine, or the set of cytokines, that may be biomarkers of skin wound vitality.

Effects of fecal sampling on preanalytical and analytical phases in quantitative fecal immunochemical tests for hemoglobin.

PubMed

Rapi, Stefano; Berardi, Margherita; Cellai, Filippo; Ciattini, Samuele; Chelazzi, Laura; Ognibene, Agostino; Rubeca, Tiziana

2017-07-24

Information on preanalytical variability is mandatory to bring laboratories up to ISO 15189 requirements. Fecal sampling is greatly affected by lack of harmonization in laboratory medicine. The aims of this study were to obtain information on the devices used for fecal sampling and to explore the effect of different amounts of feces on the results from the fecal immunochemical test for hemoglobin (FIT-Hb). Four commercial sample collection devices for quantitative FIT-Hb measurements were investigated. The volume of interest (VOI) of the probes was measured from diameter and geometry. Quantitative measurements of the mass of feces were carried out by gravimetry. The effects of an increased amount of feces on the analytical environment were investigated measuring the Hb values with a single analytical method. VOI was 8.22, 7.1 and 9.44 mm3 for probes that collected a target of 10 mg of feces, and 3.08 mm3 for one probe that targeted 2 mg of feces. The ratio between recovered and target amounts of devices ranged from 56% to 121%. Different changes in the measured Hb values were observed, in adding increasing amounts of feces in commercial buffers. The amounts of collected materials are related to the design of probes. Three out 4 manufacturers declare the same target amount using different sampling volumes and obtaining different amounts of collected materials. The introduction of a standard probes to reduce preanalytical variability could be an useful step for fecal test harmonization and to fulfill the ISO 15189 requirements.

Evaluation of pre-analytical conditions and comparison of the performance of several digital PCR assays for the detection of major EGFR mutations in circulating DNA from non-small cell lung cancers: the CIRCAN_0 study

PubMed Central

Garcia, Jessica; Dusserre, Eric; Cheynet, Valérie; Bringuier, Pierre Paul; Brengle-Pesce, Karen; Wozny, Anne-Sophie; Rodriguez-Lafrasse, Claire; Freyer, Gilles; Brevet, Marie; Payen, Léa; Couraud, Sébastien

2017-01-01

Non invasive somatic detection assays are suitable for repetitive tumor characterization or for detecting the appearance of somatic resistance during lung cancer. Molecular diagnosis based on circulating free DNA (cfDNA) offers the opportunity to track the genomic evolution of the tumor, and was chosen to assess the molecular profile of several EGFR alterations, including deletions in exon 19 (delEX19), the L858R substitution on exon 21 and the EGFR resistance mutation T790M on exon 20. Our study aimed at determining optimal pre-analytical conditions and EGFR mutation detection assays for analyzing cfDNA using the picoliter-droplet digital polymerase chain reaction (ddPCR) assay. Within the framework of the CIRCAN project set-up at the Lyon University Hospital, plasma samples were collected to establish a pre-analytical and analytical workflow of cfDNA analysis. We evaluated all of the steps from blood sampling to mutation detection output, including shipping conditions (4H versus 24H in EDTA tubes), the reproducibility of cfDNA extraction, the specificity/sensitivity of ddPCR (using external controls), and the comparison of different PCR assays for the detection of the three most important EGFR hotspots, which highlighted the increased sensitivity of our in-house primers/probes. Hence, we have described a new protocol facilitating the molecular detection of somatic mutations in cancer patients from liquid biopsies, improving their diagnosis and introducing a less traumatic monitoring system during tumor progression. PMID:29152135

42 CFR 493.1200 - Introduction.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (that is, preanalytic, analytic, and postanalytic) as well as general laboratory systems. (b) The...) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Quality System for Nonwaived Testing § 493.1200 Introduction. (a) Each laboratory that performs nonwaived testing must establish and maintain written policies...

Smartphone-based colorimetric ELISA implementation for determination of women's reproductive steroid hormone profiles.

PubMed

Ogirala, Tejaswi; Eapen, Ashley; Salvante, Katrina G; Rapaport, Tomas; Nepomnaschy, Pablo A; Parameswaran, Ash M

2017-10-01

Biologists frequently collect and analyze biospecimens in naturalistic (i.e., field) conditions to ascertain information regarding the physiological status of their study participants. Generally, field-collected biospecimens need to be stored frozen in the field and then transported frozen to laboratory facilities where traditional biomarker assays, such as enzyme-linked immunosorbent assays (ELISAs), are conducted. As proper storage and transport of frozen specimens is often logistically difficult and expensive, particularly in nonurban field settings, methods that reduce the need for specimen storage and transport would benefit field-research dependent disciplines such as biology, ecology and epidemiology. One limiting factor to running assays in the field is the use of large and expensive equipment to visualize and quantify the assays, such as microplate readers. Here, we describe an implementation of colorimetric ELISA visualization and quantification using two novel and portable imaging instrumentation systems and data processing techniques for the determination of women's reproductive steroid hormone profiles. Using the light absorbance and transmittance properties of the chemical compounds that make up the hormone assay, we were able to estimate unknown hormone concentrations using a smartphone system and a webcam system. These estimates were comparable to those from a standard laboratory multiple reader (smartphone: accuracy = 82.20%, R 2  > 0.910; webcam: accuracy = 87.59%, R 2  > 0.942). This line of applied research, in the long run, is expected to provide necessary information for examining the extent to which reproductive function varies within and between populations and how it is influenced by psychosocial, energetic and environmental challenges. Our validation of these novel, portable visualization and quantification systems allows for the eventual development of a compact and economical closed system which can be used to quantify biomarker concentrations in remote areas.

[Tissue repositories for research at Sheba Medical Center(SMC].

PubMed

Cohen, Yehudit; Barshack, Iris; Onn, Amir

2013-06-01

Cancer is the number one cause of death in both genders. Breakthroughs in the understanding of cancer biology, the identification of prognostic factors, and the development of new treatments are increasingly dependent on access to human cancer tissues with linked clinicopathological data. Access to human tumor samples and a large investment in translational research are needed to advance this research. The SMC tissue repositories provide researchers with biological materials, which are essential tools for cancer research. SMC tissue repositories for research aim to collect, document and preserve human biospecimens from patients with cancerous diseases. This is in order to provide the highest quality and well annotated biological biospecimens, used as essential tools to achieve the growing demands of scientific research needs. Such repositories are partners in acceLerating biomedical research and medical product development through clinical resources, in order to apply best options to the patients. Following Institutional Review Board approval and signing an Informed Consent Form, the tumor and tumor-free specimens are coLLected by a designated pathologist at the operating room only when there is a sufficient amount of the tumor, in excess of the routine needs. Blood samples are collected prior to the procedure. Other types of specimens collected include ascites fluid, pleural effusion, tissues for Optimal Cutting Temperature [OCT] and primary culture etc. Demographic, clinical, pathologicaL, and follow-up data are collected in a designated database. SMC has already established several organ or disease-specific tissue repositories within different departments. The foundation of tissue repositories requires the concentrated effort of a multidisciplinary team composed of paramedical, medical and scientific professionals. Research projects using these specimens facilitate the development of 'targeted therapy', accelerate basic research aimed at clarifying molecular mechanisms involved in cancer, and support the development of novel diagnostic tools.

The Establishment of an Inflammatory Breast Cancer Registry and Biospecimen Repository

DTIC Science & Technology

2005-08-01

8217Tamoxifen and Exemestane Triar) study, women will receive an LHRH agonist ( Triptorelin ) immediately after surgery. They will be randomised to...combine Triptorelin with Tamoxifen versus Exemestane. In both the SOFT and the TEXT studies, the new combination of ovarian ablation plus an aromatase

Biorepositories | Division of Cancer Prevention

Cancer.gov

Carefully collected and controlled high-quality human biospecimens, annotated with clinical data and properly consented for investigational use, are available through the Division of Cancer Prevention Biorepositories listed in the charts below. Biorepositories Managed by the Division of Cancer Prevention Biorepositories Supported by the Division of Cancer Prevention Related

76 FR 38191 - New Proposed Collection; Comment Request; Biospecimen and Physical Measures Formative Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... Institute of Child Health and Human Development (NICHD), the National Institutes of Health (NIH) will..., chemical, biological, and psychosocial) on children's health and development. (b) In General.--The Director of the National Institute of Child Health and Human Development* shall establish a consortium of...

NCI International EBV-Gastric Cancer Consortium

Cancer.gov

A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.

Filipino women's diet and health study (FiLWHEL): design and methods.

PubMed

Abris, Grace P; Hong, Sangmo; Provido, Sherlyn Mae P; Lee, Jung Eun; Lee, Chang Beom

2017-02-01

Immigration to South Korea from neighboring Asian countries has risen dramatically, primarily due to marriage between Korean men and foreign women. Although Filipino women rank fourth among married immigrant women, little is known about the health condition of this population. This manuscript focuses on the design and methods of Filipino women's diet and health study (FiLWHEL). FiLWHEL is a cohort of Filipino women married to Korean men, aged 19 years old or over. The data collection comprised three parts: questionnaire, physical examination, and biospecimen collection. Questionnaires focused on demographic factors, diet, other health-related behaviors, acculturation and immigration-related factors, medical history, quality of life, and children's health information. Participants visited the recruitment site and answered the structured questionnaires through a face-to-face interview. We also measured their anthropometric features and collected fasting blood samples, toenails, and DNA samples. Recruitment started in 2014. Collection of data is ongoing, and we plan to prospectively follow our cohort participants. We expect that our study, which is focused on married Filipino women immigrants, can elucidate nutritional/health status and the effects of transitional experiences from several lifestyle factors.

The Benefits and Challenges of an Interfaced Electronic Health Record and Laboratory Information System: Effects on Laboratory Processes.

PubMed

Petrides, Athena K; Bixho, Ida; Goonan, Ellen M; Bates, David W; Shaykevich, Shimon; Lipsitz, Stuart R; Landman, Adam B; Tanasijevic, Milenko J; Melanson, Stacy E F

2017-03-01

- A recent government regulation incentivizes implementation of an electronic health record (EHR) with computerized order entry and structured results display. Many institutions have also chosen to interface their EHR with their laboratory information system (LIS). - To determine the impact of an interfaced EHR-LIS on laboratory processes. - We analyzed several different processes before and after implementation of an interfaced EHR-LIS: the turnaround time, the number of stat specimens received, venipunctures per patient per day, preanalytic errors in phlebotomy, the number of add-on tests using a new electronic process, and the number of wrong test codes ordered. Data were gathered through the LIS and/or EHR. - The turnaround time for potassium and hematocrit decreased significantly (P = .047 and P = .004, respectively). The number of stat orders also decreased significantly, from 40% to 7% for potassium and hematocrit, respectively (P < .001 for both). Even though the average number of inpatient venipunctures per day increased from 1.38 to 1.62 (P < .001), the average number of preanalytic errors per month decreased from 2.24 to 0.16 per 1000 specimens (P < .001). Overall there was a 16% increase in add-on tests. The number of wrong test codes ordered was high and it was challenging for providers to correctly order some common tests. - An interfaced EHR-LIS significantly improved within-laboratory turnaround time and decreased stat requests and preanalytic phlebotomy errors. Despite increasing the number of add-on requests, an electronic add-on process increased efficiency and improved provider satisfaction. Laboratories implementing an interfaced EHR-LIS should be cautious of its effects on test ordering and patient venipunctures per day.

Heparin removal by ecteola-cellulose pre-treatment enables the use of plasma samples for accurate measurement of anti-Yellow fever virus neutralizing antibodies.

PubMed

Campi-Azevedo, Ana Carolina; Peruhype-Magalhães, Vanessa; Coelho-Dos-Reis, Jordana Grazziela; Costa-Pereira, Christiane; Yamamura, Anna Yoshida; Lima, Sheila Maria Barbosa de; Simões, Marisol; Campos, Fernanda Magalhães Freire; de Castro Zacche Tonini, Aline; Lemos, Elenice Moreira; Brum, Ricardo Cristiano; de Noronha, Tatiana Guimarães; Freire, Marcos Silva; Maia, Maria de Lourdes Sousa; Camacho, Luiz Antônio Bastos; Rios, Maria; Chancey, Caren; Romano, Alessandro; Domingues, Carla Magda; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis

2017-09-01

Technological innovations in vaccinology have recently contributed to bring about novel insights for the vaccine-induced immune response. While the current protocols that use peripheral blood samples may provide abundant data, a range of distinct components of whole blood samples are required and the different anticoagulant systems employed may impair some properties of the biological sample and interfere with functional assays. Although the interference of heparin in functional assays for viral neutralizing antibodies such as the functional plaque-reduction neutralization test (PRNT), considered the gold-standard method to assess and monitor the protective immunity induced by the Yellow fever virus (YFV) vaccine, has been well characterized, the development of pre-analytical treatments is still required for the establishment of optimized protocols. The present study intended to optimize and evaluate the performance of pre-analytical treatment of heparin-collected blood samples with ecteola-cellulose (ECT) to provide accurate measurement of anti-YFV neutralizing antibodies, by PRNT. The study was designed in three steps, including: I. Problem statement; II. Pre-analytical steps; III. Analytical steps. Data confirmed the interference of heparin on PRNT reactivity in a dose-responsive fashion. Distinct sets of conditions for ECT pre-treatment were tested to optimize the heparin removal. The optimized protocol was pre-validated to determine the effectiveness of heparin plasma:ECT treatment to restore the PRNT titers as compared to serum samples. The validation and comparative performance was carried out by using a large range of serum vs heparin plasma:ECT 1:2 paired samples obtained from unvaccinated and 17DD-YFV primary vaccinated subjects. Altogether, the findings support the use of heparin plasma:ECT samples for accurate measurement of anti-YFV neutralizing antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

42 CFR 493.1445 - Standard; Laboratory director responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... quality laboratory services for all aspects of test performance, which includes the preanalytic, analytic... result is found to be unacceptable or unsatisfactory; (5) Ensure that the quality control and quality assessment programs are established and maintained to assure the quality of laboratory services provided and...

42 CFR 493.17 - Test categorization.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., analytic or postanalytic phases of the testing. (2) Training and experience—(i) Score 1. (A) Minimal training is required for preanalytic, analytic and postanalytic phases of the testing process; and (B... necessary for analytic test performance. (3) Reagents and materials preparation—(i) Score 1. (A) Reagents...

42 CFR 493.17 - Test categorization.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., analytic or postanalytic phases of the testing. (2) Training and experience—(i) Score 1. (A) Minimal training is required for preanalytic, analytic and postanalytic phases of the testing process; and (B... necessary for analytic test performance. (3) Reagents and materials preparation—(i) Score 1. (A) Reagents...

Identification errors in the blood transfusion laboratory: a still relevant issue for patient safety.

PubMed

Lippi, Giuseppe; Plebani, Mario

2011-04-01

Remarkable technological advances and increased awareness have both contributed to decrease substantially the uncertainty of the analytical phase, so that the manually intensive preanalytical activities currently represent the leading sources of errors in laboratory and transfusion medicine. Among preanalytical errors, misidentification and mistransfusion are still regarded as a considerable problem, posing serious risks for patient health and carrying huge expenses for the healthcare system. As such, a reliable policy of risk management should be readily implemented, developing through a multifaceted approach to prevent or limit the adverse outcomes related to transfusion reactions from blood incompatibility. This strategy encompasses root cause analysis, compliance with accreditation requirements, strict adherence to standard operating procedures, guidelines and recommendations for specimen collection, use of positive identification devices, rejection of potentially misidentified specimens, informatics data entry, query host communication, automated systems for patient identification and sample labeling and an adequate and safe environment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Preanalytical considerations in detection of colorectal cancer in blood serum using Raman molecular imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Treado, Patrick J.; Stewart, Shona D.; Smith, Aaron; Kirschner, Heather; Post, Christopher; Overholt, Bergein F.

2016-03-01

Colorectal cancer (CRC) is the third most common cancer in men and women in the United States. Raman Molecular Imaging (RMI) is an effective technique to evaluate human tissue, cells and bodily fluids, including blood serum for disease diagnosis. ChemImage Corporation, in collaboration with clinicians, has been engaged in development of an in vitro diagnostic Raman assay focused on CRC detection. The Raman Assay for Colorectal Cancer (RACC) exploits the high specificity of Raman imaging to distinguish diseased from normal dried blood serum droplets without additional reagents. Pilot Study results from testing of hundreds of biobank patient samples have demonstrated that RACC detects CRC with high sensitivity and specificity. However, expanded clinical trials, which are ongoing, are revealing a host of important preanalytical considerations associated with sample collection, sample storage and stability, sample shipping, sample preparation and sample interferents, which impact detection performance. Results from recent clinical studies will be presented.

Privacy and equality in diagnostic genetic testing.

PubMed

Nyrhinen, Tarja; Hietala, Marja; Puukka, Pauli; Leino-Kilpi, Helena

2007-05-01

This study aimed to determine the extent to which the principles of privacy and equality were observed during diagnostic genetic testing according to views held by patients or child patients' parents (n = 106) and by staff (n = 162) from three Finnish university hospitals. The data were collected through a structured questionnaire and analysed using the SAS 8.1 statistical software. In general, the two principles were observed relatively satisfactorily in clinical practice. According to patients/parents, equality in the post-analytic phase and, according to staff, privacy in the pre-analytic phase, involved the greatest ethical problems. The two groups differed in their views concerning pre-analytic privacy. Although there were no major problems regarding the two principles, the differences between the testing phases require further clarification. To enhance privacy protection and equality, professionals need to be given more genetics/ethics training, and patients individual counselling by genetics units staff, giving more consideration to patients' world-view, the purpose of the test and the test result.

76 FR 23609 - New Proposed Collection; Comment Request; Biospecimen and Physical Measures Formative Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... has obtained an OMB generic clearance to conduct survey and instrument design and administration... conduct the detailed preparation needed for a study of this size and complexity, the NCS was designed to... methodological studies conducted during the Vanguard phase will inform the implementation and analysis plan for...

76 FR 54474 - Submission for OMB Review; Comment Request New proposed collection, Biospecimen and Physical...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

... authorize the National Institute of Child Health and Human Development* to conduct a national longitudinal... children's health and development. (b) IN GENERAL.--The Director of the National Institute of Child Health... effects of both chronic and intermittent exposures on child health and human development; and (2...

Biobanking for Personalized Medicine.

PubMed

Liu, Angen; Pollard, Kai

2015-01-01

A biobank is an entity that collects, processes, stores, and distributes biospecimens and relevant data for use in basic, translational, and clinical research. Biobanking of high-quality human biospecimens such as tissue, blood and other bodily fluids along with associated patient clinical information provides a fundamental scientific infrastructure for personalized medicine. Identification of biomarkers that are specifically associated with particular medical conditions such as cancer, cardiovascular disease and neurological disorders are useful for early detection, prevention, and treatment of the diseases. The ability to determine individual tumor biomarkers and to use those biomarkers for disease diagnosis, prognosis and prediction of response to therapy is having a very significant impact on personalized medicine and is rapidly changing the way clinical care is conducted. As a critical requirement for personalized medicine is the availability of a large collection of patient samples with well annotated patient clinical and pathological data, biobanks thus play an important role in personalized medicine advancement. The goal of this chapter is to explore the role of biobanks in personalized medicine and discuss specific needs regarding biobank development for translational and clinical research, especially for personalized medicine advancement.

Intratumoral Agreement of High-Resolution Magic Angle Spinning Magnetic Resonance Spectroscopic Profiles in the Metabolic Characterization of Breast Cancer

PubMed Central

Park, Vivian Youngjean; Yoon, Dahye; Koo, Ja Seung; Kim, Eun-Kyung; Kim, Seung Il; Choi, Ji Soo; Park, Seho; Park, Hyung Seok; Kim, Suhkmann; Kim, Min Jung

2016-01-01

Abstract High-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy data may serve as a biomarker for breast cancer, with only a small volume of tissue sample required for assessment. However, previous studies utilized only a single tissue sample from each patient. The aim of this study was to investigate whether intratumoral location and biospecimen type affected the metabolic characterization of breast cancer assessed by HR-MAS MR spectroscopy This prospective study was approved by the institutional review board and informed consent was obtained. Preoperative core-needle biopsies (CNBs), central, and peripheral surgical tumor specimens were prospectively collected under ultrasound (US) guidance in 31 patients with invasive breast cancer. Specimens were assessed with HR-MAS MR spectroscopy. The reliability of metabolite concentrations was evaluated and multivariate analysis was performed according to intratumoral location and biospecimen type. There was a moderate or higher agreement between the relative concentrations of 94.3% (33 of 35) of metabolites in the center and periphery, 80.0% (28 of 35) of metabolites in the CNB and central surgical specimens, and 82.9% (29 of 35) of metabolites between all 3 specimen types. However, there was no significant agreement between the concentrations of phosphocholine (PC) and phosphoethanolamine (PE) in the center and periphery. The concentrations of several metabolites (adipate, arginine, fumarate, glutamate, PC, and PE) had no significant agreement between the CNB and central surgical specimens. In conclusion, most HR-MAS MR spectroscopic data do not differ based on intratumoral location or biospecimen type. However, some metabolites may be affected by specimen-related variables, and caution is recommended in decision-making based solely on metabolite concentrations, particularly PC and PE. Further validation through future studies is needed for the clinical implementation of these biomarkers based on data from a single tissue sample. PMID:27082613

Sustainability in Biobanking: Model of Biobank Graz.

PubMed

Sargsyan, Karine; Macheiner, Tanja; Story, Petra; Strahlhofer-Augsten, Manuela; Plattner, Katharina; Riegler, Skaiste; Granitz, Gabriele; Bayer, Michaela; Huppertz, Berthold

2015-12-01

Research infrastructures remain the key for state-of-the-art and successful research. In the last few decades, biobanks have become increasingly important in this field through standardization of biospecimen processing, sample storage, and standardized data management. Research infrastructure in cohort studies and other sample collection activities are currently experiencing a lack of long-term funding. In this article, the Biobank Graz discusses these aspects of sustainability including the definition of sustainability and necessity of a business plan, as well as cost calculation model in the field of biobanking. The economic state, critical success factors, and important operational issues are reviewed and described by the authors, using the example of the Biobank Graz. Sustainability in the field of biobanking is a globally important matter of necessity, starting from policy making and ending with security and documentation on each operational level.

42 CFR 493.1241 - Standard: Test request.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Standard: Test request. 493.1241 Section 493.1241 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Quality System for Nonwaived Testing Preanalytic Systems § 493.1241 Standard: Test request...

About the Early Detection Research Group | Division of Cancer Prevention

Cancer.gov

The Early Detection Research Group supports research that seeks to determine the effectiveness, operating characteristics and clinical impact (harms as well as benefits) of cancer early detection technologies and practices, such as imaging and molecular biomarker approaches.   The group ran two large-scale early detection trials for which data and biospecimens are available

New Funding Opportunity: Tissue Purchase Order Acquisitions | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute (NCI) is expanding its basic and translational research programs that rely heavily on sufficient availability of high quality, well annotated biospecimens suitable for use in genomic and proteomic studies.  The NCI’s overarching goal with such programs is to improve the ability to diagnose, treat, and prevent cancer.

Interferences from blood collection tube components on clinical chemistry assays

PubMed Central

Bowen, Raffick A.R.; Remaley, Alan T.

2014-01-01

Improper design or use of blood collection devices can adversely affect the accuracy of laboratory test results. Vascular access devices, such as catheters and needles, exert shear forces during blood flow, which creates a predisposition to cell lysis. Components from blood collection tubes, such as stoppers, lubricants, surfactants, and separator gels, can leach into specimens and/or adsorb analytes from a specimen; special tube additives may also alter analyte stability. Because of these interactions with blood specimens, blood collection devices are a potential source of pre-analytical error in laboratory testing. Accurate laboratory testing requires an understanding of the complex interactions between collection devices and blood specimens. Manufacturers, vendors, and clinical laboratorians must consider the pre-analytical challenges in laboratory testing. Although other authors have described the effects of endogenous substances on clinical assay results, the effects/impact of blood collection tube additives and components have not been well systematically described or explained. This review aims to identify and describe blood collection tube additives and their components and the strategies used to minimize their effects on clinical chemistry assays. PMID:24627713

Some imminent but overlooked preanalytical and analytical challenges currently facing biomarkers and companion diagnostics.

PubMed

Halim, Abdel-Baset

2015-06-01

An incredibly high failure rate in the pharmaceutical industry has positioned personalized medicine with its prerequisite drug-diagnostic codevelopment, commonly known as companion diagnostics (CDx), in the frontline as an potential rescuer. This hopefulness is potentiated by the recent major advances and competitiveness in molecular diagnostics, making laboratory tests widely accessible at affordable prices. If executed correctly, biomarkers and CDx can potentially help the drug industry by enhancing the probability of success and possibly accelerating time to market; help the diagnostics industry develop tests utilizing precious, clinically annotated human samples; and, more importantly, benefit patients by supporting accurate diagnosis and selection of the most efficacious and least toxic therapies. However, this spectacular road is not yet paved, and it faces an enormous number of challenges. This paper will list these challenges and highlight some critical problems with representative examples of imminent but still overlooked preanalytical and analytical variables that can defeat the whole purpose of biomarkers and CDx and mislead drug developers and clinicians. The paper will provide some suggestions for mitigation. © 2015 New York Academy of Sciences.

Metabolic profiling of body fluids and multivariate data analysis.

PubMed

Trezzi, Jean-Pierre; Jäger, Christian; Galozzi, Sara; Barkovits, Katalin; Marcus, Katrin; Mollenhauer, Brit; Hiller, Karsten

2017-01-01

Metabolome analyses of body fluids are challenging due pre-analytical variations, such as pre-processing delay and temperature, and constant dynamical changes of biochemical processes within the samples. Therefore, proper sample handling starting from the time of collection up to the analysis is crucial to obtain high quality samples and reproducible results. A metabolomics analysis is divided into 4 main steps: 1) Sample collection, 2) Metabolite extraction, 3) Data acquisition and 4) Data analysis. Here, we describe a protocol for gas chromatography coupled to mass spectrometry (GC-MS) based metabolic analysis for biological matrices, especially body fluids. This protocol can be applied on blood serum/plasma, saliva and cerebrospinal fluid (CSF) samples of humans and other vertebrates. It covers sample collection, sample pre-processing, metabolite extraction, GC-MS measurement and guidelines for the subsequent data analysis. Advantages of this protocol include: •Robust and reproducible metabolomics results, taking into account pre-analytical variations that may occur during the sampling process•Small sample volume required•Rapid and cost-effective processing of biological samples•Logistic regression based determination of biomarker signatures for in-depth data analysis.

Reproducibility studies for experimental epitope detection in macrophages (EDIM).

PubMed

Japink, Dennis; Nap, Marius; Sosef, Meindert N; Nelemans, Patty J; Coy, Johannes F; Beets, Geerard; von Meyenfeldt, Maarten F; Leers, Math P G

2014-05-01

We have recently described epitope detection in macrophages (EDIM) by flow cytometry. This is a promising tool for the diagnosis and follow-up of malignancies. However, biological and technical validation is warranted before clinical applicability can be explored. The pre-analytic and analytic phases were investigated. Five different aspects were assessed: blood sample stability, intra-individual variability in healthy persons, intra-assay variation, inter-assay variation and assay transferability. The post-analytic phase was already partly standardized and described in an earlier study. The outcomes in the pre-analytic phase showed that samples are stable for 24h after venipuncture. Biological variation over time was similar to that of serum tumor marker assays; each patient has a baseline value. Intra-assay variation showed good reproducibility, while inter-assay variation showed reproducibility similar to that of to established serum tumor marker assays. Furthermore, the assay showed excellent transferability between analyzers. Under optimal analytic conditions the EDIM method is technically stable, reproducible and transferable. Biological variation over time needs further assessment in future work. Copyright © 2014 Elsevier B.V. All rights reserved.

Platelet Function Tests: Preanalytical Variables, Clinical Utility, Advantages, and Disadvantages.

PubMed

Hvas, Anne-Mette; Grove, Erik Lerkevang

2017-01-01

Platelet function tests are mainly used in the diagnostic work-up of platelet disorders. During the last decade, the additional use of platelet function tests to evaluate the effect of antiplatelet therapy has also emerged in an attempt to identify patients with an increased risk of arterial thrombosis. Furthermore, platelet function tests are increasingly used to measure residual effect of antiplatelet therapy prior to surgery with the aim of reducing the risk of bleeding. To a limited extend, platelet function tests are also used to evaluate hyperaggregability as a potential marker of a prothrombotic state outside the setting of antiplatelet therapy. This multifaceted use of platelet function tests and the development of simpler point-of-care tests with narrower application have increased the use of platelet function testing and also facilitated the use of platelet function tests outside the highly specialized laboratories. The present chapter describes the preanalytical variables, which should be taken into account when planning platelet function testing. Also, the most widely used platelet function tests are introduced, and their clinical utility and their relative advantages and disadvantages are discussed.

Filipino women's diet and health study (FiLWHEL): design and methods

PubMed Central

Abris, Grace P.; Hong, Sangmo; Provido, Sherlyn Mae P.

2017-01-01

BACKGROUND Immigration to South Korea from neighboring Asian countries has risen dramatically, primarily due to marriage between Korean men and foreign women. Although Filipino women rank fourth among married immigrant women, little is known about the health condition of this population. This manuscript focuses on the design and methods of Filipino women's diet and health study (FiLWHEL). SUBJECTS/METHODS FiLWHEL is a cohort of Filipino women married to Korean men, aged 19 years old or over. The data collection comprised three parts: questionnaire, physical examination, and biospecimen collection. Questionnaires focused on demographic factors, diet, other health-related behaviors, acculturation and immigration-related factors, medical history, quality of life, and children's health information. Participants visited the recruitment site and answered the structured questionnaires through a face-to-face interview. We also measured their anthropometric features and collected fasting blood samples, toenails, and DNA samples. Recruitment started in 2014. RESULTS/CONCLUSIONS Collection of data is ongoing, and we plan to prospectively follow our cohort participants. We expect that our study, which is focused on married Filipino women immigrants, can elucidate nutritional/health status and the effects of transitional experiences from several lifestyle factors. PMID:28194268

Public biobanks: calculation and recovery of costs.

PubMed

Clément, Bruno; Yuille, Martin; Zaltoukal, Kurt; Wichmann, Heinz-Erich; Anton, Gabriele; Parodi, Barbara; Kozera, Lukasz; Bréchot, Christian; Hofman, Paul; Dagher, Georges

2014-11-05

A calculation grid developed by an international expert group was tested across biobanks in six countries to evaluate costs for collections of various types of biospecimens. The assessment yielded a tool for setting specimen-access prices that were transparently related to biobank costs, and the tool was applied across three models of collaborative partnership. Copyright © 2014, American Association for the Advancement of Science.

75 FR 52351 - Submission for OMB Review; Comment Request; Resource for the Collection and Evaluation of Human...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... submitted to the Office of Management and Budget (OMB) a request to review and approve the information... the life styles and exposures and the biospecimens will serve as controls for the assay results... of Management and Budget, at [email protected] or by fax to 202-395-6974. To request more...

Prostate Cancer Biorepository Network

DTIC Science & Technology

2017-10-01

Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704...clinical data including pathology and outcome data are annotated with the biospecimens. Specialized processing consists of tissue microarray design ...Months 1- 6): Completed in 1st quarter Task 5. Report on performance metrics: Ongoing (accrual reports are provided on quarterly basis) Task 6

Funding sources for Canadian biorepositories: the role of user fees and strategies to help fill the gap.

PubMed

Barnes, Rebecca O; Schacter, Brent; Kodeeswaran, Sugy; Watson, Peter H

2014-10-01

Biorepositories, the coordinating hubs for the collection and annotation of biospecimens, are under increasing financial pressure and are challenged to remain sustainable. To gain a better understanding of the current funding situation for Canadian biorepositories and the relative contributions they receive from different funding sources, the Canadian Tumour Repository Network (CTRNet) conducted two surveys. The first survey targeted CTRNet's six main nodes to ascertain the relative funding sources and levels of user fees. The second survey was targeted to a broader range of biorepositories (n=45) to ascertain business practices in application of user fees. The results show that >70% of Canadian biorepositories apply user fees and that the majority apply differential fees to different user groups (academic vs. industry, local vs. international). However, user fees typically comprise only 6% of overall operational budgets. We conclude that while strategies to drive up user fee levels need to be implemented, it is essential for the many stakeholders in the biomedical health research sector to consider this issue in order to ensure the ongoing availability of research biospecimens and data that are standardized, high-quality, and that are therefore capable of meeting research needs.

Development of a consensus approach for return of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project.

PubMed

Lockhart, Nicole C; Weil, Carol J; Carithers, Latarsha J; Koester, Susan E; Little, A Roger; Volpi, Simona; Moore, Helen M; Berkman, Benjamin E

2018-06-14

The active debate about the return of incidental or secondary findings in research has primarily focused on return to research participants, or in some cases, family members. Particular attention has been paid to return of genomic findings. Yet, research may generate other types of findings that warrant consideration for return, including findings related to the pathology of donated biospecimens. In the case of deceased biospecimen donors who are also organ and/or tissue transplant donors, pathology incidental findings may be relevant not to family members, but to potential organ or tissue transplant recipients. This paper will describe the ethical implications of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project, the process for developing a consensus approach as to if/when such findings should be returned, possible implications for other research projects collecting postmortem tissues and how the scenario encountered in GTEx fits into the larger return of results/incidental findings debate. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

NCI Think Tank Concerning the Identifiability of Biospecimens and “-Omic” Data

PubMed Central

Weil, Carol J.; Mechanic, Leah E.; Green, Tiffany; Kinsinger, Christopher; Lockhart, Nicole C.; Nelson, Stefanie A.; Rodriguez, Laura L.; Buccini, Laura D.

2014-01-01

On June 11 and 12, 2012, the National Cancer Institute (NCI) hosted a think tank concerning the identifiability of biospecimens and “omic” Data in order to explore challenges surrounding this complex and multifaceted topic. The think tank brought together forty-six leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics. The first day involved presentations regarding the state of the science of re-identification; current and proposed regulatory frameworks for assessing identifiability; developments in law, industry and biotechnology; and the expectations of patients and research participants. The second day was spent by think tank participants in small break-out groups designed to address specific sub-topics under the umbrella issue of identifiability, including considerations for the development of best practices for data sharing and consent, and targeted opportunities for further empirical research. We describe the outcomes of this two day meeting, including two complimentary themes that emerged from moderated discussions following the presentations on Day 1, and ideas presented for further empirical research to discern the preferences and concerns of research participants about data sharing and individual identifiability. PMID:23579437

Quantitative assessment of effect of preanalytic cold ischemic time on protein expression in breast cancer tissues.

PubMed

Neumeister, Veronique M; Anagnostou, Valsamo; Siddiqui, Summar; England, Allison Michal; Zarrella, Elizabeth R; Vassilakopoulou, Maria; Parisi, Fabio; Kluger, Yuval; Hicks, David G; Rimm, David L

2012-12-05

Companion diagnostic tests can depend on accurate measurement of protein expression in tissues. Preanalytic variables, especially cold ischemic time (time from tissue removal to fixation in formalin) can affect the measurement and may cause false-negative results. We examined 23 proteins, including four commonly used breast cancer biomarker proteins, to quantify their sensitivity to cold ischemia in breast cancer tissues. A series of 93 breast cancer specimens with known time-to-fixation represented in a tissue microarray and a second series of 25 matched pairs of core needle biopsies and breast cancer resections were used to evaluate changes in antigenicity as a function of cold ischemic time. Estrogen receptor (ER), progesterone receptor (PgR), HER2 or Ki67, and 19 other antigens were tested. Each antigen was measured using the AQUA method of quantitative immunofluorescence on at least one series. All statistical tests were two-sided. We found no evidence for loss of antigenicity with time-to-fixation for ER, PgR, HER2, or Ki67 in a 4-hour time window. However, with a bootstrapping analysis, we observed a trend toward loss for ER and PgR, a statistically significant loss of antigenicity for phosphorylated tyrosine (P = .0048), and trends toward loss for other proteins. There was evidence of increased antigenicity in acetylated lysine, AKAP13 (P = .009), and HIF1A (P = .046), which are proteins known to be expressed in conditions of hypoxia. The loss of antigenicity for phosphorylated tyrosine and increase in expression of AKAP13, and HIF1A were confirmed in the biopsy/resection series. Key breast cancer biomarkers show no evidence of loss of antigenicity, although this dataset assesses the relatively short time beyond the 1-hour limit in recent guidelines. Other proteins show changes in antigenicity in both directions. Future studies that extend the time range and normalize for heterogeneity will provide more comprehensive information on preanalytic variation due to cold ischemic time.

Does laboratory automation for the preanalytical phase improve data quality?

PubMed

Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Danese, Elisa; Montagnana, Martina; Brocco, Giorgio; Voi, Monica; Picheth, Geraldo; Guidi, Gian Cesare

2013-10-01

Our aim was to evaluate whether automation for the preanalytical phase improves data quality. Blood from 100 volunteers was collected into two vacuum tubes. One sample from each volunteer was respectively assigned to (G1) traditional processing, starting with centrifugation at 1200 g for 10 min, and (G2) the MODULAR PRE-ANALYTICALS EVO-MPA system. The routine clinical chemistry tests were performed in duplicate on the same instrument Cobas 6000 module. G1 samples were uncapped manually and immediately placed into the instrument. G2 samples were directly fed from the MPA system to the instrument without further staff intervention. At the end, (1) the G1 samples were stored for 6 h at 4 °C as prescribed in our accredited laboratory and (2) the G2 samples were stored for 6 h in the MPA output buffer. Results from G1 and G2, before and after storage, were compared. Significant increases were observed in G1 compared with G2 samples as follows: (1) before storage for alkaline phosphatase (ALP), lactate dehydrogenase (LDH), phosphate (P), magnesium (MG), iron (FE), and hemolysis index and (2) after storage for total cholesterol (COL), triglycerides (TG), total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (CRE), uric acid (UA), ALP, pancreatic amylase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), g-glutamyltransferase (GGT), LDH, creatine kinase (CK), calcium (CA), FE, sodium (NA), potassium (K), and hemolysis index. Moreover, significant increases were observed in (3) G1-after versus G1-before storage samples for COL, high-density lipoprotein cholesterol, TG, TP, ALB, BUN, CRE, UA, AST, ALT, GGT, LDH, P, CA, MG, FE, NA, K, and hemolysis index and (4) G2-after versus G2-before storage only for BUN, AST, LDH, P, and CA. In conclusion, our results show that the MPA system improves the quality of laboratory testing.

Evaluation of a model to improve collection of blood cultures in patients with sepsis in the emergency room.

PubMed

Mariani, B; Corbella, M; Seminari, E; Sacco, L; Cambieri, P; Capra Marzani, F; Martino, I F; Bressan, M A; Muzzi, A; Marena, C; Tinelli, C; Marone, P

2018-02-01

Sepsis begins outside of the hospital for nearly 80% of patients and the emergency room (ER) represents the first contact with the health care system. This study evaluates a project to improve collection of blood cultures (BCs) in patients with sepsis in the ER consisting of staff education and completion of the appropriate BC pre-analytical phase. A retrospective observational study performed to analyse the data on BC collection in the ER before and after a three-phase project. The first phase (1 January to 30 June 2015) before the intervention consisted of evaluation of data on BCs routinely collected in the ER. The second phase (1 July to 31 December 2015) was the intervention phase in which educational courses on sepsis recognition and on pre-analytical phase procedures (including direct incubation) were provided to ER staff. The third phase (1 January to 30 June 2016; after the intervention) again consisted of evaluation. Before the intervention, out of 24,738 admissions to the ER, 103 patients (0.4%) were identified as septic and had BCs drawn (359 BC bottles); 19 out of 103 patients (18.4%) had positive BCs. After the intervention, out of 24,702 admissions, 313 patients (1.3%) had BCs drawn (1,242 bottles); of these, 96 (30.7%) had positive BCs. Comparing the first and third periods, an increase in the percentage of patients with BCs collected (from 0.4% to 1.3% respectively, p < 0.0001) and an increase in the percentages of patients with true-positive BCs (from 0.08% to 0.39% of all patients evaluated respectively, p < 0.0001) were observed. The isolation of bacteria by BCs increased 3.25-fold after project implementation. These results can be principally ascribed to an improved awareness of sepsis in the staff associated with improved pre-analytical phase procedures in BC collection.

Potential misdiagnosis of von Willebrand disease and haemophilia caused by ineffective mixing of thawed plasma.

PubMed

Favaloro, E J; Oliver, S; Mohammed, S; Ahuja, M; Grzechnik, E; Azimulla, S; McDonald, J; Lima-Oliveira, G; Lippi, G

2017-09-01

von Willebrand disease (VWD) reflects a loss or dysfunction in von Willebrand factor (VWF), while haemophilia represents a loss or dysfunction of clotting factors such as factor VIII (FVIII) or FIX. Their diagnosis requires laboratory testing, with this potentially compromised by preanalytical events, including poor sample quality. This study assessed the effect of inadequate mixing as a potential cause of VWD and haemophilia misdiagnosis. After completion of requested testing, 48 consecutive patient samples comprising separate aliquots from single collections were individually pooled, appropriately mixed, then frozen in separate aliquots, either at -20°C or -80°C for 2-7 days. Each sample set was then thawed and the separate aliquots subjected to separate mixing protocols (several inversions, blood roller, vortex) vs a non-mix sample, and all aliquots then tested for various VWF and factor assays. Non-mixing led to substantial reduction in VWF and factors in about 25% of samples, that in some cases could lead to misdiagnosis of VWD or haemophilia. Interestingly, there were also some differences observed with respect to different mixing protocols. Our study identified ineffective or variable mixing of thawed plasma samples as potential causes of misdiagnosis of VWD or haemophilia. Further education regarding the importance of appropriate mixing appears warranted. © 2017 John Wiley & Sons Ltd.

Pre-analytical effects of blood sampling and handling in quantitative immunoassays for rheumatoid arthritis.

PubMed

Zhao, Xiaoyan; Qureshi, Ferhan; Eastman, P Scott; Manning, William C; Alexander, Claire; Robinson, William H; Hesterberg, Lyndal K

2012-04-30

Variability in pre-analytical blood sampling and handling can significantly impact results obtained in quantitative immunoassays. Understanding the impact of these variables is critical for accurate quantification and validation of biomarker measurements. Particularly, in the design and execution of large clinical trials, even small differences in sample processing and handling can have dramatic effects in analytical reliability, results interpretation, trial management and outcome. The effects of two common blood sampling methods (serum vs. plasma) and two widely-used serum handling methods (on the clot with ambient temperature shipping, "traditional", vs. centrifuged with cold chain shipping, "protocol") on protein and autoantibody concentrations were examined. Matched serum and plasma samples were collected from 32 rheumatoid arthritis (RA) patients representing a wide range of disease activity status. Additionally, a set of matched serum samples with two sample handling methods was collected. One tube was processed per manufacturer's instructions and shipped overnight on cold packs (protocol). The matched tube, without prior centrifugation, was simultaneously shipped overnight at ambient temperatures (traditional). Upon delivery, the traditional tube was centrifuged. All samples were subsequently aliquoted and frozen prior to analysis of protein and autoantibody biomarkers. Median correlation between paired serum and plasma across all autoantibody assays was 0.99 (0.98-1.00) with a median % difference of -3.3 (-7.5 to 6.0). In contrast, observed protein biomarker concentrations were significantly affected by sample types, with median correlation of 0.99 (0.33-1.00) and a median % difference of -10 (-55 to 23). When the two serum collection/handling methods were compared, the median correlation between paired samples for autoantibodies was 0.99 (0.91-1.00) with a median difference of 4%. In contrast, significant increases were observed in protein biomarker concentrations among certain biomarkers in samples processed with the 'traditional' method. Autoantibody quantification appears robust to both sample type (plasma vs. serum) and pre-analytical sample collection/handling methods (protocol vs. traditional). In contrast, for non-antibody protein biomarker concentrations, sample type had a significant impact; plasma samples generally exhibit decreased protein biomarker concentrations relative to serum. Similarly, sample handling significantly impacted the variability of protein biomarker concentrations. When biomarker concentrations are combined algorithmically into a single test score such as a multi-biomarker disease activity test for rheumatoid arthritis (MBDA), changes in protein biomarker concentrations may result in a bias of the score. These results illustrate the importance of characterizing pre-analytical methodology, sample type, sample processing and handling procedures for clinical testing in order to ensure test accuracy. Copyright © 2012 Elsevier B.V. All rights reserved.

Prostate Cancer Biospecimen Cohort Study

DTIC Science & Technology

2017-10-01

opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army...SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES...14. ABSTRACT The goal of the study is development of a Prostate Cancer Biorepository Network (PCBN) resource site with high quality and well

Prostate Cancer Biospecimen Cohort Study

DTIC Science & Technology

2016-10-01

goal of the study is development of a Prostate Cancer Biorepository Network (PCBN) resource site with high quality and well-annotated urine , blood...with no coordinating center and each site will be responsible for maintaining/storing their own data/ samples . 15. SUBJECT TERMS Prostate cancer...Biorepository Network (PCBN) resource site with high quality and well-annotated urine , blood, and tissue specimens as part of a multi-institutional Department of

iss047e066248

NASA Image and Video Library

2016-04-19

ISS047e066248 (04/19/2016) --- NASA astronaut and Expedition 47 Flight Engineer Jeff Williams works with the Wet Lab RNA SmartCycler on-board the International Space Station. Wetlab RNA SmartCycler is a research platform for conducting real-time quantitative gene expression analysis aboard the ISS. The system enables spaceflight genomic studies involving a wide variety of biospecimen types in the unique microgravity environment of space.

Security controls in an integrated Biobank to protect privacy in data sharing: rationale and study design.

PubMed

Takai-Igarashi, Takako; Kinoshita, Kengo; Nagasaki, Masao; Ogishima, Soichi; Nakamura, Naoki; Nagase, Sachiko; Nagaie, Satoshi; Saito, Tomo; Nagami, Fuji; Minegishi, Naoko; Suzuki, Yoichi; Suzuki, Kichiya; Hashizume, Hiroaki; Kuriyama, Shinichi; Hozawa, Atsushi; Yaegashi, Nobuo; Kure, Shigeo; Tamiya, Gen; Kawaguchi, Yoshio; Tanaka, Hiroshi; Yamamoto, Masayuki

2017-07-06

With the goal of realizing genome-based personalized healthcare, we have developed a biobank that integrates personal health, genome, and omics data along with biospecimens donated by volunteers of 150,000. Such a large-scale of data integration involves obvious risks of privacy violation. The research use of personal genome and health information is a topic of global discussion with regard to the protection of privacy while promoting scientific advancement. The present paper reports on our plans, current attempts, and accomplishments in addressing security problems involved in data sharing to ensure donor privacy while promoting scientific advancement. Biospecimens and data have been collected in prospective cohort studies with the comprehensive agreement. The sample size of 150,000 participants was required for multiple researches including genome-wide screening of gene by environment interactions, haplotype phasing, and parametric linkage analysis. We established the T ohoku M edical M egabank (TMM) data sharing policy: a privacy protection rule that requires physical, personnel, and technological safeguards against privacy violation regarding the use and sharing of data. The proposed policy refers to that of NCBI and that of the Sanger Institute. The proposed policy classifies shared data according to the strength of re-identification risks. Local committees organized by TMM evaluate re-identification risk and assign a security category to a dataset. Every dataset is stored in an assigned segment of a supercomputer in accordance with its security category. A security manager should be designated to handle all security problems at individual data use locations. The proposed policy requires closed networks and IP-VPN remote connections. The mission of the biobank is to distribute biological resources most productively. This mission motivated us to collect biospecimens and health data and simultaneously analyze genome/omics data in-house. The biobank also has the mission of improving the quality and quantity of the contents of the biobank. This motivated us to request users to share the results of their research as feedback to the biobank. The TMM data sharing policy has tackled every security problem originating with the missions. We believe our current implementation to be the best way to protect privacy in data sharing.

Effectiveness of Preanalytic Practices on Contamination and Diagnostic Accuracy of Urine Cultures: a Laboratory Medicine Best Practices Systematic Review and Meta-analysis

PubMed Central

Franek, Jacob; Leibach, Elizabeth K.; Weissfeld, Alice S.; Kraft, Colleen S.; Sautter, Robert L.; Baselski, Vickie; Rodahl, Debra; Peterson, Edward J.; Cornish, Nancy E.

2015-01-01

SUMMARY Background. Urinary tract infection (UTI) in the United States is the most common bacterial infection, and urine cultures often make up the largest portion of workload for a hospital-based microbiology laboratory. Appropriately managing the factors affecting the preanalytic phase of urine culture contributes significantly to the generation of meaningful culture results that ultimately affect patient diagnosis and management. Urine culture contamination can be reduced with proper techniques for urine collection, preservation, storage, and transport, the major factors affecting the preanalytic phase of urine culture. Objectives. The purposes of this review were to identify and evaluate preanalytic practices associated with urine specimens and to assess their impact on the accuracy of urine culture microbiology. Specific practices included collection methods for men, women, and children; preservation of urine samples in boric acid solutions; and the effect of refrigeration on stored urine. Practice efficacy and effectiveness were measured by two parameters: reduction of urine culture contamination and increased accuracy of patient diagnosis. The CDC Laboratory Medicine Best Practices (LMBP) initiative's systematic review method for assessment of quality improvement (QI) practices was employed. Results were then translated into evidence-based practice guidelines. Search strategy. A search of three electronic bibliographic databases (PubMed, SCOPUS, and CINAHL), as well as hand searching of bibliographies from relevant information sources, for English-language articles published between 1965 and 2014 was conducted. Selection criteria. The search contained the following medical subject headings and key text words: urinary tract infections, UTI, urine/analysis, urine/microbiology, urinalysis, specimen handling, preservation, biological, preservation, boric acid, boric acid/borate, refrigeration, storage, time factors, transportation, transport time, time delay, time factor, timing, urine specimen collection, catheters, indwelling, urinary reservoirs, continent, urinary catheterization, intermittent urethral catheterization, clean voided, midstream, Foley, suprapubic, bacteriological techniques, and microbiological techniques. Main results. Both boric acid and refrigeration adequately preserved urine specimens prior to their processing for up to 24 h. Urine held at room temperature for more than 4 h showed overgrowth of both clinically significant and contaminating microorganisms. The overall strength of this body of evidence, however, was rated as low. For urine specimens collected from women, there was no difference in rates of contamination for midstream urine specimens collected with or without cleansing. The overall strength of this evidence was rated as high. The levels of diagnostic accuracy of midstream urine collection with or without cleansing were similar, although the overall strength of this evidence was rated as low. For urine specimens collected from men, there was a reduction in contamination in favor of midstream clean-catch over first-void specimen collection. The strength of this evidence was rated as high. Only one study compared midstream collection with cleansing to midstream collection without cleansing. Results showed no difference in contamination between the two methods of collection. However, imprecision was due largely to the small event size. The diagnostic accuracy of midstream urine collection from men compared to straight catheterization or suprapubic aspiration was high. However, the overall strength of this body of evidence was rated as low. For urine specimens collected from children and infants, the evidence comparing contamination rates for midstream urine collection with cleansing, midstream collection without cleansing, sterile urine bag collection, and diaper collection pointed to larger reductions in the odds of contamination in favor of midstream collection with cleansing over the other methods of collection. This body of evidence was rated as high. The accuracy of diagnosis of urinary tract infection from midstream clean-catch urine specimens, sterile urine bag specimens, or diaper specimens compared to straight catheterization or suprapubic aspiration was varied. Authors' conclusions. No recommendation for or against is made for delayed processing of urine stored at room temperature, refrigerated, or preserved in boric acid. This does not preclude the use of refrigeration or chemical preservatives in clinical practice. It does indicate, however, that more systematic studies evaluating the utility of these measures are needed. If noninvasive collection is being considered for women, midstream collection with cleansing is recommended, but no recommendation for or against is made for midstream collection without cleansing. If noninvasive collection is being considered for men, midstream collection with cleansing is recommended and collection of first-void urine is not recommended. No recommendation for or against is made for collection of midstream urine without cleansing. If noninvasive collection is being considered for children, midstream collection with cleansing is recommended and collection in sterile urine bags, from diapers, or midstream without cleansing is not recommended. Whether midstream collection with cleansing can be routinely used in place of catheterization or suprapubic aspiration is unclear. The data suggest that midstream collection with cleansing is accurate for the diagnosis of urinary tract infections in infants and children and has higher average accuracy than sterile urine bag collection (data for diaper collection were lacking); however, the overall strength of evidence was low, as multivariate modeling could not be performed, and thus no recommendation for or against can be made. PMID:26598386

Pre-Analytical Conditions in Non-Invasive Prenatal Testing of Cell-Free Fetal RHD

PubMed Central

Rieneck, Klaus; Krog, Grethe Risum; Nielsen, Leif Kofoed; Tabor, Ann; Dziegiel, Morten Hanefeld

2013-01-01

Background Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women. In Denmark, routine antenatal screening for the fetal RhD gene (RHD) directs the administration of antenatal anti-D prophylaxis only to women who carry an RhD positive fetus. Prophylaxis reduces the risk of immunization that may lead to hemolytic disease of the fetus and the newborn. The reliability of predicting the fetal RhD type depends on pre-analytical factors and assay sensitivity. We evaluated the testing setup in the Capital Region of Denmark, based on data from routine antenatal RHD screening. Methods Blood samples were drawn at gestational age 25 weeks. DNA extracted from 1 mL of plasma was analyzed for fetal RHD using a duplex method for exon 7/10. We investigated the effect of blood sample transportation time (n = 110) and ambient outdoor temperatures (n = 1539) on the levels of cffDNA and total DNA. We compared two different quantification methods, the delta Ct method and a universal standard curve. PCR pipetting was compared on two systems (n = 104). Results The cffDNA level was unaffected by blood sample transportation for up to 9 days and by ambient outdoor temperatures ranging from -10°C to 28°C during transport. The universal standard curve was applicable for cffDNA quantification. Identical levels of cffDNA were observed using the two automated PCR pipetting systems. We detected a mean of 100 fetal DNA copies/mL at a median gestational age of 25 weeks (range 10–39, n = 1317). Conclusion The setup for real-time PCR-based, non-invasive prenatal testing of cffDNA in the Capital Region of Denmark is very robust. Our findings regarding the transportation of blood samples demonstrate the high stability of cffDNA. The applicability of a universal standard curve facilitates easy cffDNA quantification. PMID:24204719

Errors in clinical laboratories or errors in laboratory medicine?

PubMed

Plebani, Mario

2006-01-01

Laboratory testing is a highly complex process and, although laboratory services are relatively safe, they are not as safe as they could or should be. Clinical laboratories have long focused their attention on quality control methods and quality assessment programs dealing with analytical aspects of testing. However, a growing body of evidence accumulated in recent decades demonstrates that quality in clinical laboratories cannot be assured by merely focusing on purely analytical aspects. The more recent surveys on errors in laboratory medicine conclude that in the delivery of laboratory testing, mistakes occur more frequently before (pre-analytical) and after (post-analytical) the test has been performed. Most errors are due to pre-analytical factors (46-68.2% of total errors), while a high error rate (18.5-47% of total errors) has also been found in the post-analytical phase. Errors due to analytical problems have been significantly reduced over time, but there is evidence that, particularly for immunoassays, interference may have a serious impact on patients. A description of the most frequent and risky pre-, intra- and post-analytical errors and advice on practical steps for measuring and reducing the risk of errors is therefore given in the present paper. Many mistakes in the Total Testing Process are called "laboratory errors", although these may be due to poor communication, action taken by others involved in the testing process (e.g., physicians, nurses and phlebotomists), or poorly designed processes, all of which are beyond the laboratory's control. Likewise, there is evidence that laboratory information is only partially utilized. A recent document from the International Organization for Standardization (ISO) recommends a new, broader definition of the term "laboratory error" and a classification of errors according to different criteria. In a modern approach to total quality, centered on patients' needs and satisfaction, the risk of errors and mistakes in pre- and post-examination steps must be minimized to guarantee the total quality of laboratory services.

Pre-analytical conditions in non-invasive prenatal testing of cell-free fetal RHD.

PubMed

Clausen, Frederik Banch; Jakobsen, Tanja Roien; Rieneck, Klaus; Krog, Grethe Risum; Nielsen, Leif Kofoed; Tabor, Ann; Dziegiel, Morten Hanefeld

2013-01-01

Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women. In Denmark, routine antenatal screening for the fetal RhD gene (RHD) directs the administration of antenatal anti-D prophylaxis only to women who carry an RhD positive fetus. Prophylaxis reduces the risk of immunization that may lead to hemolytic disease of the fetus and the newborn. The reliability of predicting the fetal RhD type depends on pre-analytical factors and assay sensitivity. We evaluated the testing setup in the Capital Region of Denmark, based on data from routine antenatal RHD screening. Blood samples were drawn at gestational age 25 weeks. DNA extracted from 1 mL of plasma was analyzed for fetal RHD using a duplex method for exon 7/10. We investigated the effect of blood sample transportation time (n = 110) and ambient outdoor temperatures (n = 1539) on the levels of cffDNA and total DNA. We compared two different quantification methods, the delta Ct method and a universal standard curve. PCR pipetting was compared on two systems (n = 104). The cffDNA level was unaffected by blood sample transportation for up to 9 days and by ambient outdoor temperatures ranging from -10 °C to 28 °C during transport. The universal standard curve was applicable for cffDNA quantification. Identical levels of cffDNA were observed using the two automated PCR pipetting systems. We detected a mean of 100 fetal DNA copies/mL at a median gestational age of 25 weeks (range 10-39, n = 1317). The setup for real-time PCR-based, non-invasive prenatal testing of cffDNA in the Capital Region of Denmark is very robust. Our findings regarding the transportation of blood samples demonstrate the high stability of cffDNA. The applicability of a universal standard curve facilitates easy cffDNA quantification.

Outcomes in transfusion.

PubMed

Sherman, L A

1999-07-01

Outcomes data in medicine can be limited by subjective methodologic issues such as poor selection of end points and use of nonvalidated systems for quality adjustment. Blood transfusion analyses are further complicated by the fact that transfusion seldom is primary therapy but is usually supportive or adjunctive. Thus, much of the outcome data in transfusion medicine are either unavailable or in one of two areas. The first area is prevention of bad sequelae of various cytopenias or factor deficiencies. The second is decreasing adverse effects of transfusion itself. A different useful area for outcome and root cause approaches in individual institutions is examining preanalytical and postanalytical processes of their own. Examples are sample labeling accuracy, quality and timeliness of blood suppliers, internal delivery processes and times, and product wastage. Use review can be changed to real time from retrospective time. By reducing complaints about service to objective data, realistic change can be made in internal and external processes.

Methodological Variables in the Analysis of Cell-Free DNA.

PubMed

Bronkhorst, Abel Jacobus; Aucamp, Janine; Pretorius, Piet J

2016-01-01

In recent years, cell-free DNA (cfDNA) analysis has received increasing amounts of attention as a potential non-invasive screening tool for the early detection of genetic aberrations and a wide variety of diseases, especially cancer. However, except for some prenatal tests and BEAMing, a technique used to detect mutations in various genes of cancer patients, cfDNA analysis is not yet routinely applied in clinical practice. Although some confusing biological factors inherent to the in vivo setting play a key part, it is becoming increasingly clear that this struggle is mainly due to the lack of an analytical consensus, especially as regards quantitative analyses of cfDNA. In order to use quantitative analysis of cfDNA with confidence, process optimization and standardization are crucial. In this work we aim to elucidate the most confounding variables of each preanalytical step that must be considered for process optimization and equivalence of procedures.

42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

Code of Federal Regulations, 2011 CFR

2011-10-01

... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

Code of Federal Regulations, 2012 CFR

2012-10-01

... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

Code of Federal Regulations, 2013 CFR

2013-10-01

... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

Code of Federal Regulations, 2014 CFR

2014-10-01

... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

Code of Federal Regulations, 2010 CFR

2010-10-01

... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

The focus on sample quality: Influence of colon tissue collection on reliability of qPCR data

PubMed Central

Korenkova, Vlasta; Slyskova, Jana; Novosadova, Vendula; Pizzamiglio, Sara; Langerova, Lucie; Bjorkman, Jens; Vycital, Ondrej; Liska, Vaclav; Levy, Miroslav; Veskrna, Karel; Vodicka, Pavel; Vodickova, Ludmila; Kubista, Mikael; Verderio, Paolo

2016-01-01

Successful molecular analyses of human solid tissues require intact biological material with well-preserved nucleic acids, proteins, and other cell structures. Pre-analytical handling, comprising of the collection of material at the operating theatre, is among the first critical steps that influence sample quality. The aim of this study was to compare the experimental outcomes obtained from samples collected and stored by the conventional means of snap freezing and by PAXgene Tissue System (Qiagen). These approaches were evaluated by measuring rRNA and mRNA integrity of the samples (RNA Quality Indicator and Differential Amplification Method) and by gene expression profiling. The collection procedures of the biological material were implemented in two hospitals during colon cancer surgery in order to identify the impact of the collection method on the experimental outcome. Our study shows that the pre-analytical sample handling has a significant effect on the quality of RNA and on the variability of qPCR data. PAXgene collection mode proved to be more easily implemented in the operating room and moreover the quality of RNA obtained from human colon tissues by this method is superior to the one obtained by snap freezing. PMID:27383461

Croatian Society of Medical Biochemistry and Laboratory Medicine: national recommendations for venous blood sampling

PubMed Central

Nikolac, Nora; Šupak-Smolčić, Vesna; Šimundić, Ana-Maria; Ćelap, Ivana

2013-01-01

Phlebotomy is one of the most complex medical procedures in the diagnosis, management and treatment of patients in healthcare. Since laboratory test results are the basis for a large proportion (60–80%) of medical decisions, any error in the phlebotomy process could have serious consequences. In order to minimize the possibility of errors, phlebotomy procedures should be standardised, well-documented and written instructions should be available at every workstation. Croatia is one of the few European countries that have national guidelines for phlebotomy, besides the universally used CLSI (Clinical Laboratory Standards Institute) H3-A6 Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture; approved Standard-Sixth Edition (CLSI, 2007) and WHO (World Health Organization) guidelines on drawing blood: best practices in phlebotomy (WHO, 2010). However, the growing body of evidence in importance of preanalytical phase management resulted in a need for evidence based revision and expansion of existing recommendations. The Croatian Society for Medical Biochemistry and Laboratory Medicine, Working Group for the Preanalytical Phase issued this recommendation. This document is based on the CLSI guideline H3-A6, with significant differences and additional information. PMID:24266294

Recognizing and Reducing Analytical Errors and Sources of Variation in Clinical Pathology Data in Safety Assessment Studies.

PubMed

Schultze, A E; Irizarry, A R

2017-02-01

Veterinary clinical pathologists are well positioned via education and training to assist in investigations of unexpected results or increased variation in clinical pathology data. Errors in testing and unexpected variability in clinical pathology data are sometimes referred to as "laboratory errors." These alterations may occur in the preanalytical, analytical, or postanalytical phases of studies. Most of the errors or variability in clinical pathology data occur in the preanalytical or postanalytical phases. True analytical errors occur within the laboratory and are usually the result of operator or instrument error. Analytical errors are often ≤10% of all errors in diagnostic testing, and the frequency of these types of errors has decreased in the last decade. Analytical errors and increased data variability may result from instrument malfunctions, inability to follow proper procedures, undetected failures in quality control, sample misidentification, and/or test interference. This article (1) illustrates several different types of analytical errors and situations within laboratories that may result in increased variability in data, (2) provides recommendations regarding prevention of testing errors and techniques to control variation, and (3) provides a list of references that describe and advise how to deal with increased data variability.

A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies

PubMed Central

Jobard, Elodie; Trédan, Olivier; Postoly, Déborah; André, Fabrice; Martin, Anne-Laure; Elena-Herrmann, Bénédicte; Boyault, Sandrine

2016-01-01

The recent thriving development of biobanks and associated high-throughput phenotyping studies requires the elaboration of large-scale approaches for monitoring biological sample quality and compliance with standard protocols. We present a metabolomic investigation of human blood samples that delineates pitfalls and guidelines for the collection, storage and handling procedures for serum and plasma. A series of eight pre-processing technical parameters is systematically investigated along variable ranges commonly encountered across clinical studies. While metabolic fingerprints, as assessed by nuclear magnetic resonance, are not significantly affected by altered centrifugation parameters or delays between sample pre-processing (blood centrifugation) and storage, our metabolomic investigation highlights that both the delay and storage temperature between blood draw and centrifugation are the primary parameters impacting serum and plasma metabolic profiles. Storing the blood drawn at 4 °C is shown to be a reliable routine to confine variability associated with idle time prior to sample pre-processing. Based on their fine sensitivity to pre-analytical parameters and protocol variations, metabolic fingerprints could be exploited as valuable ways to determine compliance with standard procedures and quality assessment of blood samples within large multi-omic clinical and translational cohort studies. PMID:27929400

Croatian Society of Medical Biochemistry and Laboratory Medicine: national recommendations for venous blood sampling.

PubMed

Nikolac, Nora; Supak-Smolcić, Vesna; Simundić, Ana-Maria; Celap, Ivana

2013-01-01

Phlebotomy is one of the most complex medical procedures in the diagnosis, management and treatment of patients in healthcare. Since laboratory test results are the basis for a large proportion (60-80%) of medical decisions, any error in the phlebotomy process could have serious consequences. In order to minimize the possibility of errors, phlebotomy procedures should be standardised, well-documented and written instructions should be available at every workstation. Croatia is one of the few European countries that have national guidelines for phlebotomy, besides the universally used CLSI (Clinical Laboratory Standards Institute) H3-A6 Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture; approved Standard-Sixth Edition (CLSI, 2007) and WHO (World Health Organization) guidelines on drawing blood: best practices in phlebotomy (WHO, 2010). However, the growing body of evidence in importance of preanalytical phase management resulted in a need for evidence based revision and expansion of existing recommendations. The Croatian Society for Medical Biochemistry and Laboratory Medicine, Working Group for the Preanalytical Phase issued this recommendation. This document is based on the CLSI guideline H3-A6, with significant differences and additional information.

Mistakes in a stat laboratory: types and frequency.

PubMed

Plebani, M; Carraro, P

1997-08-01

Application of Total Quality Management concepts to laboratory testing requires that the total process, including preanalytical and postanalytical phases, be managed so as to reduce or, ideally, eliminate all defects within the process itself. Indeed a "mistake" can be defined as any defect during the entire testing process, from ordering tests to reporting results. We evaluated the frequency and types of mistakes found in the "stat" section of the Department of Laboratory Medicine of the University-Hospital of Padova by monitoring four different departments (internal medicine, nephrology, surgery, and intensive care unit) for 3 months. Among a total of 40490 analyses, we identified 189 laboratory mistakes, a relative frequency of 0.47%. The distribution of mistakes was: preanalytical 68.2%, analytical 13.3%, and postanalytical 18.5%. Most of the laboratory mistakes (74%) did not affect patients' outcome. However, in 37 patients (19%), laboratory mistakes were associated with further inappropriate investigations, thus resulting in an unjustifiable increase in costs. Moreover, in 12 patients (6.4%) laboratory mistakes were associated with inappropriate care or inappropriate modification of therapy. The promotion of quality control and continuous improvement of the total testing process, including pre- and postanalytical phases, seems to be a prerequisite for an effective laboratory service.

GI-POP: a combinational annotation and genomic island prediction pipeline for ongoing microbial genome projects.

PubMed

Lee, Chi-Ching; Chen, Yi-Ping Phoebe; Yao, Tzu-Jung; Ma, Cheng-Yu; Lo, Wei-Cheng; Lyu, Ping-Chiang; Tang, Chuan Yi

2013-04-10

Sequencing of microbial genomes is important because of microbial-carrying antibiotic and pathogenetic activities. However, even with the help of new assembling software, finishing a whole genome is a time-consuming task. In most bacteria, pathogenetic or antibiotic genes are carried in genomic islands. Therefore, a quick genomic island (GI) prediction method is useful for ongoing sequencing genomes. In this work, we built a Web server called GI-POP (http://gipop.life.nthu.edu.tw) which integrates a sequence assembling tool, a functional annotation pipeline, and a high-performance GI predicting module, in a support vector machine (SVM)-based method called genomic island genomic profile scanning (GI-GPS). The draft genomes of the ongoing genome projects in contigs or scaffolds can be submitted to our Web server, and it provides the functional annotation and highly probable GI-predicting results. GI-POP is a comprehensive annotation Web server designed for ongoing genome project analysis. Researchers can perform annotation and obtain pre-analytic information include possible GIs, coding/non-coding sequences and functional analysis from their draft genomes. This pre-analytic system can provide useful information for finishing a genome sequencing project. Copyright © 2012 Elsevier B.V. All rights reserved.

Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

DTIC Science & Technology

2014-12-01

airway epithelium [1, 6, 7], and 2) these changes can be detected and serve as biomarker for early detection of lung cancer [8, 9], in the current...biospecimens from seven locations: nasal epithelium , proximal and distal bronchial airway epithelium obtained at bronchoscopy (ipsilateral and...contralateral to the tumor) as well as the tumor/benign lesion, adjacent normal parenchyma, and sub- segmental bronchial epithelium at time of lobectomy

CPTAC Biospecimen Collection Solicitation | Office of Cancer Clinical Proteomics Research

Cancer.gov

A funding opportunity in support of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) seeks to prospectively procure tumor samples, collected for proteomics investigation. The scope of work under this Statement of Work encompasses the activities needed to prospectively procure high quality, clinically annotated human tumor samples, blood and plasma, and when feasible, normal tissue from volunteer patients suffering from colon, ovarian, and breast cancer.

The Establishment of an Inflammatory Breast Cancer Registry and Biospecimen Repository

DTIC Science & Technology

2004-08-01

will be presented at the San Antonio Breast Cancer Conference in December, 2004. The clinical data include the observation that approximately one third...of IBC patients are initially diagnosed as having mastitis and are treated with up to five months of antibiotics before the diagnosis of cancer is...developed a national registry of patients with IBC which contains standardized clinical , epidemiological and pathological information. Our registry includes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gregory Reaman

The initiative will enable the COG Biopathology Center (Biospecimen Repository), the Molecular Genetics Laboratory and other participating reference laboratories to upload large data sets to the eRDES. The capability streamlines data currency and accuracy allowing the centers to export data from local systems and import the defined data to the eRDES. The process will aid in the best practices which have been defined by the Office of Biorepository and Biospecimen Research (OBBR) and the Group Banking Committee (GBC). The initiative allows for batch import and export, a data validation process and reporting mechanism, and a model for other labs tomore » incorporate. All objectives are complete. The solutions provided and the defined process eliminates dual data entry resulting in data consistency. The audit trail capabilities allow for complete tracking of the data exchange between laboratories and the Statistical Data Center (SDC). The impact is directly on time and efforts. In return, the process will save money and improve the data utilized by the COG. Ongoing efforts include implementing new technologies to further enhance the current solutions and process currently in place. Web Services and Reporting Services are technologies that have become industry standards and will allow for further harmonization with caBIG (cancer Biolnforrnatics Grid). Additional testing and implementation of the model for other laboratories is in process.« less

Fee-for-service as a business model of growing importance: the academic biobank experience.

PubMed

McDonald, Sandra A; Sommerkamp, Kara; Egan-Palmer, Maureen; Kharasch, Karen; Holtschlag, Victoria

2012-10-01

Biorepositories offer tremendous scientific value to a wide variety of customer groups (academic, commercial, industrial) in their ability to deliver a centralized, standardized service model, encompassing both biospecimen storage and related laboratory services. Generally, the scientific expertise and economies of scale that are offered in centralized, properly resourced research biobanks has yielded value that has been well-recognized by universities, pharmaceutical companies, and other sponsoring institutions. However, like many facets of the economy, biobanks have been under increasing cost pressure in recent years. This has been a particular problem in the academic arena, where direct support from grant sources (both governmental and philanthropic) typically now is more difficult to secure, or provides reduced financial support, relative to previous years. One way to address this challenge is to establish or enhance a well-defined fee-for-service model which is properly calibrated to cover operational costs while still offering competitive value to users. In this model, customers are never charged for the biospecimens themselves, but rather for the laboratory services associated with them. Good communication practices, proper assessment of value, implementation of best practices, and a sound business plan are all needed for this initiative to succeed. Here we summarize our experiences at Washington University School of Medicine in the expectation they will be useful to others.

Willingness to Participate in a National Precision Medicine Cohort: Attitudes of Chronic Kidney Disease Patients at a Cleveland Public Hospital.

PubMed

Cooke Bailey, Jessica N; Crawford, Dana C; Goldenberg, Aaron; Slaven, Anne; Pencak, Julie; Schachere, Marleen; Bush, William S; Sedor, John R; O'Toole, John F

2018-06-26

Multiple ongoing, government-funded national efforts longitudinally collect health data and biospecimens for precision medicine research with ascertainment strategies increasingly emphasizing underrepresented groups in biomedical research. We surveyed chronic kidney disease patients from an academic, public integrated tertiary care system in Cleveland, Ohio, to examine local attitudes toward participation in large-scale government-funded studies. Responses ( n = 103) indicate the majority (71%) would participate in a hypothetical national precision medicine cohort and were willing to send biospecimens to a national repository and share de-identified data, but <50% of respondents were willing to install a phone app to track personal data. The majority of participants (62%) indicated that return of research results was very important, and the majority (54%) also wanted all of their research-collected health and genetic data returned. Response patterns did not differ by race/ethnicity. Overall, we found high willingness to participate among this Cleveland patient population already participating in a local genetic study. These data suggest that despite common perceptions, subjects from communities traditionally underrepresented in genetic research will participate and agree to store samples and health data in repositories. Furthermore, most participants want return of research results, which will require a plan to provide these data in a secure, accessible, and understandable manner.

Baobab Laboratory Information Management System: Development of an Open-Source Laboratory Information Management System for Biobanking

PubMed Central

Bendou, Hocine; Sizani, Lunga; Reid, Tim; Swanepoel, Carmen; Ademuyiwa, Toluwaleke; Merino-Martinez, Roxana; Meuller, Heimo; Abayomi, Akin

2017-01-01

A laboratory information management system (LIMS) is central to the informatics infrastructure that underlies biobanking activities. To date, a wide range of commercial and open-source LIMSs are available and the decision to opt for one LIMS over another is often influenced by the needs of the biobank clients and researchers, as well as available financial resources. The Baobab LIMS was developed by customizing the Bika LIMS software (www.bikalims.org) to meet the requirements of biobanking best practices. The need to implement biobank standard operation procedures as well as stimulate the use of standards for biobank data representation motivated the implementation of Baobab LIMS, an open-source LIMS for Biobanking. Baobab LIMS comprises modules for biospecimen kit assembly, shipping of biospecimen kits, storage management, analysis requests, reporting, and invoicing. The Baobab LIMS is based on the Plone web-content management framework. All the system requirements for Plone are applicable to Baobab LIMS, including the need for a server with at least 8 GB RAM and 120 GB hard disk space. Baobab LIMS is a server–client-based system, whereby the end user is able to access the system securely through the internet on a standard web browser, thereby eliminating the need for standalone installations on all machines. PMID:28375759

Baobab Laboratory Information Management System: Development of an Open-Source Laboratory Information Management System for Biobanking.

PubMed

Bendou, Hocine; Sizani, Lunga; Reid, Tim; Swanepoel, Carmen; Ademuyiwa, Toluwaleke; Merino-Martinez, Roxana; Meuller, Heimo; Abayomi, Akin; Christoffels, Alan

2017-04-01

A laboratory information management system (LIMS) is central to the informatics infrastructure that underlies biobanking activities. To date, a wide range of commercial and open-source LIMSs are available and the decision to opt for one LIMS over another is often influenced by the needs of the biobank clients and researchers, as well as available financial resources. The Baobab LIMS was developed by customizing the Bika LIMS software ( www.bikalims.org ) to meet the requirements of biobanking best practices. The need to implement biobank standard operation procedures as well as stimulate the use of standards for biobank data representation motivated the implementation of Baobab LIMS, an open-source LIMS for Biobanking. Baobab LIMS comprises modules for biospecimen kit assembly, shipping of biospecimen kits, storage management, analysis requests, reporting, and invoicing. The Baobab LIMS is based on the Plone web-content management framework. All the system requirements for Plone are applicable to Baobab LIMS, including the need for a server with at least 8 GB RAM and 120 GB hard disk space. Baobab LIMS is a server-client-based system, whereby the end user is able to access the system securely through the internet on a standard web browser, thereby eliminating the need for standalone installations on all machines.

Thyroid Cancer and Tumor Collaborative Registry (TCCR).

PubMed

Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B; Sherman, Simon

2016-01-01

A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC.

Rationale and study design of the Japan environment and children's study (JECS).

PubMed

Kawamoto, Toshihiro; Nitta, Hiroshi; Murata, Katsuyuki; Toda, Eisaku; Tsukamoto, Naoya; Hasegawa, Manabu; Yamagata, Zentaro; Kayama, Fujio; Kishi, Reiko; Ohya, Yukihiro; Saito, Hirohisa; Sago, Haruhiko; Okuyama, Makiko; Ogata, Tsutomu; Yokoya, Susumu; Koresawa, Yuji; Shibata, Yasuyuki; Nakayama, Shoji; Michikawa, Takehiro; Takeuchi, Ayano; Satoh, Hiroshi

2014-01-10

There is global concern over significant threats from a wide variety of environmental hazards to which children face. Large-scale and long-term birth cohort studies are needed for better environmental management based on sound science. The primary objective of the Japan Environment and Children's Study (JECS), a nation-wide birth cohort study that started its recruitment in January 2011, is to elucidate environmental factors that affect children's health and development. Approximately 100,000 expecting mothers who live in designated study areas will be recruited over a 3-year period from January 2011. Participating children will be followed until they reach 13 years of age. Exposure to environmental factors will be assessed by chemical analyses of bio-specimens (blood, cord blood, urine, breast milk, and hair), household environment measurements, and computational simulations using monitoring data (e.g. ambient air quality monitoring) as well as questionnaires. JECS' priority outcomes include reproduction/pregnancy complications, congenital anomalies, neuropsychiatric disorders, immune system disorders, and metabolic/endocrine system disorders. Genetic factors, socioeconomic status, and lifestyle factors will also be examined as covariates and potential confounders. To maximize representativeness, we adopted provider-mediated community-based recruitment. Through JECS, chemical substances to which children are exposed during the fetal stage or early childhood will be identified. The JECS results will be translated to better risk assessment and management to provide healthy environment for next generations.

Distant testing in laboratory hematology and flow cytometry--the Indian experience.

PubMed

Das Gupta, Amar

2012-06-01

Outsourcing or sending out of patients' samples to other laboratories for hematologic investigations is a common practice these days. Preanalytic variables that alter cellular parameters and levels of analytes in transit and on storage can significantly and adversely affect interpretation of test results in hematology. Awareness of these changes is necessary to avoid misinterpretation of results that in turn could influence medical management decisions.

Preanalytic process linked to spuriously elevated HIV viral loads: improvement on an FDA-approved process.

PubMed

Procop, Gary W; Taege, Alan J; Starkey, Colleen; Tungsiripat, Marisa; Warner, Diane; Schold, Jesse D; Yen-Lieberman, Belinda

2017-09-01

The processing of specimens often occurs in a central processing area within laboratories. We demonstrated that plasma centrifuged in the central laboratory but allowed to remain within the primary tube following centrifugation was associated with spuriously elevated HIV viral loads compared with recentrifugation of the plasma just prior to testing. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative Assessment of Effect of Preanalytic Cold Ischemic Time on Protein Expression in Breast Cancer Tissues

PubMed Central

2012-01-01

Background Companion diagnostic tests can depend on accurate measurement of protein expression in tissues. Preanalytic variables, especially cold ischemic time (time from tissue removal to fixation in formalin) can affect the measurement and may cause false-negative results. We examined 23 proteins, including four commonly used breast cancer biomarker proteins, to quantify their sensitivity to cold ischemia in breast cancer tissues. Methods A series of 93 breast cancer specimens with known time-to-fixation represented in a tissue microarray and a second series of 25 matched pairs of core needle biopsies and breast cancer resections were used to evaluate changes in antigenicity as a function of cold ischemic time. Estrogen receptor (ER), progesterone receptor (PgR), HER2 or Ki67, and 19 other antigens were tested. Each antigen was measured using the AQUA method of quantitative immunofluorescence on at least one series. All statistical tests were two-sided. Results We found no evidence for loss of antigenicity with time-to-fixation for ER, PgR, HER2, or Ki67 in a 4-hour time window. However, with a bootstrapping analysis, we observed a trend toward loss for ER and PgR, a statistically significant loss of antigenicity for phosphorylated tyrosine (P = .0048), and trends toward loss for other proteins. There was evidence of increased antigenicity in acetylated lysine, AKAP13 (P = .009), and HIF1A (P = .046), which are proteins known to be expressed in conditions of hypoxia. The loss of antigenicity for phosphorylated tyrosine and increase in expression of AKAP13, and HIF1A were confirmed in the biopsy/resection series. Conclusions Key breast cancer biomarkers show no evidence of loss of antigenicity, although this dataset assesses the relatively short time beyond the 1-hour limit in recent guidelines. Other proteins show changes in antigenicity in both directions. Future studies that extend the time range and normalize for heterogeneity will provide more comprehensive information on preanalytic variation due to cold ischemic time. PMID:23090068

Background | Office of Cancer Clinical Proteomics Research

Cancer.gov

The term "proteomics" refers to a large-scale comprehensive study of a specific proteome resulting from its genome, including abundances of proteins, their variations and modifications, and interacting partners and networks in order to understand cellular processes involved.  Similarly, “Cancer proteomics” refers to comprehensive analyses of proteins and their derivatives translated from a specific cancer genome using a human biospecimen or a preclinical model (e.g., cultured cell or animal model).

Protein C and protein S deficiencies: similarities and differences between two brothers playing in the same game.

PubMed

Bereczky, Zsuzsanna; Kovács, Kitti B; Muszbek, László

2010-12-01

Protein C (PC) and protein S (PS) are vitamin K-dependent glycoproteins that play an important role in the regulation of blood coagulation as natural anticoagulants. PC is activated by thrombin and the resulting activated PC (APC) inactivates membrane-bound activated factor VIII and factor V. The free form of PS is an important cofactor of APC. Deficiencies in these proteins lead to an increased risk of venous thromboembolism; a few reports have also associated these deficiencies with arterial diseases. The degree of risk and the prevalence of PC and PS deficiency among patients with thrombosis and in those in the general population have been examined by several population studies with conflicting results, primarily due to methodological variability. The molecular genetic background of PC and PS deficiencies is heterogeneous. Most of the mutations cause type I deficiency (quantitative disorder). Type II deficiency (dysfunctional molecule) is diagnosed in approximately 5%-15% of cases. The diagnosis of PC and PS deficiencies is challenging; functional tests are influenced by several pre-analytical and analytical factors, and the diagnosis using molecular genetics also has special difficulties. Large gene segment deletions often remain undetected by DNA sequencing methods. The presence of the PS pseudogene makes genetic diagnosis even more complicated.

Differences in metabolite profiles caused by pre-analytical blood processing procedures.

PubMed

Nishiumi, Shin; Suzuki, Makoto; Kobayashi, Takashi; Yoshida, Masaru

2018-05-01

Recently, the use of metabolomic analysis of human serum and plasma for biomarker discovery and disease diagnosis in clinical studies has been increasing. The feasibility of using a metabolite biomarker for disease diagnosis is strongly dependent on the metabolite's stability during pre-analytical blood processing procedures, such as serum or plasma sampling and sample storage prior to centrifugation. However, the influence of blood processing procedures on the stability of metabolites has not been fully characterized. In the present study, we compared the levels of metabolites in matched human serum and plasma samples using gas chromatography coupled with mass spectrometry and liquid chromatography coupled with mass spectrometry. In addition, we evaluated the changes in plasma metabolite levels induced by storage at room temperature or at a cold temperature prior to centrifugation. As a result, it was found that 76 metabolites exhibited significant differences between their serum and plasma levels. Furthermore, the pre-centrifugation storage conditions significantly affected the plasma levels of 45 metabolites. These results highlight the importance of blood processing procedures during metabolome analysis, which should be considered during biomarker discovery and the subsequent use of biomarkers for disease diagnosis. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Investigations of blood ammonia analysis: Test matrices, storage, and stability.

PubMed

Goldstein, Brittany N; Wesler, Jordan; Nowacki, Amy S; Reineks, Edmunds; Natowicz, Marvin R

2017-06-01

An assessment of blood ammonia concentration is common medical practice in the evaluation of an individual with an unexplained mental status change or coma. The determination of a blood ammonia level is most commonly done using a glutamate dehydrogenase (GLDH)-based assay, although there are many potential sources of artifact and the literature is inconsistent regarding key preanalytic issues. Using a GLDH-based assay, we first investigated matrix effects using three anticoagulants: heparin, EDTA and oxalate. Heparin-anticoagulated plasma was substantially less precise than EDTA- and oxalate-anticoagulated plasma. Oxalate-anticoagulated plasma showed a greater baseline of apparent ammonia than either heparin- or EDTA-derived plasma, presumably due to interferants. We then evaluated the stability of EDTA-anticoagulated plasma for assessment of ammonia when stored at 4°C,-14°C or -70°C. There was a linear increase of ammonia with storage at both 4°C and -14°C. Plasma kept at -70°C for up to three weeks showed no change in measured ammonia relative to the baseline determination. This work clarifies preanalytic conditions for which a precise determination of ammonia can be accomplished using a GLDH-based assay. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Tissue is alive: New technologies are needed to address the problems of protein biomarker pre-analytical variability.

PubMed

Espina, Virginia; Mueller, Claudius; Edmiston, Kirsten; Sciro, Manuela; Petricoin, Emanuel F; Liotta, Lance A

2009-08-01

Instability of tissue protein biomarkers is a critical issue for molecular profiling. Pre-analytical variables during tissue procurement, such as time delays during which the tissue remains stored at room temperature, can cause significant variability and bias in downstream molecular analysis. Living tissue, ex vivo, goes through a defined stage of reactive changes that begin with oxidative, hypoxic and metabolic stress, and culminate in apoptosis. Depending on the delay time ex vivo, and reactive stage, protein biomarkers, such as signal pathway phosphoproteins will be elevated or suppressed in a manner which does not represent the biomarker levels at the time of excision. Proteomic data documenting reactive tissue protein changes post collection indicate the need to recognize and address tissue stability, preservation of post-translational modifications, and preservation of morphologic features for molecular analysis. Based on the analysis of phosphoproteins, one of the most labile tissue protein biomarkers, we set forth tissue procurement guidelines for clinical research. We propose technical solutions for (i) assessing the state of protein analyte preservation and specimen quality via identification of a panel of natural proteins (surrogate stability markers), and (ii) using multi-purpose fixative solution designed to stabilize, preserve and maintain proteins, nucleic acids, and tissue architecture.

Tissue is alive: New technologies are needed to address the problems of protein biomarker pre-analytical variability

PubMed Central

Espina, Virginia; Mueller, Claudius; Edmiston, Kirsten; Sciro, Manuela; Petricoin, Emanuel F.; Liotta, Lance A.

2010-01-01

Instability of tissue protein biomarkers is a critical issue for molecular profiling. Pre-analytical variables during tissue procurement, such as time delays during which the tissue remains stored at room temperature, can cause significant variability and bias in downstream molecular analysis. Living tissue, ex vivo, goes through a defined stage of reactive changes that begin with oxidative, hypoxic and metabolic stress, and culminate in apoptosis. Depending on the delay time ex vivo, and reactive stage, protein biomarkers, such as signal pathway phosphoproteins will be elevated or suppressed in a manner which does not represent the biomarker levels at the time of excision. Proteomic data documenting reactive tissue protein changes post collection indicate the need to recognize and address tissue stability, preservation of post-translational modifications, and preservation of morphologic features for molecular analysis. Based on the analysis of phosphoproteins, one of the most labile tissue protein biomarkers, we set forth tissue procurement guidelines for clinical research. We propose technical solutions for (i) assessing the state of protein analyte preservation and specimen quality via identification of a panel of natural proteins (surrogate stability markers), and (ii) using multi-purpose fixative solution designed to stabilize, preserve and maintain proteins, nucleic acids, and tissue architecture. PMID:20871745

Laboratory Automation and Intra-Laboratory Turnaround Time: Experience at the University Hospital Campus Bio-Medico of Rome.

PubMed

Angeletti, Silvia; De Cesaris, Marina; Hart, Jonathan George; Urbano, Michele; Vitali, Massimiliano Andrea; Fragliasso, Fulvio; Dicuonzo, Giordano

2015-12-01

Intra-laboratory turnaround time (TAT) is a key indicator of laboratory performance. Improving TAT is a complex task requiring staff education, equipment acquisition, and adequate TAT monitoring. The aim of the present study was to evaluate the intra-laboratory TAT after laboratory automation implementation (June 2013-June 2014) and to compare it to that in the preautomation period (July 2012-May 2013). Intra-laboratory TAT was evaluated both as the mean TAT registered and the percentage of outlier (OP) exams. The mean TAT was 36, 38, and 34 min during the study periods, respectively. These values respected the goal TAT established at 45 min. The OP, calculated at 45 min as well as at 60 min, decreased from 26 to 21 and from 11 to 5, respectively. From a focused analysis on blood count cell, troponin I, and prothrombin (PT) test, TAT improvement was more evident for tests requiring longer preanalytical process. The follow-up of TAT from June 2013 to June 2014 revealed the reduction of the mean TAT as well as of the OP exams after automation implementation and that automation more strongly affects the test in the preanalytical phase including centrifugation of the sample, such as troponin I and PT. © 2015 Society for Laboratory Automation and Screening.

The Biomarker Knowledge System Informatics Pilot Project Supplement To The Biomarker Development Laboratory at Moffitt (Bedlam) — EDRN Public Portal

Cancer.gov

The Biomarker Knowledge System Informatics Pilot Project goal will develop network interfaces among databases that contain information about existing clinical populations and biospecimens and data relating to those specimens that are important in biomarker assay validation. This protocol comprises one of two that will comprise the Moffitt participation in the Biomarker Knowledge System Informatics Pilot Project. THIS PROTOCOL (58) is the Sput-Epi Database.

Is Your Biobank Up to Standards? A Review of the National Canadian Tissue Repository Network Required Operational Practice Standards and the Controlled Documents of a Certified Biobank.

PubMed

Hartman, Victoria; Castillo-Pelayo, Tania; Babinszky, Sindy; Dee, Simon; Leblanc, Jodi; Matzke, Lise; O'Donoghue, Sheila; Carpenter, Jane; Carter, Candace; Rush, Amanda; Byrne, Jennifer; Barnes, Rebecca; Mes-Messons, Anne-Marie; Watson, Peter

2018-02-01

Ongoing quality management is an essential part of biobank operations and the creation of high quality biospecimen resources. Adhering to the standards of a national biobanking network is a way to reduce variability between individual biobank processes, resulting in cross biobank compatibility and more consistent support for health researchers. The Canadian Tissue Repository Network (CTRNet) implemented a set of required operational practices (ROPs) in 2011 and these serve as the standards and basis for the CTRNet biobank certification program. A review of these 13 ROPs covering 314 directives was conducted after 5 years to identify areas for revision and update, leading to changes to 7/314 directives (2.3%). A review of all internal controlled documents (including policies, standard operating procedures and guides, and forms for actions and processes) used by the BC Cancer Agency's Tumor Tissue Repository (BCCA-TTR) to conform to these ROPs was then conducted. Changes were made to 20/106 (19%) of BCCA-TTR documents. We conclude that a substantial fraction of internal controlled documents require updates at regular intervals to accommodate changes in best practices. Reviewing documentation is an essential aspect of keeping up to date with best practices and ensuring the quality of biospecimens and data managed by biobanks.

Infrastructure resources for clinical research in amyotrophic lateral sclerosis.

PubMed

Sherman, Alexander V; Gubitz, Amelie K; Al-Chalabi, Ammar; Bedlack, Richard; Berry, James; Conwit, Robin; Harris, Brent T; Horton, D Kevin; Kaufmann, Petra; Leitner, Melanie L; Miller, Robert; Shefner, Jeremy; Vonsattel, Jean Paul; Mitsumoto, Hiroshi

2013-05-01

Clinical trial networks, shared clinical databases, and human biospecimen repositories are examples of infrastructure resources aimed at enhancing and expediting clinical and/or patient oriented research to uncover the etiology and pathogenesis of amyotrophic lateral sclerosis (ALS), a rapidly progressive neurodegenerative disease that leads to the paralysis of voluntary muscles. The current status of such infrastructure resources, as well as opportunities and impediments, were discussed at the second Tarrytown ALS meeting held in September 2011. The discussion focused on resources developed and maintained by ALS clinics and centers in North America and Europe, various clinical trial networks, U.S. government federal agencies including the National Institutes of Health (NIH), the Agency for Toxic Substances and Disease Registry (ATSDR) and the Centers for Disease Control and Prevention (CDC), and several voluntary disease organizations that support ALS research activities. Key recommendations included 1) the establishment of shared databases among individual ALS clinics to enhance the coordination of resources and data analyses; 2) the expansion of quality-controlled human biospecimen banks; and 3) the adoption of uniform data standards, such as the recently developed Common Data Elements (CDEs) for ALS clinical research. The value of clinical trial networks such as the Northeast ALS (NEALS) Consortium and the Western ALS (WALS) Consortium was recognized, and strategies to further enhance and complement these networks and their research resources were discussed.

Fundamental Considerations for Biobank Legacy Planning

PubMed Central

Fombonne, Benjamin; Watson, Peter Hamilton; Moore, Helen Marie

2016-01-01

Biobanking in its various forms is an activity involving the collection of biospecimens and associated data and their storage for differing lengths of time before use. In some cases, biospecimens are immediately used, but in others, they are stored typically for the term of a specified project or in perpetuity until the materials are used up or declared to be of little scientific value. Legacy planning involves preparing for the phase that follows either biobank closure or a significant change at an operational level. In the case of a classical finite collection, this may be brought about by the completion of the initial scientific goals of a project, a loss of funding, or loss of or change in leadership. Ultimately, this may require making a decision about when and where to transfer materials or whether to destroy them. Because biobanking in its entirety is a complex endeavour, legacy planning touches on biobank operations as well as ethical, legal, financial, and governance parameters. Given the expense and time that goes into setting up and maintaining biobanks, coupled with the ethical imperative to appropriately utilize precious resources donated to research, legacy planning is an activity that every biobanking entity should think about. This article describes some of the fundamental considerations for preparing and executing a legacy plan, and we envisage that this article will facilitate dialogue to help inform best practices and policy development in the future. PMID:26890981

Thyroid Cancer and Tumor Collaborative Registry (TCCR)

PubMed Central

Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B.; Sherman, Simon

2016-01-01

A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC. PMID:27168721

Views on clinical trial recruitment, biospecimen collection, and cancer research: population science from landscapes of the Haudenosaunee (People of the Longhouse).

PubMed

Haring, Rodney C; Henry, Whitney Ann; Hudson, Maui; Rodriguez, Elisa M; Taualii, Maile

2018-02-01

Biomedical research in culturally distinct communities is often a challenge. Potential barriers to participation occur because science is presented in a format that lacks cultural acknowledgement. Investigations may also fail to showcase beneficial relevance to the communities or include them in true partnership. The history of biomedical research within Native American societies has been complicated by these issues. Historical trauma among many Native groups sometimes transcends into contemporary challenges in both recruitment to and participation particularly in biobanking research. The participants for this study included members of the Haudenosaunee, the People of the Longhouse. Native Americans, including the Haudenosaunee, endure some of the worst health disparities in the country. These include high rates of cancer, obesity, and diabetes which may be linked at least partially to genetic predisposition. Results from a Haudenosaunee urban population shared response on ways to improve recruitment strategies for biospecimen, cancer, and other health-related clinical trials. Mixed methods approaches were used, and community responses indicated the importance of creating trust through respectful partnership; promoting culturally appropriate recruitment materials; the need for a greater understanding of consenting and signature processes; the necessity for concise summary sheets; and a desire to have information that community member understand. Discussion items also include international Indigenous perspectives to biobanking and genetic-related health disparity research.

An Efficient Design Strategy for Logistic Regression Using Outcome- and Covariate-Dependent Pooling of Biospecimens Prior to Assay

PubMed Central

Lyles, Robert H.; Mitchell, Emily M.; Weinberg, Clarice R.; Umbach, David M.; Schisterman, Enrique F.

2016-01-01

Summary Potential reductions in laboratory assay costs afforded by pooling equal aliquots of biospecimens have long been recognized in disease surveillance and epidemiological research and, more recently, have motivated design and analytic developments in regression settings. For example, Weinberg and Umbach (1999, Biometrics 55, 718–726) provided methods for fitting set-based logistic regression models to case-control data when a continuous exposure variable (e.g., a biomarker) is assayed on pooled specimens. We focus on improving estimation efficiency by utilizing available subject-specific information at the pool allocation stage. We find that a strategy that we call “(y,c)-pooling,” which forms pooling sets of individuals within strata defined jointly by the outcome and other covariates, provides more precise estimation of the risk parameters associated with those covariates than does pooling within strata defined only by the outcome. We review the approach to set-based analysis through offsets developed by Weinberg and Umbach in a recent correction to their original paper. We propose a method for variance estimation under this design and use simulations and a real-data example to illustrate the precision benefits of (y,c)-pooling relative to y-pooling. We also note and illustrate that set-based models permit estimation of covariate interactions with exposure. PMID:26964741

A National Virtual Specimen Database for Early Cancer Detection

NASA Technical Reports Server (NTRS)

Crichton, Daniel; Kincaid, Heather; Kelly, Sean; Thornquist, Mark; Johnsey, Donald; Winget, Marcy

2003-01-01

Access to biospecimens is essential for enabling cancer biomarker discovery. The National Cancer Institute's (NCI) Early Detection Research Network (EDRN) comprises and integrates a large number of laboratories into a network in order to establish a collaborative scientific environment to discover and validate disease markers. The diversity of both the institutions and the collaborative focus has created the need for establishing cross-disciplinary teams focused on integrating expertise in biomedical research, computational and biostatistics, and computer science. Given the collaborative design of the network, the EDRN needed an informatics infrastructure. The Fred Hutchinson Cancer Research Center, the National Cancer Institute,and NASA's Jet Propulsion Laboratory (JPL) teamed up to build an informatics infrastructure creating a collaborative, science-driven research environment despite the geographic and morphology differences of the information systems that existed within the diverse network. EDRN investigators identified the need to share biospecimen data captured across the country managed in disparate databases. As a result, the informatics team initiated an effort to create a virtual tissue database whereby scientists could search and locate details about specimens located at collaborating laboratories. Each database, however, was locally implemented and integrated into collection processes and methods unique to each institution. This meant that efforts to integrate databases needed to be done in a manner that did not require redesign or re-implementation of existing system

Clinical genomics, big data, and electronic medical records: reconciling patient rights with research when privacy and science collide.

PubMed

Kulynych, Jennifer; Greely, Henry T

2017-04-01

Widespread use of medical records for research, without consent, attracts little scrutiny compared to biospecimen research, where concerns about genomic privacy prompted recent federal proposals to mandate consent. This paper explores an important consequence of the proliferation of electronic health records (EHRs) in this permissive atmosphere: with the advent of clinical gene sequencing, EHR-based secondary research poses genetic privacy risks akin to those of biospecimen research, yet regulators still permit researchers to call gene sequence data 'de-identified', removing such data from the protection of the federal Privacy Rule and federal human subjects regulations. Medical centers and other providers seeking to offer genomic 'personalized medicine' now confront the problem of governing the secondary use of clinical genomic data as privacy risks escalate. We argue that regulators should no longer permit HIPAA-covered entities to treat dense genomic data as de-identified health information. Even with this step, the Privacy Rule would still permit disclosure of clinical genomic data for research, without consent, under a data use agreement, so we also urge that providers give patients specific notice before disclosing clinical genomic data for research, permitting (where possible) some degree of choice and control. To aid providers who offer clinical gene sequencing, we suggest both general approaches and specific actions to reconcile patients' rights and interests with genomic research.

Fee-For-Service as a Business Model of Growing Importance: The Academic Biobank Experience

PubMed Central

Sommerkamp, Kara; Egan-Palmer, Maureen; Kharasch, Karen; Holtschlag, Victoria

2012-01-01

Biorepositories offer tremendous scientific value to a wide variety of customer groups (academic, commercial, industrial) in their ability to deliver a centralized, standardized service model, encompassing both biospecimen storage and related laboratory services. Generally, the scientific expertise and economies of scale that are offered in centralized, properly resourced research biobanks has yielded value that has been well-recognized by universities, pharmaceutical companies, and other sponsoring institutions. However, like many facets of the economy, biobanks have been under increasing cost pressure in recent years. This has been a particular problem in the academic arena, where direct support from grant sources (both governmental and philanthropic) typically now is more difficult to secure, or provides reduced financial support, relative to previous years. One way to address this challenge is to establish or enhance a well-defined fee-for-service model which is properly calibrated to cover operational costs while still offering competitive value to users. In this model, customers are never charged for the biospecimens themselves, but rather for the laboratory services associated with them. Good communication practices, proper assessment of value, implementation of best practices, and a sound business plan are all needed for this initiative to succeed. Here we summarize our experiences at Washington University School of Medicine in the expectation they will be useful to others. PMID:23386922

Clinical genomics, big data, and electronic medical records: reconciling patient rights with research when privacy and science collide

PubMed Central

Greely, Henry T.

2017-01-01

Abstract Widespread use of medical records for research, without consent, attracts little scrutiny compared to biospecimen research, where concerns about genomic privacy prompted recent federal proposals to mandate consent. This paper explores an important consequence of the proliferation of electronic health records (EHRs) in this permissive atmosphere: with the advent of clinical gene sequencing, EHR-based secondary research poses genetic privacy risks akin to those of biospecimen research, yet regulators still permit researchers to call gene sequence data ‘de-identified’, removing such data from the protection of the federal Privacy Rule and federal human subjects regulations. Medical centers and other providers seeking to offer genomic ‘personalized medicine’ now confront the problem of governing the secondary use of clinical genomic data as privacy risks escalate. We argue that regulators should no longer permit HIPAA-covered entities to treat dense genomic data as de-identified health information. Even with this step, the Privacy Rule would still permit disclosure of clinical genomic data for research, without consent, under a data use agreement, so we also urge that providers give patients specific notice before disclosing clinical genomic data for research, permitting (where possible) some degree of choice and control. To aid providers who offer clinical gene sequencing, we suggest both general approaches and specific actions to reconcile patients’ rights and interests with genomic research. PMID:28852559

Targeted Selected Reaction Monitoring Mass Spectrometric Immunoassay for Insulin-like Growth Factor 1

PubMed Central

Niederkofler, Eric E.; Phillips, David A.; Krastins, Bryan; Kulasingam, Vathany; Kiernan, Urban A.; Tubbs, Kemmons A.; Peterman, Scott M.; Prakash, Amol; Diamandis, Eleftherios P.; Lopez, Mary F.; Nedelkov, Dobrin

2013-01-01

Insulin-like growth factor 1 (IGF1) is an important biomarker of human growth disorders that is routinely analyzed in clinical laboratories. Mass spectrometry-based workflows offer a viable alternative to standard IGF1 immunoassays, which utilize various pre-analytical preparation strategies. In this work we developed an assay that incorporates a novel sample preparation method for dissociating IGF1 from its binding proteins. The workflow also includes an immunoaffinity step using antibody-derivatized pipette tips, followed by elution, trypsin digestion, and LC-MS/MS separation and detection of the signature peptides in a selected reaction monitoring (SRM) mode. The resulting quantitative mass spectrometric immunoassay (MSIA) exhibited good linearity in the range of 1 to 1,500 ng/mL IGF1, intra- and inter-assay precision with CVs of less than 10%, and lowest limits of detection of 1 ng/mL. The linearity and recovery characteristics of the assay were also established, and the new method compared to a commercially available immunoassay using a large cohort of human serum samples. The IGF1 SRM MSIA is well suited for use in clinical laboratories. PMID:24278387

Evidence-based best practices for EGFR T790M testing in lung cancer in Canada.

PubMed

Stockley, T; Souza, C A; Cheema, P K; Melosky, B; Kamel-Reid, S; Tsao, M S; Spatz, A; Karsan, A

2018-04-01

Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are recommended as first-line systemic therapy for patients with non-small-cell lung cancer (nsclc) having mutations in the EGFR gene. Resistance to tkis eventually occurs in all nsclc patients treated with such drugs. In patients with resistance to tkis caused by the EGFR T790M mutation, the third-generation tki osimertinib is now the standard of care. For optimal patient management, accurate EGFR T790M testing is required. A multidisciplinary working group of pathologists, laboratory medicine specialists, medical oncologists, a respirologist, and a thoracic radiologist from across Canada was convened to discuss best practices for EGFR T790M mutation testing in Canada. The group made recommendations in the areas of the testing algorithm and the pre-analytic, analytic, and post-analytic aspects of clinical testing for both tissue testing and liquid biopsy circulating tumour dna testing. The recommendations aim to improve EGFR T790M testing in Canada and to thereby improve patient care.

Exposure Measurements in Japan Environment and Children's Study.

PubMed

Nakayama, Shoji

2016-01-01

The Japan Ministry of the Environment is conducting a large-scale birth cohort study called the Japan Environment and Children's Study (JECS), which involves 100000 mother-child pairs. Mothers are enrolled during pregnancy, and their children are followed up and studied until they reach the age of 13 years. The JECS started recruiting mothers in January 2011 and completed the registration of more than 103000 mothers in March 2014. The National Institute for Environmental Studies takes the lead in the study programming and implementation in cooperation with the National Centre for Child Health and Development and 15 Regional Centres that reach out to the study participants. In the study, the effects of environmental factors on children's health and development are investigated. The environment in this study is defined not only as air, soil, water, and indoor environments but also as various chemical substances, physical conditions, socioeconomic factors, psychological conditions, lifestyles and community situations. Mothers' and children's exposures to these environmental factors are measured through chemical analyses of biospecimens collected during pregnancy and after birth, questionnaires and computer modelling. The homes of the randomly selected participants (5000) are visited to measure the concentrations of volatile organic compounds, nitrogen and sulphuric oxides and particulate matter. Vacuum dust samples are also collected for chemical analysis. All these data will be combined with the information collected by the dwelling unit observation to assess the exposure of children aged 1.5 and 3 years.

Evaluation of the appropriate time period between sampling and analyzing for automated urinalysis

PubMed Central

Dolscheid-Pommerich, Ramona C.; Klarmann-Schulz, Ute; Conrad, Rupert; Stoffel-Wagner, Birgit; Zur, Berndt

2016-01-01

Introduction Preanalytical specifications for urinalysis must be strictly adhered to avoid false interpretations. Aim of the present study is to examine whether the preanalytical factor ‘time point of analysis’ significantly influences stability of urine samples for urine particle and dipstick analysis. Materials and methods In 321 pathological spontaneous urine samples, urine dipstick (Urisys™2400, Combur-10-Test™strips, Roche Diagnostics, Mannheim, Germany) and particle analysis (UF-1000 i™, Sysmex, Norderstedt, Germany) were performed within 90 min, 120 min and 240 min after urine collection. Results For urine particle analysis, a significant increase in conductivity (120 vs. 90 min: P < 0.001, 240 vs. 90 min: P < 0.001) and a significant decrease in WBC (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), RBC (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), casts (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001) and epithelial cells (120 vs. 90 min P = 0.610, 240 vs. 90 min P = 0.041) were found. There were no significant changes for bacteria. Regarding urine dipstick analysis, misclassification rates between measurements were significant for pH (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), leukocytes (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), nitrite (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), protein (120 vs. 90 min P < 0.001, 240 vs. 90 min P<0.001), ketone (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), blood (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), specific gravity (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001) and urobilinogen (120 vs. 90 min, P = 0.031). Misclassification rates were not significant for glucose and bilirubin. Conclusion Most parameters critically depend on the time window between sampling and analysis. Our study stresses the importance of adherence to early time points in urinalysis (within 90 min). PMID:26981022

Preservation of Biospecimens at Ambient Temperature: Special Focus on Nucleic Acids and Opportunities for the Biobanking Community.

PubMed

Muller, Rolf; Betsou, Fay; Barnes, Michael G; Harding, Keith; Bonnet, Jacques; Kofanova, Olga; Crowe, John H

2016-04-01

Several approaches to the preservation of biological materials at ambient temperature and the relative impact on sample stability and degradation are reviewed, with a focus on nucleic acids. This appraisal is undertaken within the framework of biobank risk, quality management systems, and accreditation, with a view to assessing how best to apply ambient temperature sample storage to ensure stability, reduce costs, improve handling logistics, and increase the efficiency of biobank procedures.

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2013-10-01

Carcinoma Stage IIB N N .149 1 8 .132 1 8 .092 1 No - Quit Smoking 50 AR Agent Orange , Nuclear weapons, Second-hand smoke Agent Orange , Nuclear weapons...Smoking 30 None Agent Orange , Asbestos, Second-hand smoke Agent Orange , Asbestos, Second-hand smoke S0159 Squamous Cell Carcinoma Stage IIB Y N...2.560 100 80 25 6 7 0.670 4 4 0.370 1 No - Quit Smoking 30 NV Agent Orange , Asbestos, Nuclear weapons, Second- hand smoke Agent Orange , Asbestos

Comprehensive Reproductive System Care Program - Clinical Breast Care Project (CRSCP-CBCP)

DTIC Science & Technology

2013-04-01

tumor heterogeneity. The tumor microenvironment and stromal interactions, metastasis and recurrence, as well as the role of cancer stem cells and tumor...biospecimens (Figure BB-1) donated by 5,977 fully consented subjects to our IRB approved tissue and blood protocols. (Figure BB-2) 10 1/1 c Cll ...E ’(3 Cll c. 1/1 c;; 0 1- CBCP Total Biological Specimens, Cumulative Annual Total thru 3/31/13 60000 50000 40000 30000 20000 10000 0

The Image and Data Archive at the Laboratory of Neuro Imaging.

PubMed

Crawford, Karen L; Neu, Scott C; Toga, Arthur W

2016-01-01

The LONI Image and Data Archive (IDA)(1) is a repository for sharing and long-term preservation of neuroimaging and biomedical research data. Originally designed to archive strictly medical image files, the IDA has evolved over the last ten years and now encompasses the storage and dissemination of neuroimaging, clinical, biospecimen, and genetic data. In this article, we report upon the genesis of the IDA and how it currently securely manages data and protects data ownership. Copyright © 2015 Elsevier Inc. All rights reserved.

Tissue Preservation Assessment Preliminary Results

NASA Technical Reports Server (NTRS)

Globus, Ruth; Costes, Sylvain

2017-01-01

Pre-flight groundbased testing done to prepare for the first Rodent Research mission validation flight, RR1 (Choi et al, 2016 PlosOne). We purified RNA and measured RIN values to assess quality of the samples. For protein, we measured liver enzyme activities. We tested protocol and methods of preservation to date. Here we present an overview of results related to tissue preservation from the RR1 validation mission and a summary of findings to date from investigators who received RR1 teissues various Biospecimen Sharing Program.

Rationale and study design of the Japan environment and children’s study (JECS)

PubMed Central

2014-01-01

Background There is global concern over significant threats from a wide variety of environmental hazards to which children face. Large-scale and long-term birth cohort studies are needed for better environmental management based on sound science. The primary objective of the Japan Environment and Children’s Study (JECS), a nation-wide birth cohort study that started its recruitment in January 2011, is to elucidate environmental factors that affect children’s health and development. Methods/Design Approximately 100,000 expecting mothers who live in designated study areas will be recruited over a 3-year period from January 2011. Participating children will be followed until they reach 13 years of age. Exposure to environmental factors will be assessed by chemical analyses of bio-specimens (blood, cord blood, urine, breast milk, and hair), household environment measurements, and computational simulations using monitoring data (e.g. ambient air quality monitoring) as well as questionnaires. JECS’ priority outcomes include reproduction/pregnancy complications, congenital anomalies, neuropsychiatric disorders, immune system disorders, and metabolic/endocrine system disorders. Genetic factors, socioeconomic status, and lifestyle factors will also be examined as covariates and potential confounders. To maximize representativeness, we adopted provider-mediated community-based recruitment. Discussion Through JECS, chemical substances to which children are exposed during the fetal stage or early childhood will be identified. The JECS results will be translated to better risk assessment and management to provide healthy environment for next generations. PMID:24410977

Role of training activities for the reduction of pre-analytical errors in laboratory samples from primary care.

PubMed

Romero, Adolfo; Cobos, Andrés; Gómez, Juan; Muñoz, Manuel

2012-01-18

The presence of pre-analytical errors (PE) is a usual contingency in laboratories. The incidence may increase where it is difficult to control that period, as it is the case with samples sent from primary care (PC) to clinical reference laboratory. Detection of a large number of PE in PC samples in our Institution led to the development and implementation of preventive strategies. The first of these has been the realization of a cycle of educational sessions for PC nurses, followed by the evaluation of their impact on PE number. The incidence of PE was assessed in two periods, before (October-November 2007) and after (October-November, 2009) the implementation of educational sessions. Eleven PC centers in the urban area and 17 in the rural area participated. In the urban area, samples were withdrawn by any PC nurse; in the rural area, samples were obtained by the patient's reference nurse. The types of analyzed PE included missed sample (MS), hemolyzed sample (HS), coagulated sample (CS), incorrect sample (ISV) and others (OPE), such as lipemic or icteric serum or plasma. In the former period, we received 52,669 blood samples and 18,852 urine samples, detecting 3885 (7.5%) and 1567 (8.3%) PEs, respectively. After the educational intervention, there were 52,659 and 19,048 samples with 5057 (9.6%) and 1.256 (6.5%) PEs, respectively (p<0.001). According to the type of PE, the incidents compared before and after compared incidences were: MS, 4.8% vs. 3.8%, p<0.001; HS, 1.97% vs. 3.9%, p<0.001; CS, 0.54% vs. 0.25%, p<0.001; ISV, 0.15% vs. 0.19% p=0.08; and OPE, 0.3% vs. 0.42%, p<0.001. Surprisingly the PE incidence increased after the educational intervention, although it should be noted that it was primarily due to the increase of HS, as the other EP incidence decreased (MS and CS) or remained unchanged (ISV). This seems to indicate the need for a comprehensive approach to reduce the incidence of errors in the pre-analytical period, as one stage interventions do not seem to be effective enough. Copyright © 2011 Elsevier B.V. All rights reserved.

Technical performance of lactate biosensors and a test-strip device during labour.

PubMed

Luttkus, A K; Fotopoulou, C; Sehouli, J; Stupin, J; Dudenhausen, J W

2010-04-01

Lactate in fetal blood has a high diagnostic power to detect fetal compromise due to hypoxia, as lactate allows an estimation of duration and intensity of metabolic acidemia. Biosensor technology allows an instantaneous diagnosis of fetal compromise in the delivery room. The goal of the current investigation is to define the preanalytical and analytical biases of this technology under routine conditions in a labour ward in comparison to test-strip technology, which allows measurement of lactate alone. Three lactate biosensors (RapidLab 865, Siemens Medical Solutions Diagnostics, Bad Nauheim, Germany; Radiometer ABL625 and ABL 700, Radiometer Copenhagen, Denmark) and one test-strip device (Lactate Pro, Oxford Instruments, UK) were evaluated regarding precision in serial and repetitive measurements in over 1350 samples of fetal whole blood. The coefficient of variation (CV) and the standard deviation (SD) were calculated. The average value of all three biosensors was defined as an artificial reference value (refval). Blood tonometry was performed in order to test the quality of respiratory parameters and to simulate conditions of fetal hypoxia (pO (2): 10 and 20 mmHg). The precision of serial measurements of all biosensors indicated a coefficient of variation (CV) between 1.55 and 3.16% with an SD from 0.042 to 0.053 mmol/L. The test-strip device (Lactate Pro) mounted to 0.117 mmol/L and 3.99% (SD, CV). When compared to our reference value (refval) ABL 625 showed the closest correlation of -0.1%, while Siemens RapidLab 865 showed an overestimation of +8.9%, ABL700 an underestimation of -6.2% and Lactate Pro of -3.7%. For routine use all tested biosensors show sufficient precision. The test-strip device shows a slightly higher standard deviation. A direct comparison of measured lactate values from the various devices needs to be interpreted with caution as each method detects different lactate concentrations. Furthermore, the 40 min process of tonometry led to an increase of SD and coefficient of variation in all devices. This results in the important preanalytical finding that the precision of replicated measurements worsens significantly with time. The clinician should be aware of the type of analyser used and of preanalytical biases before making clinical decisions on the basis of lactate values.

Increased instrument intelligence--can it reduce laboratory error?

PubMed

Jekelis, Albert W

2005-01-01

Recent literature has focused on the reduction of laboratory errors and the potential impact on patient management. This study assessed the intelligent, automated preanalytical process-control abilities in newer generation analyzers as compared with older analyzers and the impact on error reduction. Three generations of immuno-chemistry analyzers were challenged with pooled human serum samples for a 3-week period. One of the three analyzers had an intelligent process of fluidics checks, including bubble detection. Bubbles can cause erroneous results due to incomplete sample aspiration. This variable was chosen because it is the most easily controlled sample defect that can be introduced. Traditionally, lab technicians have had to visually inspect each sample for the presence of bubbles. This is time consuming and introduces the possibility of human error. Instruments with bubble detection may be able to eliminate the human factor and reduce errors associated with the presence of bubbles. Specific samples were vortexed daily to introduce a visible quantity of bubbles, then immediately placed in the daily run. Errors were defined as a reported result greater than three standard deviations below the mean and associated with incomplete sample aspiration of the analyte of the individual analyzer Three standard deviations represented the target limits of proficiency testing. The results of the assays were examined for accuracy and precision. Efficiency, measured as process throughput, was also measured to associate a cost factor and potential impact of the error detection on the overall process. The analyzer performance stratified according to their level of internal process control The older analyzers without bubble detection reported 23 erred results. The newest analyzer with bubble detection reported one specimen incorrectly. The precision and accuracy of the nonvortexed specimens were excellent and acceptable for all three analyzers. No errors were found in the nonvortexed specimens. There were no significant differences in overall process time for any of the analyzers when tests were arranged in an optimal configuration. The analyzer with advanced fluidic intelligence demostrated the greatest ability to appropriately deal with an incomplete aspiration by not processing and reporting a result for the sample. This study suggests that preanalytical process-control capabilities could reduce errors. By association, it implies that similar intelligent process controls could favorably impact the error rate and, in the case of this instrument, do it without negatively impacting process throughput. Other improvements may be realized as a result of having an intelligent error-detection process including further reduction in misreported results, fewer repeats, less operator intervention, and less reagent waste.

Chlamydia trachomatis infection among 15- to 35-year-olds in Baltimore, MD.

PubMed

Eggleston, Elizabeth; Rogers, Susan M; Turner, Charles F; Miller, William C; Roman, Anthony M; Hobbs, Marcia M; Erbelding, Emily; Tan, Sylvia; Villarroel, Maria A; Ganapathi, Laxminarayana

2011-08-01

Chlamydia trachomatis (Ct) is the most frequently reported infectious disease in the United States. This article reports population and subpopulation prevalence estimates of Ct and correlates of infection among 15- to 35-year-olds in Baltimore, MD. The Monitoring STIs Survey Program (MSSP) monitored sexually transmitted infection (STI) prevalence among probability samples of residents of Baltimore, a city with high STI rates. MSSP respondents completed telephone audio computer-assisted self-interviews and provided biospecimens for STI testing. Among 2120 Baltimore residents aged 15 to 35 years, the estimated prevalence of chlamydia was 3.9% (95% confidence interval [CI]: 2.8, 5.0). Prevalence was 5.8% (95% CI: 4.1, 7.6) among black MSSP respondents versus 0.7% (95% CI: 0.0, 1.4) among nonblack respondents; all but 4 infections detected were among black respondents. Sexual behaviors and other factors associated with infection were far more prevalent among black than nonblack Baltimore residents. Racial disparities persisted after adjustment for sociodemographic, behavioral, and health factors. The MSSP highlights a higher Ct prevalence among young people in Baltimore than in the United States overall, with notable racial disparities in infection and associated risk behaviors. Public health efforts are needed to improve the diagnosis and treatment of asymptomatic infections in this population.

Chlamydia trachomatis infection among 15-35 year-olds in Baltimore, MD, USA

PubMed Central

Eggleston, Elizabeth; Rogers, Susan M; Turner, Charles F; Miller, William C.; Roman, Anthony M; Hobbs, Marcia M.; Erbelding, Emily; Tan, Sylvia; Villarroel, Maria A.; Ganapathi, Laxminarayana

2011-01-01

Background Chlamydia trachomatis (Ct) is the most frequently reported infectious disease in the U.S. This article reports population and subpopulation prevalence estimates of Ct and correlates of infection among 15-35 year-olds in Baltimore, MD, USA. Methods The Monitoring STIs Survey Program (MSSP) monitored STI prevalence among probability samples of residents of Baltimore, a city with high STI rates. MSSP respondents completed telephone audio computer-assisted self-interviews and provided biospecimens for STI testing. Results Among 2120 Baltimore residents aged 15 to 35 years, the estimated prevalence of chlamydia was 3.9% (95% Cl: 2.8, 5.0). Prevalence was 5.8% (95% Cl: 4.1, 7.6) among black MSSP respondents versus 0.7% (95% Cl: 0.0, 1.4) among nonblack respondents; all but four infections detected were among black respondents. Sexual behaviors and other factors associated with infection were far more prevalent among black than nonblack Baltimore residents. Racial disparities persisted after adjustment for sociodemographic, behavioral and health factors. Conclusion The MSSP highlights a higher Ct prevalence among young people in Baltimore than in the U.S. overall, with notable racial disparities in infection and associated risk behaviors. Public health efforts are needed to improve the diagnosis and treatment of asymptomatic infections in this population. PMID:21844726

Quality assurance in the pre-analytical phase of human urine samples by (1)H NMR spectroscopy.

PubMed

Budde, Kathrin; Gök, Ömer-Necmi; Pietzner, Maik; Meisinger, Christine; Leitzmann, Michael; Nauck, Matthias; Köttgen, Anna; Friedrich, Nele

2016-01-01

Metabolomic approaches investigate changes in metabolite profiles, which may reflect changes in metabolic pathways and provide information correlated with a specific biological process or pathophysiology. High-resolution (1)H NMR spectroscopy is used to identify metabolites in biofluids and tissue samples qualitatively and quantitatively. This pre-analytical study evaluated the effects of storage time and temperature on (1)H NMR spectra from human urine in two settings. Firstly, to evaluate short time effects probably due to acute delay in sample handling and secondly, the effect of prolonged storage up to one month to find markers of sample miss-handling. A number of statistical procedures were used to assess the differences between samples stored under different conditions, including Projection to Latent Structure Discriminant Analysis (PLS-DA), non-parametric testing as well as mixed effect linear regression analysis. The results indicate that human urine samples can be stored at 10 °C for 24 h or at -80 °C for 1 month, as no relevant changes in (1)H NMR fingerprints were observed during these time periods and temperature conditions. However, some metabolites most likely of microbial origin showed alterations during prolonged storage but without facilitating classification. In conclusion, the presented protocol for urine sample handling and semi-automatic metabolite quantification is suitable for large-scale epidemiological studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Preanalytical variables in measurement of free (ionized) calcium in lithium heparin-containing blood collection tubes.

PubMed

Haverstick, Doris M; Brill, Louis B; Scott, Mitchell G; Bruns, David E

2009-05-01

Measurements of free (ionized) calcium (iCa) are increasingly requested in patient care locations where immediate analysis is unavailable. Evacuated blood collection tubes containing lithium heparin and gel separator material are widely used in clinical laboratories, but little information is available on the effects of these tubes or of delay prior to analysis on the concentration or stability of iCa. We collected blood from volunteers into lithium-heparin tubes (PST, Vacutainer PST, BD Pre-Analytic Systems) of multiple lots and into electrolyte-balanced heparin syringes (Portex Dry Heparin, Smiths Medical). iCa was measured (Siemens 1265 blood gas analyzers) immediately and, in PST, at 0-7 h with or without transportation of the tubes from remote sites. The mean difference of free calcium results in the PST tubes and electrolyte-balanced syringes was -0.08 (95% confidence interval -0.17 to 0.012) mmol/l, and the SD of the residuals (Sy, x) of the regression was 0.03 mmol/l. There was no detectable lot-to-lot variation in results. Free calcium was stable in tubes at room temperature and at 4 degrees C for at least 7 h with or without transportation. iCa measured in the examined blood collection tubes is stable and unaffected by lot-to-lot variation of tubes, but results are slightly lower than with special blood gas syringes.

Dried Blood Spots - Preparing and Processing for Use in Immunoassays and in Molecular Techniques

PubMed Central

Grüner, Nico; Stambouli, Oumaima; Ross, R. Stefan

2015-01-01

The idea of collecting blood on a paper card and subsequently using the dried blood spots (DBS) for diagnostic purposes originated a century ago. Since then, DBS testing for decades has remained predominantly focused on the diagnosis of infectious diseases especially in resource-limited settings or the systematic screening of newborns for inherited metabolic disorders and only recently have a variety of new and innovative DBS applications begun to emerge. For many years, pre-analytical variables were only inappropriately considered in the field of DBS testing and even today, with the exception of newborn screening, the entire pre-analytical phase, which comprises the preparation and processing of DBS for their final analysis has not been standardized. Given this background, a comprehensive step-by-step protocol, which covers al the essential phases, is proposed, i.e., collection of blood; preparation of blood spots; drying of blood spots; storage and transportation of DBS; elution of DBS, and finally analyses of DBS eluates. The effectiveness of this protocol was first evaluated with 1,762 coupled serum/DBS pairs for detecting markers of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infections on an automated analytical platform. In a second step, the protocol was utilized during a pilot study, which was conducted on active drug users in the German cities of Berlin and Essen. PMID:25867233

A review of blood sample handling and pre-processing for metabolomics studies.

PubMed

Hernandes, Vinicius Veri; Barbas, Coral; Dudzik, Danuta

2017-09-01

Metabolomics has been found to be applicable to a wide range of clinical studies, bringing a new era for improving clinical diagnostics, early disease detection, therapy prediction and treatment efficiency monitoring. A major challenge in metabolomics, particularly untargeted studies, is the extremely diverse and complex nature of biological specimens. Despite great advances in the field there still exist fundamental needs for considering pre-analytical variability that can introduce bias to the subsequent analytical process and decrease the reliability of the results and moreover confound final research outcomes. Many researchers are mainly focused on the instrumental aspects of the biomarker discovery process, and sample related variables sometimes seem to be overlooked. To bridge the gap, critical information and standardized protocols regarding experimental design and sample handling and pre-processing are highly desired. Characterization of a range variation among sample collection methods is necessary to prevent results misinterpretation and to ensure that observed differences are not due to an experimental bias caused by inconsistencies in sample processing. Herein, a systematic discussion of pre-analytical variables affecting metabolomics studies based on blood derived samples is performed. Furthermore, we provide a set of recommendations concerning experimental design, collection, pre-processing procedures and storage conditions as a practical review that can guide and serve for the standardization of protocols and reduction of undesirable variation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantification of Inflammasome Adaptor Protein ASC in Biological Samples by Multiple-Reaction Monitoring Mass Spectrometry.

PubMed

Ulke-Lemée, Annegret; Lau, Arthur; Nelson, Michelle C; James, Matthew T; Muruve, Daniel A; MacDonald, Justin A

2018-06-09

Inflammation is an integral component of many diseases, including chronic kidney disease (CKD). ASC (apoptosis-associated speck-like protein containing CARD, also PYCARD) is the key inflammasome adaptor protein in the innate immune response. Since ASC specks, a macromolecular condensate of ASC protein, can be released by inflammasome-activated cells into the extracellular space to amplify inflammatory responses, the ASC protein could be an important biomarker in diagnostic applications. Herein, we describe the development and validation of a multiple reaction monitoring mass spectrometry (MRM-MS) assay for the accurate quantification of ASC in human biospecimens. Limits of detection and quantification for the signature DLLLQALR peptide (used as surrogate for the target ASC protein) were determined by the method of standard addition using synthetic isotope-labeled internal standard (SIS) peptide and urine matrix from a healthy donor (LOQ was 8.25 pM, with a ~ 1000-fold linear range). We further quantified ASC in the urine of CKD patients (8.4 ± 1.3 ng ASC/ml urine, n = 13). ASC was positively correlated with proteinuria and urinary IL-18 in CKD samples but not with urinary creatinine. Unfortunately, the ASC protein is susceptible to degradation, and patient urine that was thawed and refrozen lost 85% of the ASC signal. In summary, the MRM-MS assay provides a robust means to quantify ASC in biological samples, including clinical biospecimens; however, sample collection and storage conditions will have a critical impact on assay reliability.

Survey Field Methods for Expanded Biospecimen and Biomeasure Collection in NSHAP Wave 2

PubMed Central

Jaszczak, Angela; Hoffmann, Joscelyn N.; You, Hannah M.; Kern, David W.; Pagel, Kristina; McPhillips, Jane; Schumm, L. Philip; Dale, William; Huang, Elbert S.; McClintock, Martha K.

2014-01-01

Objectives. The National Social Life, Health, and Aging Project is a nationally representative, longitudinal survey of older adults. A main component is the collection of biomeasures to objectively assess physiological status relevant to psychosocial variables, aging conditions, and disease. Wave 2 added novel biomeasures, refined those collected in Wave 1, and provides a reference for the collection protocols and strategy common to the biomeasures. The effects of aging, gender, and their interaction are presented in the specific biomeasure papers included in this Special Issue. Method. A transdisciplinary working group expanded the biomeasures collected to include physiological, genetic, anthropometric, functional, neuropsychological, and sensory measures, yielding 37 more than in Wave 1. All were designed for collection in respondents’ homes by nonmedically trained field interviewers. Results. Both repeated and novel biomeasures were successful. Those in Wave 1 were refined to improve quality, and ensure consistency for longitudinal analysis. Four new biospecimens yielded 27 novel measures. During the interview, 19 biomeasures were recorded covering anthropometric, functional, neuropsychological, and sensory measures and actigraphy provided data on activity and sleep. Discussion. Improved field methods included in-home collection, temperature control, establishment of a central survey biomeasure laboratory, and shipping, all of which were crucial for successful collection by the field interviewers and accurate laboratory assay of the biomeasures (92.1% average co-operation rate and 97.3% average assay success rate). Developed for home interviews, these biomeasures are readily applicable to other surveys. PMID:25360025

Genomics, Telomere Length, Epigenetics, and Metabolomics in the Nurses’ Health Studies

PubMed Central

Aschard, Hugues; De Vivo, Immaculata; Michels, Karin B.; Kraft, Peter

2016-01-01

Objectives. To review the contribution of the Nurses’ Health Study (NHS) and NHS II to genomics, epigenetics, and metabolomics research. Methods. We performed a narrative review of the publications of the NHS and NHS II between 1990 and 2016 based on biospecimens, including blood and tumor tissue, collected from participants. Results. The NHS has contributed to the discovery of genetic loci influencing more than 45 complex human phenotypes, including cancers, diabetes, cardiovascular disease, reproductive characteristics, and anthropometric traits. The combination of genomewide genotype data with extensive exposure and lifestyle data has enabled the evaluation of gene–environment interactions. Furthermore, data suggest that longer telomere length increases risk of cancers not related to smoking, and that modifiable factors (e.g., diet) may have an impact on telomere length. “Omics” research in the NHS continues to expand, with epigenetics and metabolomics becoming greater areas of focus. Conclusions. The combination of prospective biomarker data and broad exposure information has enabled the NHS to participate in a variety of “omics” research, contributing to understanding of the epidemiology and biology of multiple complex diseases. PMID:27459442

Genomics, Telomere Length, Epigenetics, and Metabolomics in the Nurses' Health Studies.

PubMed

Townsend, Mary K; Aschard, Hugues; De Vivo, Immaculata; Michels, Karin B; Kraft, Peter

2016-09-01

To review the contribution of the Nurses' Health Study (NHS) and NHS II to genomics, epigenetics, and metabolomics research. We performed a narrative review of the publications of the NHS and NHS II between 1990 and 2016 based on biospecimens, including blood and tumor tissue, collected from participants. The NHS has contributed to the discovery of genetic loci influencing more than 45 complex human phenotypes, including cancers, diabetes, cardiovascular disease, reproductive characteristics, and anthropometric traits. The combination of genomewide genotype data with extensive exposure and lifestyle data has enabled the evaluation of gene-environment interactions. Furthermore, data suggest that longer telomere length increases risk of cancers not related to smoking, and that modifiable factors (e.g., diet) may have an impact on telomere length. "Omics" research in the NHS continues to expand, with epigenetics and metabolomics becoming greater areas of focus. The combination of prospective biomarker data and broad exposure information has enabled the NHS to participate in a variety of "omics" research, contributing to understanding of the epidemiology and biology of multiple complex diseases.

Adhesive blood microsampling systems for steroid measurement via LC-MS/MS in the rat.

PubMed

Heussner, Kirsten; Rauh, Manfred; Cordasic, Nada; Menendez-Castro, Carlos; Huebner, Hanna; Ruebner, Matthias; Schmidt, Marius; Hartner, Andrea; Rascher, Wolfgang; Fahlbusch, Fabian B

2017-04-01

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) allows for the direct analysis of multiple hormones in a single probe with minimal sample volume. Rodent-based animal studies strongly rely on microsampling, such as the dry blood spot (DBS) method. However, DBS suffers the drawback of hematocrit-dependence (non-volumetric). Hence, novel volumetric microsampling techniques were introduced recently, allowing sampling of fixed accurate volumes. We compared these methods for steroid analysis in the rat to improve inter-system comparability. We analyzed steroid levels in blood using the absorptive microsampling devices Whatman® 903 Protein Saver Cards, Noviplex™ Plasma Prep Cards and the Mitra™ Microsampling device and compared the obtained results to the respective EDTA plasma levels. Quantitative steroid analysis was performed via LC-MS/MS. For the determination of the plasma volume factor for each steroid, their levels in pooled blood samples from each human adults and rats (18weeks) were compared and the transferability of these factors was evaluated in a new set of juvenile (21days) and adult (18weeks) rats. Hematocrit was determined concomitantly. Using these approaches, we were unable to apply one single volume factor for each steroid. Instead, plasma volume factors had to be adjusted for the recovery rate of each steroid and device individually. The tested microsampling systems did not allow the use of one single volume factor for adult and juvenile rats based on an unexpectedly strong hematocrit-dependency and other steroid specific (pre-analytic) factors. Our study provides correction factors for LC-MS/MS steroid analysis of volumetric and non-volumetric microsampling systems in comparison to plasma. It argues for thorough analysis of chromatographic effects before the use of novel volumetric systems for steroid analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Key factors influencing the incidence of hemolysis: A critical appraisal of current evidence.

PubMed

McCaughey, Euan James; Vecellio, Elia; Lake, Rebecca; Li, Ling; Burnett, Leslie; Chesher, Douglas; Braye, Stephen; Mackay, Mark; Gay, Stephanie; Badrick, Tony; Westbrook, Johanna; Georgiou, Andrew

2017-01-01

Hemolysis is a leading cause of pre-analytical laboratory errors. The identification of contributing factors is an important step towards the development of effective practices to reduce and prevent hemolysis. We performed a review of PUBMED, Embase, Medline and CINAHL to identify articles published between January 2000 and August 2016 that identified factors influencing in vitro hemolysis rates. The 40 studies included in this review provide excellent evidence that hemolysis rates are higher in Emergency Departments (EDs), for non-antecubital draws, for specimens drawn using an intravenous catheter compared to venipuncture and for samples transported by pneumatic tube compared to by hand. There is also good evidence that hemolysis rates are higher when specimens are not collected by professional phlebotomists, larger volume specimen tubes are used, specimen tubes are filled less than halfway and tourniquet time is greater than one minute. The results of this review suggest that hospitals and clinical laboratories should consider deploying phlebotomists in EDs, drawing all blood through a venipuncture, using the antecubital region as the optimum blood collection site and transporting specimens by laboratory assistant/other personnel, or if this in not practical, ensuring that pneumatic transport systems are validated, maintained and monitored. Studies also recommend making hemolysis a hospital-wide issue and ensuring high-quality staff training and adherence to standard operating procedures to reduce hemolysis rates. Awareness of the factors that influence hemolysis rates, and adoption of strategies to mitigate these risk factors, is an important step towards creating quality practices to reduce hemolysis rates and improve the quality of patient care.

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2014-10-01

Y N 0.519 60 70 5 2 2 1.620 2 0.250 2 Yes - Current Smoker AF Jet fuel , Second-hand smoke Jet fuel , Second-hand smoke S0018 Squamous Cell...Second-hand smoke Second-hand smoke S0028 Squamous Cell Carcinoma Stage IIIB N N No - Quit Smoking 150 AF Jet fuel , Nuclear weapons, Second-hand... Jet fuel , Nuclear weapons, Second-hand S0029 Squamous Cell Carcinoma Stage IIA Y N 0.06 100 40 0 1 3 .571 1 8 .043 1 No - Quit Smoking AR Second

Standardization of collection requirements for fasting samples: for the Working Group on Preanalytical Phase (WG-PA) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM).

PubMed

Simundic, A M; Cornes, M; Grankvist, K; Lippi, G; Nybo, M

2014-05-15

Standardized protocols for patient preparation for laboratory testing are currently lacking. Moreover, a great heterogeneity exists in the definitions of "fasting" currently being used among healthcare workers and in the literature. Marked metabolic and hormonal changes occur after food ingestion, mainly due to the absorption of fluids, lipids, proteins, carbohydrates and other food constituents. This postprandial response varies markedly in response to numerous factors, such as eating behavior, food composition, fasting duration, time of the day, chronic and acute smoking, coffee and alcohol consumption. It is therefore crucial to minimize the total variability by controlling as many of these modifying factors as possible. Control of the abovementioned effects on postprandial response can only be achieved by standardizing the way patients are prepared for laboratory testing, i.e. by defining the fasting duration, as well as what is and what is not allowed (e.g., coffee, tea, smoking, water) during the period of fasting prior to sample collection. The aim of this article is to describe the range of effects of different approaches to fasting on laboratory tests, and to provide a framework for the harmonization of definitions for fasting requirements for laboratory tests. Copyright © 2013 Elsevier B.V. All rights reserved.

Approaches in methodology for population-based longitudinal study on neuroprotective model for healthy longevity (TUA) among Malaysian Older Adults.

PubMed

Shahar, Suzana; Omar, Azahadi; Vanoh, Divya; Hamid, Tengku Aizan; Mukari, Siti Zamratol Mai-Sarah; Din, Normah Che; Rajab, Nor Fadilah; Mohammed, Zainora; Ibrahim, Rahimah; Loo, Won Hui; Meramat, Asheila; Kamaruddin, Mohd Zul Amin; Bagat, Mohamad Fazdillah; Razali, Rosdinom

2016-12-01

A number of longitudinal studies on aging have been designed to determine the predictors of healthy longevity, including the neuroprotective factors, however, relatively few studies included a wide range of factors and highlighted the challenges faced during data collection. Thus, the longitudinal study on neuroprotective model for healthy longevity (LRGS TUA) has been designed to prospectively investigate the magnitude of cognitive decline and its risk factors through a comprehensive multidimensional assessment comprising of biophysical health, auditory and visual function, nutrition and dietary pattern and psychosocial aspects. At baseline, subjects were interviewed for their status on sociodemographic, health, neuropsychological test, psychosocial and dietary intake. Subjects were also measured for anthropometric and physical function and fitness. Biospecimens including blood, buccal swap, hair and toenail were collected, processed and stored. A subsample was assessed for sensory function, i.e., vision and auditory. During follow-up, at 18 and 36 months, most of the measurements, along with morbidity and mortality outcomes will be collected. The description of mild cognitive impairment, successful aging and usual aging process is presented here. A total 2322 respondents were recruited in the data analysis at baseline. Most of the respondents were categorized as experiencing usual aging (73 %), followed by successful aging (11 %) and mild cognitive impairment (16 %). The LRGS TUA study is the most comprehensive longitudinal study on aging in Malaysia, and will contribute to the understanding of the aging process and factors associated with healthy aging and mental well-being of a multiethnic population in Malaysia.

The Henry Ford Production System: LEAN Process Redesign Improves Service in the Molecular Diagnostic Laboratory

PubMed Central

Cankovic, Milena; Varney, Ruan C.; Whiteley, Lisa; Brown, Ron; D'Angelo, Rita; Chitale, Dhananjay; Zarbo, Richard J.

2009-01-01

Accurate and timely molecular test results play an important role in patient management; consequently, there is a customer expectation of short testing turnaround times. Baseline data analysis revealed that the greatest challenge to timely result generation occurred in the preanalytic phase of specimen collection and transport. Here, we describe our efforts to improve molecular testing turnaround times by focusing primarily on redesign of preanalytic processes using the principles of LEAN production. Our goal was to complete greater than 90% of the molecular tests in less than 3 days. The project required cooperation from different laboratory disciplines as well as individuals outside of the laboratory. The redesigned processes involved defining and standardizing the protocols and approaching blood and tissue specimens as analytes for molecular testing. The LEAN process resulted in fewer steps, approaching the ideal of a one-piece flow for specimens through collection/retrieval, transport, and different aspects of the testing process. The outcome of introducing the LEAN process has been a 44% reduction in molecular test turnaround time for tissue specimens, from an average of 2.7 to 1.5 days. In addition, extending LEAN work principles to the clinician suppliers has resulted in a markedly increased number of properly collected and shipped blood specimens (from 50 to 87%). These continuous quality improvements were accomplished by empowered workers in a blame-free environment and are now being sustained with minimal management involvement. PMID:19661386

Cytological preparations for molecular analysis: A review of technical procedures, advantages and limitations for referring samples for testing.

PubMed

da Cunha Santos, G; Saieg, M A; Troncone, G; Zeppa, P

2018-04-01

Minimally invasive procedures such as endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) must yield not only good quality and quantity of material for morphological assessment, but also an adequate sample for analysis of molecular markers to guide patients to appropriate targeted therapies. In this context, cytopathologists worldwide should be familiar with minimum requirements for refereeing cytological samples for testing. The present manuscript is a review with comprehensive description of the content of the workshop entitled Cytological preparations for molecular analysis: pre-analytical issues for EBUS TBNA, presented at the 40th European Congress of Cytopathology in Liverpool, UK. The present review emphasises the advantages and limitations of different types of cytology substrates used for molecular analysis such as archival smears, liquid-based preparations, archival cytospin preparations and FTA (Flinders Technology Associates) cards, as well as their technical requirements/features. These various types of cytological specimens can be successfully used for an extensive array of molecular studies, but the quality and quantity of extracted nucleic acids rely directly on adequate pre-analytical assessment of those samples. In this setting, cytopathologists must not only be familiar with the different types of specimens and associated technical procedures, but also correctly handle the material provided by minimally invasive procedures, ensuring that there is sufficient amount of material for a precise diagnosis and correct management of the patient through personalised care. © 2018 John Wiley & Sons Ltd.

Two methods for proteomic analysis of formalin-fixed, paraffin embedded tissue result in differential protein identification, data quality, and cost.

PubMed

Luebker, Stephen A; Wojtkiewicz, Melinda; Koepsell, Scott A

2015-11-01

Formalin-fixed paraffin-embedded (FFPE) tissue is a rich source of clinically relevant material that can yield important translational biomarker discovery using proteomic analysis. Protocols for analyzing FFPE tissue by LC-MS/MS exist, but standardization of procedures and critical analysis of data quality is limited. This study compared and characterized data obtained from FFPE tissue using two methods: a urea in-solution digestion method (UISD) versus a commercially available Qproteome FFPE Tissue Kit method (Qkit). Each method was performed independently three times on serial sections of homogenous FFPE tissue to minimize pre-analytical variations and analyzed with three technical replicates by LC-MS/MS. Data were evaluated for reproducibility and physiochemical distribution, which highlighted differences in the ability of each method to identify proteins of different molecular weights and isoelectric points. Each method replicate resulted in a significant number of new protein identifications, and both methods identified significantly more proteins using three technical replicates as compared to only two. UISD was cheaper, required less time, and introduced significant protein modifications as compared to the Qkit method, which provided more precise and higher protein yields. These data highlight significant variability among method replicates and type of method used, despite minimizing pre-analytical variability. Utilization of only one method or too few replicates (both method and technical) may limit the subset of proteomic information obtained. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Laboratory testing of extravascular body fluids in Croatia: a survey of the Working group for extravascular body fluids of the Croatian Society of Medical Biochemistry and Laboratory Medicine.

PubMed

Kopcinovic, Lara Milevoj; Vogrinc, Zeljka; Kocijan, Irena; Culej, Jelena; Aralica, Merica; Jokic, Anja; Antoncic, Dragana; Bozovic, Marija

2016-10-15

We hypothesized that extravascular body fluid (EBF) analysis in Croatia is not harmonized and aimed to investigate preanalytical, analytical and postanalytical procedures used in EBF analysis in order to identify key aspects that should be addressed in future harmonization attempts. An anonymous online survey created to explore laboratory testing of EBF was sent to secondary, tertiary and private health care Medical Biochemistry Laboratories (MBLs) in Croatia. Statements were designed to address preanalytical, analytical and postanalytical procedures of cerebrospinal, pleural, peritoneal (ascites), pericardial, seminal, synovial, amniotic fluid and sweat. Participants were asked to declare the strength of agreement with proposed statements using a Likert scale. Mean scores for corresponding separate statements divided according to health care setting were calculated and compared. The survey response rate was 0.64 (58 / 90). None of the participating private MBLs declared to analyse EBF. We report a mean score of 3.45 obtained for all statements evaluated. Deviations from desirable procedures were demonstrated in all EBF testing phases. Minor differences in procedures used for EBF analysis comparing secondary and tertiary health care MBLs were found. The lowest scores were obtained for statements regarding quality control procedures in EBF analysis, participation in proficiency testing programmes and provision of interpretative comments on EBF's test reports. Although good laboratory EBF practice is present in Croatia, procedures for EBF analysis should be further harmonized to improve the quality of EBF testing and patient safety.

Assuring the Quality of Test Results in the Field of Nuclear Techniques and Ionizing Radiation. The Practical Implementation of Section 5.9 of the EN ISO/IEC 17025 Standard

NASA Astrophysics Data System (ADS)

Cucu, Daniela; Woods, Mike

2008-08-01

The paper aims to present a practical approach for testing laboratories to ensure the quality of their test results. It is based on the experience gained in assessing a large number of testing laboratories, discussing with management and staff, reviewing results obtained in national and international PTs and ILCs and exchanging information in the EA laboratory committee. According to EN ISO/IEC 17025, an accredited laboratory has to implement a programme to ensure the quality of its test results for each measurand. Pre-analytical, analytical and post-analytical measures shall be applied in a systematic manner. They shall include both quality control and quality assurance measures. When designing the quality assurance programme a laboratory should consider pre-analytical activities (like personnel training, selection and validation of test methods, qualifying equipment), analytical activities ranging from sampling, sample preparation, instrumental analysis and post-analytical activities (like decoding, calculation, use of statistical tests or packages, management of results). Designed on different levels (analyst, quality manager and technical manager), including a variety of measures, the programme shall ensure the validity and accuracy of test results, the adequacy of the management system, prove the laboratory's competence in performing tests under accreditation and last but not least show the comparability of test results. Laboratory management should establish performance targets and review periodically QC/QA results against them, implementing appropriate measures in case of non-compliance.

[Modal failure analysis and effects in the detection of errors in the transport of samples to the clinical laboratory].

PubMed

Parés-Pollán, L; Gonzalez-Quintana, A; Docampo-Cordeiro, J; Vargas-Gallego, C; García-Álvarez, G; Ramos-Rodríguez, V; Diaz Rubio-García, M P

2014-01-01

Owing to the decrease in values of biochemical glucose parameter in some samples from external extraction centres, and the risk this implies to patient safety; it was decided to apply an adaptation of the «Health Services Failure Mode and Effects Analysis» (HFMEA) to manage risk during the pre-analytical phase of sample transportation from external centres to clinical laboratories. A retrospective study of glucose parameter was conducted during two consecutive months. The analysis was performed in its different phases: to define the HFMEA topic, assemble the team, graphically describe the process, conduct a hazard analysis, design the intervention and indicators, and identify a person to be responsible for ensuring completion of each action. The results of glucose parameter in one of the transport routes, were significantly lower (P=.006). The errors and potential causes of this problem were analysed, and criteria of criticality and detectability were applied (score≥8) in the decision tree. It was decided to: develop a document management system; reorganise extractions and transport routes in some centres; quality control of the sample container ice-packs, and the time and temperature during transportation. This work proposes quality indicators for controlling time and temperature of transported samples in the pre-analytical phase. Periodic review of certain laboratory parameters can help to detect problems in transporting samples. The HFMEA technique is useful for the clinical laboratory. Copyright © 2013 SECA. Published by Elsevier Espana. All rights reserved.

Transmissive liquid-crystal device correcting primary coma aberration and astigmatism in laser scanning microscopy

NASA Astrophysics Data System (ADS)

Tanabe, Ayano; Hibi, Terumasa; Ipponjima, Sari; Matsumoto, Kenji; Yokoyama, Masafumi; Kurihara, Makoto; Hashimoto, Nobuyuki; Nemoto, Tomomi

2016-03-01

Laser scanning microscopy allows 3D cross-sectional imaging inside biospecimens. However, certain aberrations produced can degrade the quality of the resulting images. We previously reported a transmissive liquid-crystal device that could compensate for the predominant spherical aberrations during the observations, particularly in deep regions of the samples. The device, inserted between the objective lens and the microscope revolver, improved the image quality of fixed-mouse-brain slices that were observed using two-photon excitation laser scanning microscopy, which was originally degraded by spherical aberration. In this study, we developed a transmissive device that corrects primary coma aberration and astigmatism, motivated by the fact that these asymmetric aberrations can also often considerably deteriorate image quality, even near the sample surface. The device's performance was evaluated by observing fluorescent beads using single-photon excitation laser scanning microscopy. The fluorescence intensity in the image of the bead under a cover slip tilted in the y-direction was increased by 1.5 times after correction by the device. Furthermore, the y- and z-widths of the imaged bead were reduced to 66% and 65%, respectively. On the other hand, for the imaged bead sucked into a glass capillary in the longitudinal x-direction, correction with the device increased the fluorescence intensity by 2.2 times compared to that of the aberrated image. In addition, the x-, y-, and z-widths of the bead image were reduced to 75%, 53%, and 40%, respectively. Our device successfully corrected several asymmetric aberrations to improve the fluorescent signal and spatial resolution, and might be useful for observing various biospecimens.

Hepatocellular carcinoma Early Detection Strategy study — EDRN Public Portal

Cancer.gov

Part 1: The first part of this study is to conduct follow-up for patients that were enrolled in the EDRN Phase 2 Validation Study called DCP (13). For this part of the study, four groups are defined as follows: a) Vanguard Controls are cirrhotic controls, from the Phase 2 trial that have not developed HCC and sign a new consent form for HEDS participation. These patients will be followed for a minimum of an additional 24 months and have biospecimens collected every 6 months. b) Vanguard Interval Controls are cirrhotic controls, from the Phase 2 trial that have not developed HCC and do not sign a new consent form for HEDS participation. This group will have outcome data abstracted from their medical records. c) Vanguard Interval Cases are cirrhotic controls from the Phase 2 trial that developed HCC after completion of the Phase 2 trial but prior to the current study. This group will have outcome data abstracted from their medical records. d) Vanguard Cases are HCC cases from the Phase 2 trial. This group will have outcome data abstracted from their medical records. Part 2: New Controls - The second part of this study is the new accrual of cirrhotic controls at the seven participating sites. These patients will be followed for a minimum of 24 months and have biospecimens collected every 6 months. Data will be collected every 6 months: ultrasound, AFP, liver function tests, complete blood counts, MELD scores and any changes in medical history, personal cancer history and family cancer history.

The NINDS Parkinson's disease biomarkers program: The Ninds Parkinson's Disease Biomarkers Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthal, Liana S.; Drake, Daniel; Alcalay, Roy N.

Background: Neuroprotection for Parkinson Disease (PD) remains elusive. Biomarkers hold the promise of removing roadblocks to therapy development. The National Institute of Neurological Disorders and Stroke (NINDS) has therefore established the Parkinson’s Disease Biomarkers Program (PDBP) to promote discovery of biomarkers for use in phase II-III clinical trials in PD. Methods: The PDBP facilitates biomarker development to improve neuroprotective clinical trial design, essential for advancing therapeutics for PD. To date, eleven consortium projects in the PDBP are focused on the development of clinical and laboratory-based PD biomarkers for diagnosis, progression tracking, and/or the prediction of prognosis. Seven of these projectsmore » also provide detailed longitudinal data and biospecimens from PD patients and controls, as a resource for all PD researchers. Standardized operating procedures and pooled reference samples have been created in order to allow cross-project comparisons and assessment of batch effects. A web-based Data Management Resource facilitates rapid sharing of data and biosamples across the entire PD research community for additional biomarker projects. Results: Here we describe the PDBP, highlight standard operating procedures for the collection of biospecimens and data, and provide an interim report with quality control analysis on the first 1082 participants and 1033 samples with quality control analysis collected as of October 2014. Conclusions: By making samples and data available to academics and industry, encouraging the adoption of existing standards, and providing a resource which complements existing programs, the PDBP will accelerate the pace of PD biomarker research, with the goal of improving diagnostic methods and treatment.« less

Community-Based Participatory Research Integrates Behavioral and Biological Research to Achieve Health Equity for Native Hawaiians.

PubMed

Townsend, Claire K M; Dillard, Adrienne; Hosoda, Kelsea K; Maskarinec, Gregory G; Maunakea, Alika K; Yoshimura, Sheryl R; Hughes, Claire; Palakiko, Donna-Marie; Kehauoha, Bridget Puni; Kaholokula, Joseph Keawe'aimoku

2015-12-22

Native Hawaiians bear a disproportionate burden of type-2 diabetes and related complications compared to all other groups in Hawai'i (e.g., Whites, Japanese, Korean). Distrust in these communities is a significant barrier to participation in epigenetic research studies seeking to better understand disease processes. The purpose of this paper is to describe the community-based participatory research (CBPR) approach and research process we employed to integrate behavior and biological sciences with community health priorities. A CBPR approach was used to test a 3-month evidence-based, diabetes self-management intervention (N = 65). To investigate the molecular mechanisms linking inflammation with glucose homeostasis, a subset of participants (n = 16) provided peripheral blood mononuclear cells. Community and academic researchers collaborated on research design, assessment protocols, and participant recruitment, prioritizing participants' convenience and education and strictly limiting the use of the data collected. Preliminary results indicate significant changes in DNA methylation at gene regions associated with inflammation and diabetes signaling pathways and significant improvements in hemoglobin A1c, self-care activities, and diabetes distress and understanding. This study integrates community, behavioral, and epigenomic expertise to better understand the outcomes of a diabetes self-management intervention. Key lessons learned suggest the studies requiring biospecimen collection in indigenous populations require community trust of the researchers, mutual benefits for the community and researchers, and for the researchers to prioritize the community's needs. CBPR may be an important tool in providing communities the voice and protections to participate in studies requiring biospecimens.

The Ontario Birth Study: A prospective pregnancy cohort study integrating perinatal research into clinical care.

PubMed

Anderson, Laura N; Knight, Julia A; Hung, Rayjean J; Hewko, Sheryl L; Seeto, Ryan A; Martin, Mary-Jean; Fleming, Alison; Maguire, Jonathon L; Matthews, Stephen G; Murphy, Kellie E; Okun, Nan; Jenkins, Jennifer M; Lye, Stephen J; Bocking, Alan

2018-05-01

Pregnancy and early childhood represent critical periods that impact health throughout the life-course. The Ontario Birth Study (OBS) is a pregnancy cohort study designed as a platform for research on pregnancy complications, maternal and infant health, and the developmental origins of health and disease. Pregnant women <17 weeks gestational age were recruited between 2013 and 2015 from antenatal clinics at Mount Sinai Hospital, Toronto, Canada. Life style and diet questionnaires, biospecimens, and clinical data were collected throughout the pregnancy and postpartum period at the time of clinical care. The OBS was integrated into clinical care to reduce participant burden, improve efficiency, and increase research potential. There were 3181 eligible women approached for recruitment and 1374 (43%) participated in the study. Among the 1374 participants, 1272 (93%) delivered a liveborn infant and were followed to 6-10 weeks postpartum. Of the 1272 women who completed the study, 98% had at least one pregnancy blood sample collected, 97% had vaginal swabs collected, 90% completed the prenatal life style questionnaires, and 78% completed the Diet History Questionnaire. Most women (88%) were ≥30 years of age, 55% had no previous children, 24% were overweight or obese pre-pregnancy and 78% of parents had postsecondary education. Most pregnancies were singleton (3% twins), 34% delivered by caesarean section, and 6% preterm (<37 weeks gestation). The OBS is a contemporary cohort with detailed data including banked biospecimens for studies of pregnancy health and the gene-environment interactions that establish developmental trajectories to health, learning, and social functioning. © 2018 John Wiley & Sons Ltd.

The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and Its Associated Research Resource

PubMed Central

2013-01-01

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large-scale research effort conducted by the National Cancer Institute. PLCO offers an example of coordinated research by both the extramural and intramural communities of the National Institutes of Health. The purpose of this article is to describe the PLCO research resource and how it is managed and to assess the productivity and the costs associated with this resource. Such an in-depth analysis of a single large-scale project can shed light on questions such as how large-scale projects should be managed, what metrics should be used to assess productivity, and how costs can be compared with productivity metrics. A comprehensive publication analysis identified 335 primary research publications resulting from research using PLCO data and biospecimens from 2000 to 2012. By the end of 2012, a total of 9679 citations (excluding self-citations) have resulted from this body of research publications, with an average of 29.7 citations per article, and an h index of 45, which is comparable with other large-scale studies, such as the Nurses’ Health Study. In terms of impact on public health, PLCO trial results have been used by the US Preventive Services Task Force in making recommendations concerning prostate and ovarian cancer screening. The overall cost of PLCO was $454 million over 20 years, adjusted to 2011 dollars, with approximately $37 million for the collection, processing, and storage of biospecimens, including blood samples, buccal cells, and pathology tissues. PMID:24115361

HER2 testing of gastro-oesophageal adenocarcinoma: a commentary and guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee.

PubMed

Wong, Newton A C S; Amary, Fernanda; Butler, Rachel; Byers, Richard; Gonzalez, David; Haynes, Harry R; Ilyas, Mohammad; Salto-Tellez, Manuel; Taniere, Philippe

2018-05-01

The use of biologics targeted to the human epidermal growth factor receptor 2 (HER2) protein is the latest addition to the armamentarium used to fight advanced gastric or gastro-oesophageal junction adenocarcinoma. The decision to treat with the biologic trastuzumab is completely dependent on HER2 testing of tumour tissue. In 2017, the College of American Pathologists, American Society for Clinical Pathology and the American Society of Clinical Oncology jointly published guidelines for HER2 testing and clinical decision making in gastro-oesophageal adenocarcinoma. The Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee has issued the following document as a commentary of these guidelines and, in parallel, to provide guidance on HER2 testing in National Health Service pathology departments within the UK. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such HER2 testing. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Survey of national guidelines, education and training on phlebotomy in 28 European countries: an original report by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PA).

PubMed

Simundic, Ana-Maria; Cornes, Michael; Grankvist, Kjell; Lippi, Giuseppe; Nybo, Mads; Kovalevskaya, Svjetlana; Sprongl, Ludek; Sumarac, Zorica; Church, Stephen

2013-08-01

European questionnaire survey was conducted by the European Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Preanalytical Phase (EFLM WG-PA) to assess how phlebotomy is performed in EFLM countries, including differences in personnel, level of education and skills, and to investigate the presence and compliance of national phlebotomy guidelines on this matter. A questionnaire was constructed containing questions elucidating different aspects of the organization behind the phlebotomy praxis on a national basis, including questions on the staff performing phlebotomy, the education of these staff members, and the existence of and adherence to national guidelines. All 39 EFLM member countries were invited to participate. In total 28/39 (72%) EFLM member countries responded. Seven out of the 28 (25%) have national phlebotomy guidelines and five have implemented other guidelines. The estimated compliance with phlebotomy guidance for the laboratories in the countries that have national guidelines available is poor, regardless to whether the phlebotomy was under the laboratory control or not. Most countries were interested in EFLM guidelines and to participate in a pilot EFLM preanalytical phase external quality assessment (EQA) scheme. In the responding EFLM member countries, the majority of phlebotomy is performed by nurses and laboratory technicians. Their basic education is generally 4-5 years of high school, followed by 2-5 years of colleague or university studies. Only a third (10/28; 36%) of the participating member countries has any specific training available as a continuous educational resource. A specific training for phlebotomy is not part of the education required to become qualified in 6/28 (21%) and 9/28 (32%) of countries for nurses and laboratory technicians, respectively. In countries and professions where training is required, most require more than 5 h of training. Based on the results of this survey we conclude the following: 1) There is a need to assess the quality of current practices, compliance to the CLSI H3-A6 guidelines and to identify some most critical steps which occur during phlebotomy, in different healthcare settings, across Europe; 2) Existing CLSI H3-A6 phlebotomy guidelines should be adapted and used locally in all European countries which do not have their own guidelines; 3) National EFLM societies need to be engaged in basic training program development and continuous education of healthcare phlebotomy staff (implementing the certification of competence).

Quality of blood culture testing - a survey in intensive care units and microbiological laboratories across four European countries

PubMed Central

2013-01-01

Introduction Blood culture (BC) testing before initiation of antimicrobial therapy is recommended as a standard of care in international sepsis guidelines and has been shown to reduce intensive care unit (ICU) stay, antibiotic use, and costs in hospitalized patients. Whereas microbiological laboratory practice has been highly standardized, shortfalls in the preanalytic procedures in the ICU (that is indication, time-to-incubation, blood volume and numbers of BC sets) have a significant effect on the diagnostic yield. The objective of this study was to gain insights into current practices regarding BC testing in intensive care units. Methods Qualitative survey, data collection by 138 semi-structured telephone interviews in four European countries (Italy, UK, France and Germany) between September and November 2009 in 79 clinical microbiology laboratories (LABs) and 59 ICUs. Results Whereas BC testing is expected to remain the gold standard for sepsis diagnostics in all countries, there are substantial differences regarding preanalytic procedures. The decision to launch BC testing is carried out by physicians vs. ICU nurses in the UK in 92 vs. 8%, in France in 75 vs. 25%, in Italy in 88 vs. 12% and in Germany in 92 vs. 8%. Physicians vs. nurses collect BCs in the UK in 77 vs. 23%, in France in 0 vs. 100%, in Italy in 6 vs. 94% and in Germany in 54 vs. 46%. The mean time from blood collection to incubation in the UK is 2 h, in France 3 h, in Italy 4 h, but 20 h in German remote LABs (2 h in in-house LABs), due to the large number of remote nonresident microbiological laboratories in Germany. There were major differences between the perception of the quality of BC testing between ICUs and LABs. Among German ICU respondents, 62% reported that they have no problems with BC testing, 15% reported time constraints, 15% cost pressure, and only 8% too long time to incubation. However, the corresponding LABs of these German ICUs reported too many false positive results due to preanalytical contaminations (49%), insufficient numbers of incoming BC sets (47%), long transportation time (41%) or cost pressure (18%). Conclusions There are considerable differences in the quality of BC testing across European countries. In Germany, time to incubation is a considerable problem due to the increasing number of remote LABs. This is a major issue of concern to physicians aiming to implement sepsis guidelines in the ICUs. PMID:24144084

Frequent alteration of the protein synthesis of enzymes for glucose metabolism in hepatocellular carcinomas.

PubMed

Shimizu, Takayuki; Inoue, Ken-ichi; Hachiya, Hiroyuki; Shibuya, Norisuke; Shimoda, Mitsugi; Kubota, Keiichi

2014-09-01

Cancer cells show enhanced glycolysis and inhibition of oxidative phosphorylation, even in the presence of sufficient oxygen (aerobic glycolysis). Glycolysis is much less efficient for energy production than oxidative phosphorylation, and the reason why cancer cells selectively use glycolysis remains unclear. Biospecimens were collected from 45 hepatocellular carcinoma patients. Protein samples were prepared through subcellular localization or whole-cell lysis. Protein synthesis was measured by SDS-PAGE and immunoblotting. mRNA transcription was measured using quantitative RT-PCR. Statistical correlation among immunoblotting data and clinicolaboratory factors were analyzed using SPSS. Enzymes for oxidative phosphorylation (SDHA and SDHB) were frequently decreased (56 and 48 % of patients, respectively) in hepatocellular carcinomas. The lowered amount of the SDH protein complex was rarely accompanied by stabilization of HIF1α and subsequent activation of the hypoxia response. On the other hand, protein synthesis of G6PD and TKT, enzymes critical for pentose phosphate pathway (PPP), was increased (in 45 and 55 % of patients, respectively), while that of ALDOA, an enzyme for mainstream glycolysis, was eliminated (in 55 % of patients). Alteration of protein synthesis was correlated with gene expression for G6PD and TKT, but not for TKTL1, ALDOA, SDHA or SDHB. Augmented transcription and synthesis of PPP enzymes were accompanied by nuclear accumulation of NRF2. Hepatocellular carcinomas divert glucose metabolism to the anabolic shunt by activating transcription factor NRF2.

The effectiveness of cooling conditions on temperature of canine EDTA whole blood samples

PubMed Central

Sun, Xiaocun; Flatland, Bente

2016-01-01

Background Preanalytic factors such as time and temperature can have significant effects on laboratory test results. For example, ammonium concentration will increase 31% in blood samples stored at room temperature for 30 min before centrifugation. To reduce preanalytic error, blood samples may be placed in precooled tubes and chilled on ice or in ice water baths; however, the effectiveness of these modalities in cooling blood samples has not been formally evaluated. The purpose of this study was to evaluate the effectiveness of various cooling modalities on reducing temperature of EDTA whole blood samples. Methods Pooled samples of canine EDTA whole blood were divided into two aliquots. Saline was added to one aliquot to produce a packed cell volume (PCV) of 40% and to the second aliquot to produce a PCV of 20% (simulated anemia). Thirty samples from each aliquot were warmed to 37.7 °C and cooled in 2 ml allotments under one of three conditions: in ice, in ice after transfer to a precooled tube, or in an ice water bath. Temperature of each sample was recorded at one minute intervals for 15 min. Results Within treatment conditions, sample PCV had no significant effect on cooling. Cooling in ice water was significantly faster than cooling in ice only or transferring the sample to a precooled tube and cooling it on ice. Mean temperature of samples cooled in ice water was significantly lower at 15 min than mean temperatures of those cooled in ice, whether or not the tube was precooled. By 4 min, samples cooled in an ice water bath had reached mean temperatures less than 4 °C (refrigeration temperature), while samples cooled in other conditions remained above 4.0 °C for at least 11 min. For samples with a PCV of 40%, precooling the tube had no significant effect on rate of cooling on ice. For samples with a PCV of 20%, transfer to a precooled tube resulted in a significantly faster rate of cooling than direct placement of the warmed tube onto ice. Discussion Canine EDTA whole blood samples cool most rapidly and to a greater degree when placed in an ice-water bath rather than in ice. Samples stored on ice water can rapidly drop below normal refrigeration temperatures; this should be taken into consideration when using this cooling modality. PMID:27917319

Blood transfusion-acquired hemoglobin C.

PubMed

Suarez, A A; Polski, J M; Grossman, B J; Johnston, M F

1999-07-01

Unexpected and confusing laboratory test results can occur if a blood sample is inadvertently collected following a blood transfusion. A potential for transfusion-acquired hemoglobinopathy exists because heterozygous individuals show no significant abnormalities during the blood donor screening process. Such spurious results are infrequently reported in the medical literature. We report a case of hemoglobin C passively transferred during a red blood cell transfusion. The proper interpretation in our case was assisted by calculations comparing expected hemoglobin C concentration with the measured value. A review of the literature on transfusion-related preanalytic errors is provided.

[Point of Care 2.0: Coagulation Monitoring Using Rotem® Sigma and Teg® 6S].

PubMed

Weber, Christian Friedrich; Zacharowski, Kai

2018-06-01

New-generation methods for point of care based coagulation monitoring enable fully automated viscoelastic analyses for the assessment of particular parts of hemostasis. Contrary to the measuring techniques of former models, the viscoelastic ROTEM ® sigma and TEG ® 6s analyses are performed in single-use test cartridges without time- and personnel-intensive pre-analytical procedures. This review highlights methodical strengths and limitations of the devices and meets concerns associated with their integration in routine clinical practice. Georg Thieme Verlag KG Stuttgart · New York.

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2017-10-01

10 7 4.903 10 8 0.300 3 No - Quit Smoking 75 AR Asbestos, Coal mining, Second-hand smoke Asbestos, Coal mining, Second- hand smoke S0004 Squamous...Cell Carcinoma Stage IIB Y N 1.942 100 75 5 10 7 4.903 10 8 0.300 3 No - Quit Smoking 75 AR Asbestos, Coal mining, Second-hand smoke Asbestos... Coal mining, Second- hand smoke S0006 Adenocarcinoma Stage IB Y N 0.38 80 40 0 2 3 0.310 2 4 No - Quit Smoking 37 None None S0007 Squamous Cell

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2015-10-01

Y N 1.942 20 80 5 10 7 4.903 10 8 0.300 3 No - Quit Smoking 75 AR Asbestos , Coal mining, Second- hand smoke Asbestos , Coal mining, Second...hand smoke S0004 Squamous Cell Carcinoma Stage IIB Y N 1.942 100 75 5 10 7 4.903 10 8 0.300 3 No - Quit Smoking 75 AR Asbestos , Coal mining, Second...hand smoke Asbestos , Coal mining, Second- hand smoke S0006 Adenocarcinoma Stage IB Y N 0.38 80 40 0 2 3 0.310 2 4 No - Quit Smoking 37 None None

The Effect of Pre-Analytical Variability on the Measurement of MRM-MS-Based Mid- to High-Abundance Plasma Protein Biomarkers and a Panel of Cytokines

PubMed Central

Aguilar-Mahecha, Adriana; Kuzyk, Michael A.; Domanski, Dominik; Borchers, Christoph H.; Basik, Mark

2012-01-01

Blood sample processing and handling can have a significant impact on the stability and levels of proteins measured in biomarker studies. Such pre-analytical variability needs to be well understood in the context of the different proteomics platforms available for biomarker discovery and validation. In the present study we evaluated different types of blood collection tubes including the BD P100 tube containing protease inhibitors as well as CTAD tubes, which prevent platelet activation. We studied the effect of different processing protocols as well as delays in tube processing on the levels of 55 mid and high abundance plasma proteins using novel multiple-reaction monitoring-mass spectrometry (MRM-MS) assays as well as 27 low abundance cytokines using a commercially available multiplexed bead-based immunoassay. The use of P100 tubes containing protease inhibitors only conferred proteolytic protection for 4 cytokines and only one MRM-MS-measured peptide. Mid and high abundance proteins measured by MRM are highly stable in plasma left unprocessed for up to six hours although platelet activation can also impact the levels of these proteins. The levels of cytokines were elevated when tubes were centrifuged at cold temperature, while low levels were detected when samples were collected in CTAD tubes. Delays in centrifugation also had an impact on the levels of cytokines measured depending on the type of collection tube used. Our findings can help in the development of guidelines for blood collection and processing for proteomic biomarker studies. PMID:22701622

The effect of pre-analytical variability on the measurement of MRM-MS-based mid- to high-abundance plasma protein biomarkers and a panel of cytokines.

PubMed

Aguilar-Mahecha, Adriana; Kuzyk, Michael A; Domanski, Dominik; Borchers, Christoph H; Basik, Mark

2012-01-01

Blood sample processing and handling can have a significant impact on the stability and levels of proteins measured in biomarker studies. Such pre-analytical variability needs to be well understood in the context of the different proteomics platforms available for biomarker discovery and validation. In the present study we evaluated different types of blood collection tubes including the BD P100 tube containing protease inhibitors as well as CTAD tubes, which prevent platelet activation. We studied the effect of different processing protocols as well as delays in tube processing on the levels of 55 mid and high abundance plasma proteins using novel multiple-reaction monitoring-mass spectrometry (MRM-MS) assays as well as 27 low abundance cytokines using a commercially available multiplexed bead-based immunoassay. The use of P100 tubes containing protease inhibitors only conferred proteolytic protection for 4 cytokines and only one MRM-MS-measured peptide. Mid and high abundance proteins measured by MRM are highly stable in plasma left unprocessed for up to six hours although platelet activation can also impact the levels of these proteins. The levels of cytokines were elevated when tubes were centrifuged at cold temperature, while low levels were detected when samples were collected in CTAD tubes. Delays in centrifugation also had an impact on the levels of cytokines measured depending on the type of collection tube used. Our findings can help in the development of guidelines for blood collection and processing for proteomic biomarker studies.

Clinical biochemistry laboratory rejection rates due to various types of preanalytical errors.

PubMed

Atay, Aysenur; Demir, Leyla; Cuhadar, Serap; Saglam, Gulcan; Unal, Hulya; Aksun, Saliha; Arslan, Banu; Ozkan, Asuman; Sutcu, Recep

2014-01-01

Preanalytical errors, along the process from the beginning of test requests to the admissions of the specimens to the laboratory, cause the rejection of samples. The aim of this study was to better explain the reasons of rejected samples, regarding to their rates in certain test groups in our laboratory. This preliminary study was designed on the rejected samples in one-year period, based on the rates and types of inappropriateness. Test requests and blood samples of clinical chemistry, immunoassay, hematology, glycated hemoglobin, coagulation and erythrocyte sedimentation rate test units were evaluated. Types of inappropriateness were evaluated as follows: improperly labelled samples, hemolysed, clotted specimen, insufficient volume of specimen and total request errors. A total of 5,183,582 test requests from 1,035,743 blood collection tubes were considered. The total rejection rate was 0.65 %. The rejection rate of coagulation group was significantly higher (2.28%) than the other test groups (P < 0.001) including insufficient volume of specimen error rate as 1.38%. Rejection rates of hemolysis, clotted specimen and insufficient volume of sample error were found to be 8%, 24% and 34%, respectively. Total request errors, particularly, for unintelligible requests were 32% of the total for inpatients. The errors were especially attributable to unintelligible requests of inappropriate test requests, improperly labelled samples for inpatients and blood drawing errors especially due to insufficient volume of specimens in a coagulation test group. Further studies should be performed after corrective and preventive actions to detect a possible decrease in rejecting samples.

Validation of cell-based fluorescence assays: practice guidelines from the ICSH and ICCS - part II - preanalytical issues.

PubMed

Davis, Bruce H; Dasgupta, Amar; Kussick, Steven; Han, Jin-Yeong; Estrellado, Annalee

2013-01-01

Flow cytometry and other technologies of cell-based fluorescence assays are as a matter of good laboratory practice required to validate all assays, which when in clinical practice may pass through regulatory review processes using criteria often defined with a soluble analyte in plasma or serum samples in mind. Recently the U.S. Food and Drug Administration (FDA) has entered into a public dialogue in the U.S. regarding their regulatory interest in laboratory developed tests (LDTs) or so-called "home brew" assays performed in clinical laboratories. The absence of well-defined guidelines for validation of cell-based assays using fluorescence detection has thus become a subject of concern for the International Council for Standardization of Haematology (ICSH) and International Clinical Cytometry Society (ICCS). Accordingly, a group of over 40 international experts in the areas of test development, test validation, and clinical practice of a variety of assay types using flow cytometry and/or morphologic image analysis were invited to develop a set of practical guidelines useful to in vitro diagnostic (IVD) innovators, clinical laboratories, regulatory scientists, and laboratory inspectors. The focus of the group was restricted to fluorescence reporter reagents, although some common principles are shared by immunohistochemistry or immunocytochemistry techniques and noted where appropriate. The work product of this two year effort is the content of this special issue of this journal, which is published as 5 separate articles, this being Validation of Cell-based Fluorescence Assays: Practice Guidelines from the ICSH and ICCS - Part II - Preanalytical issues. © 2013 International Clinical Cytometry Society. © 2013 International Clinical Cytometry Society.

Mobile phone exposure influences some erythrocytes parameters in vitro. A novel source of preanalytical variability?

PubMed

Danese, Elisa; Lippi, Giuseppe; Brocco, Giorgio; Montagnana, Martina; Salvagno, Gian Luca

2016-06-01

The effect of radiofrequency exposure on human health and health care equipment is a matter of ongoing debate. This study was planned to investigate the influence of radiofrequency (RF) waves emitted by a commercial mobile phone on red blood cells (RBC) in vitro. The study population consisted of 16 ostensibly healthy volunteers. Two whole blood specimens were collected from each volunteer. One sample was placed in a plastic rack, 1 cm distant from the chassis of a commercial mobile phone which was activated by a remote phone call lasting 30 min. The other blood sample was placed in another plastic rack, but was kept distant from any type of RF source. The main RBC parameters including RBC count, hematocrit (Ht), hemoglobin, mean corpuscular platelet volume (MPV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and RBC distribution width (RDW-CV) were assessed with an Advia 2120. The exposure of whole blood to the mobile phone call significantly increased Ht, hemoglobin, MCV and MCH, whereas the RBC count, MCHC and RDW-CV remained unchanged. A significant correlation was observed between variation of Ht and those of hemoglobin (p=0.008), MCV (p=0.009) or MCH (p=0.037), as well as between hemoglobin and MCV (p=0.048). Increased values were found in 13/16 (81%) samples for both Ht and hemoglobin, 14/16 (88%) samples for MCH and 16/16 (100%) samples for MCV. These results suggest that close mobile phone exposure may be an unappreciated and possibly underestimated cause of preanalytical bias in RBC testing.

Preanalytical stability of maternal serum markers hCGβ and PAPP-A.

PubMed

Veyrat, Béatrice; Tosetti, François; Morin, Jean-François; Moineau, Marie-Pierre; Piedimonte, Andrée; Clément, Patrice; Dreux, Sophie; Muller, Françoise

2017-04-01

Down syndrome maternal serum marker screening is based on a risk calculation including the free β - human chorionic gonadotropin (hCGβ) and pregnancy-associated placenta protein type A (PAPP-A). The aim of this study was to define the pre-analytical conditions of stability of these markers both in whole blood at 15-25 ̊C and, after centrifugation, in serum at 4-8 ̊C. 158 patients were included in the study. Two automated workstations were used for assays, Cobas 8000e602, Roche Diagnostics (58 patients tested) and DELFIAXpress, PerkinElmer (100 patients tested). The stability of markers was studied in whole blood (15-25 ̊C) 2, 4, 6 and 8 hours after sampling and in serum stored after centrifugation at 4-8 ̊C at 24, 72 and 120 hours. Variations were defined by (C T - C 2 )/C 2 , C 2 being the marker concentration at 2 hours and C T the concentration at time T. In whole blood kept for 8 hours at 15-25 ̊C, hCGβ increased by a mean 2.4%, whereas the mean increase of PAPP-A was < 1%. In the serum kept for 5 days at 4-8̊C, the mean increase of hCGβ was 4.2%, with no change in PAPP-A. The impact of these variations on risk calculation is low. In conclusion, maternal serum can be store 8 hours at 15-25̊C in whole blood and 5 days at 4-8̊C after centrifugation and serum separation for Down syndrome maternal serum screening.

The cobas p 630 instrument: a dedicated pre-analytic solution to optimize COBAS® AmpliPrep/COBAS® TaqMan® system workflow and turn-around-time.

PubMed

Vallefuoco, L; Sorrentino, R; Spalletti Cernia, D; Colucci, G; Portella, G

2012-12-01

The cobas p 630, a fully automated pre-analytical instrument for primary tube handling recently introduced to complete the Cobas(®) TaqMan systems portfolio, was evaluated in conjunction with: the COBAS(®) AmpliPrep/COBAS(®) TaqMan HBV Test, v2.0, COBAS(®) AmpliPrep/COBAS(®) TaqMan HCV Test, v1.0 and COBAS(®) AmpliPrep/COBAS(®) TaqMan HIV Test, v2.0. The instrument performance in transferring samples from primary to secondary tubes, its impact in improving COBAS(®) AmpliPrep/COBAS(®) TaqMan workflow and hands-on reduction and the risk of possible cross-contamination were assessed. Samples from 42 HBsAg positive, 42 HCV and 42 HIV antibody (Ab) positive patients as well as 21 healthy blood donors were processed with or without automated primary tubes. HIV, HCV and HBsAg positive samples showed a correlation index of 0.999, 0.987 and of 0.994, respectively. To assess for cross-contamination, high titer HBV DNA positive samples, HCV RNA and HIV RNA positive samples were distributed in the cobas p 630 in alternate tube positions, adjacent to negative control samples within the same rack. None of the healthy donor samples showed any reactivity. Based on these results, the cobas p 630 can improve workflow and sample tracing in laboratories performing molecular tests, and reduce turnaround time, errors, and risks. Copyright © 2012 Elsevier B.V. All rights reserved.

External quality assessment of urine particle identification: a Northern European experience.

PubMed

Kouri, Timo T; Makkonen, Pirjo

2015-11-01

External quality assessment (EQA) schemes for urinalysis have been provided by Labquality Ltd, the publicly owned EQA service provider in Finland, since the 1980s. In 2014, the scheme on urine particle identification had 329 participating laboratories, out of which 60% from 19 countries were outside Finland. Each of the four annual web-based rounds were distributed with four Sternheimer-stained images from a single patient sample, as viewed both by bright-field and phase-contrast optics. Participants reported classified categories either at the basic or at the advanced level. Participating laboratories received assessment of their analytical performance as compared to their peers, including reflections from clinical data and preanalytical detail of the specimen. In general, reporting of basic urine particles succeeded in the eight schemes during the years 2013-2014 as follows: red blood cells 82%-92%, white blood cells 82%-97%, squamous epithelial cells 92%-98%, casts 84%-94%, and small epithelial cells 73%-83% (minimum and maximum of expected or accepted reports). This basic level of differentiation is used in routine laboratory reports, or as verification of results produced by automated instruments. Considerable effort is needed to standardise national procedures and reporting formats, in order to improve the shown figures internationally. Future technologies may help to alleviate limitations created by single digital images. Despite improvements, degenerating cells and casts always exhibit intermediate forms creating disputable classifications. That is why assessment of performance should encompass justified acceptable categories into the assessed outcomes. Preanalytical and clinical detail provide essential added value to morphological findings.

Laboratory testing of extravascular body fluids in Croatia: a survey of the Working group for extravascular body fluids of the Croatian Society of Medical Biochemistry and Laboratory Medicine

PubMed Central

Kopcinovic, Lara Milevoj; Vogrinc, Zeljka; Kocijan, Irena; Culej, Jelena; Aralica, Merica; Jokic, Anja; Antoncic, Dragana; Bozovic, Marija

2016-01-01

Introduction We hypothesized that extravascular body fluid (EBF) analysis in Croatia is not harmonized and aimed to investigate preanalytical, analytical and postanalytical procedures used in EBF analysis in order to identify key aspects that should be addressed in future harmonization attempts. Materials and methods An anonymous online survey created to explore laboratory testing of EBF was sent to secondary, tertiary and private health care Medical Biochemistry Laboratories (MBLs) in Croatia. Statements were designed to address preanalytical, analytical and postanalytical procedures of cerebrospinal, pleural, peritoneal (ascites), pericardial, seminal, synovial, amniotic fluid and sweat. Participants were asked to declare the strength of agreement with proposed statements using a Likert scale. Mean scores for corresponding separate statements divided according to health care setting were calculated and compared. Results The survey response rate was 0.64 (58 / 90). None of the participating private MBLs declared to analyse EBF. We report a mean score of 3.45 obtained for all statements evaluated. Deviations from desirable procedures were demonstrated in all EBF testing phases. Minor differences in procedures used for EBF analysis comparing secondary and tertiary health care MBLs were found. The lowest scores were obtained for statements regarding quality control procedures in EBF analysis, participation in proficiency testing programmes and provision of interpretative comments on EBF’s test reports. Conclusions Although good laboratory EBF practice is present in Croatia, procedures for EBF analysis should be further harmonized to improve the quality of EBF testing and patient safety. PMID:27812307

Blood sample collection and patient identification demand improvement: a questionnaire study of preanalytical practices in hospital wards and laboratories.

PubMed

Wallin, Olof; Söderberg, Johan; Van Guelpen, Bethany; Stenlund, Hans; Grankvist, Kjell; Brulin, Christine

2010-09-01

Scand J Caring Sci; 2010; 24; 581-591 
 Blood sample collection and patient identification demand improvement: a questionnaire study of preanalytical practices in hospital wards and laboratories   Most errors in venous blood testing result from human mistakes occurring before the sample reach the laboratory.   To survey venous blood sampling (VBS) practices in hospital wards and to compare practices with hospital laboratories.   Staff in two hospitals (all wards) and two hospital laboratories (314 respondents, response rate 94%), completed a questionnaire addressing issues relevant to the collection of venous blood samples for clinical chemistry testing.   The findings suggest that instructions for patient identification and the collection of venous blood samples were not always followed. For example, 79% of the respondents reported the undesirable practice (UDP) of not always using wristbands for patient identification. Similarly, 87% of the respondents noted the UDP of removing venous stasis after the sampling is finished. Compared with the ward staff, a significantly higher proportion of the laboratory staff reported desirable practices regarding the collection of venous blood samples. Neither education nor the existence of established sampling routines was clearly associated with VBS practices among the ward staff.   The results of this study, the first of its kind, suggest that a clinically important risk of error is associated with VBS in the surveyed wards. Most important is the risk of misidentification of patients. Quality improvement of blood sample collection is clearly needed, particularly in hospital wards. © 2009 The Authors. Journal compilation © 2009 Nordic College of Caring Science.

Impact of Altering Various Image Parameters on Human Epidermal Growth Factor Receptor 2 Image Analysis Data Quality.

PubMed

Pantanowitz, Liron; Liu, Chi; Huang, Yue; Guo, Huazhang; Rohde, Gustavo K

2017-01-01

The quality of data obtained from image analysis can be directly affected by several preanalytical (e.g., staining, image acquisition), analytical (e.g., algorithm, region of interest [ROI]), and postanalytical (e.g., computer processing) variables. Whole-slide scanners generate digital images that may vary depending on the type of scanner and device settings. Our goal was to evaluate the impact of altering brightness, contrast, compression, and blurring on image analysis data quality. Slides from 55 patients with invasive breast carcinoma were digitized to include a spectrum of human epidermal growth factor receptor 2 (HER2) scores analyzed with Visiopharm (30 cases with score 0, 10 with 1+, 5 with 2+, and 10 with 3+). For all images, an ROI was selected and four parameters (brightness, contrast, JPEG2000 compression, out-of-focus blurring) then serially adjusted. HER2 scores were obtained for each altered image. HER2 scores decreased with increased illumination, higher compression ratios, and increased blurring. HER2 scores increased with greater contrast. Cases with HER2 score 0 were least affected by image adjustments. This experiment shows that variations in image brightness, contrast, compression, and blurring can have major influences on image analysis results. Such changes can result in under- or over-scoring with image algorithms. Standardization of image analysis is recommended to minimize the undesirable impact such variations may have on data output.

Microfluidics enables multiplex evaluation of the same cells for further studies.

PubMed

Mojica, W D; Oh, K W; Lee, H; Furlani, E P; Sykes, D; Sands, A M

2016-08-01

The continuous discovery of biomarkers and their evolving use for the diagnosis and guidance of therapy for patients with cancer has increased awareness of the need to triage biospecimens properly. On occasion, cytology samples are the only type of biospecimen available for analysis. Often, the current approach for these latter specimens is cytopathology-centric, with cells limited to examination by bright field microscopy. When specimens are paucicellular, there is often insufficient material for ancillary testing. Therefore, a need exists to develop an alternative approach that allows for the multiplexed analysis of cells when they are limited in number. In recent previous publications, we demonstrated that clinically derived cells from tissue are suitable for evaluation in a microfluidic device. In our current endeavour, we seek to expand upon those findings and determine if those same cells can be recovered for further analysis. A microfluidic channel was designed, fabricated and tested using cytology specimens generated from tissue specimens. The cytological features of the cells tested were examined prior to entering the channel; they were then compared to similar cells while in the channel, and upon recovery from the channel. Recovery of DNA and proteins were also tested. The morphology of the tested cells was not compromised in either the channel or upon recovery. More importantly, the integrity of the cells remained intact, with the recovery of proteins and high molecular weight DNA possible. We developed and tested an alternative approach to the processing of cytopathology specimens that enables multiplexed evaluation. Using microfluidics, cytological examination of biopecimens can be performed, but in contrast to existing approaches, the same cells examined can be recovered for downstream analysis. © 2015 John Wiley & Sons Ltd.

The "North German Tumor Bank of Colorectal Cancer": status report after the first 2 years of support by the German Cancer Aid Foundation.

PubMed

Oberländer, Martina; Linnebacher, Michael; König, Alexandra; Bogoevska, Valentina; Brodersen, Christiane; Kaatz, Regina; Krohn, Mathias; Hackmann, Michael; Ingenerf, Josef; Christoph, Jan; Mate, Sebastian; Prokosch, Hans-Ulrich; Yekebas, Emre F; Thorns, Christoph; Büning, Jürgen; Prall, Friedrich; Uhlig, Ria; Roblick, Uwe J; Izbicki, Jakob R; Klar, Ernst; Bruch, Hans-Peter; Vollmar, Brigitte; Habermann, Jens K

2013-02-01

Research projects and clinical trials strongly rely on high-quality biospecimens which are provided by biobanks. Since differences in sample processing and storage can strongly affect the outcome of such studies, standardization between biobanks is necessary to guarantee reliable results of large, multicenter studies. The German Cancer Aid Foundation (Deutsche Krebshilfe e.V.) has therefore initiated the priority program "tumor tissue banks" in 2010 by funding four biobank networks focusing on central nervous system tumors, melanomas, breast carcinomas, and colorectal carcinomas. The latter one, the North German Tumor Bank of Colorectal Cancer (ColoNet) is managed by surgeons, pathologists, gastroenterologists, oncologists, scientists, and medical computer scientists. The ColoNet consortium has developed and harmonized standard operating procedures concerning all biobanking aspects. Crucial steps for quality assurance have been implemented and resulted in certification according to DIN EN ISO 9001. A further achievement is the construction of a web-based database for exploring available samples. In addition, common scientific projects have been initiated. Thus, ColoNet's repository will be used for research projects in order to improve early diagnosis, therapy, follow-up, and prognosis of colorectal cancer patients. Apart from the routine sample storage at -170 °C, the tumor banks' unique characteristic is the participation of outpatient clinics and private practices to further expand the sample and clinical data collection. The first 2 years of funding by the German Cancer Aid Foundation have already led to a closer scientific connection between the participating institutions and to a substantial collection of biospecimens obtained under highly standardized conditions.

A widefield fluorescence microscope with a linear image sensor for image cytometry of biospecimens: Considerations for image quality optimization

NASA Astrophysics Data System (ADS)

Hutcheson, Joshua A.; Majid, Aneeka A.; Powless, Amy J.; Muldoon, Timothy J.

2015-09-01

Linear image sensors have been widely used in numerous research and industry applications to provide continuous imaging of moving objects. Here, we present a widefield fluorescence microscope with a linear image sensor used to image translating objects for image cytometry. First, a calibration curve was characterized for a custom microfluidic chamber over a span of volumetric pump rates. Image data were also acquired using 15 μm fluorescent polystyrene spheres on a slide with a motorized translation stage in order to match linear translation speed with line exposure periods to preserve the image aspect ratio. Aspect ratios were then calculated after imaging to ensure quality control of image data. Fluorescent beads were imaged in suspension flowing through the microfluidics chamber being pumped by a mechanical syringe pump at 16 μl min-1 with a line exposure period of 150 μs. The line period was selected to acquire images of fluorescent beads with a 40 dB signal-to-background ratio. A motorized translation stage was then used to transport conventional glass slides of stained cellular biospecimens. Whole blood collected from healthy volunteers was stained with 0.02% (w/v) proflavine hemisulfate was imaged to highlight leukocyte morphology with a 1.56 mm × 1.28 mm field of view (1540 ms total acquisition time). Oral squamous cells were also collected from healthy volunteers and stained with 0.01% (w/v) proflavine hemisulfate to demonstrate quantifiable subcellular features and an average nuclear to cytoplasmic ratio of 0.03 (n = 75), with a resolution of 0.31 μm pixels-1.

Inhibition in a microgravity environment of the recovery of Escherichia coli cells damaged by heavy ion beams during the NASDA ISS phase I program of NASA Shuttle/Mir mission no. 6.

PubMed

Harada, K; Sugahara, T; Ohnishi, T; Ozaki, Y; Obiya, Y; Miki, S; Miki, T; Imamura, M; Kobayashi, Y; Watanabe, H; Akashi, M; Furusawa, Y; Mizuma, N; Yamanaka, H; Ohashi, E; Yamaoka, C; Yajima, M; Fukui, M; Nakano, T; Takahashi, S; Amano, T; Sekikawa, K; Yanagawa, K; Nagaoka, S

1998-05-01

We participated in a space experiment, part of the National Space Development Agency of Japan (NASDA) Phase I Space Radiation Environment Measurement Program, conducted during the National Aeronautics and Space Administration (NASA) Shuttle/Mir Mission No. 6 (S/MM-6) project. The aim of our study was to investigate the effects of microgravity on the DNA repair processes of living organisms in the in orbit. Heavy ion beam radiation- or ç-irradiation-damaged biological samples of Escherichia coli and the radioresistant bacterium Deinococcus radiodurans were prepared and placed in a biospecimen box, which was loaded into the RRMD III sensor unit of the Space Shuttle. Two identical sets of samples were left in the Spacehab's Payload Processing Facility (SPPF) in Florida, USA, as a control. (flight No. STS-84) was launched from NASA John F. Kennedy Space Center (KSC) in Florida, USA, on May 15, 1997. The mission duration was 9.22 days. An astronaut activated the biological samples in the biospecimen box in the Spacehab during orbit in order to start repair of the DNA damaged by heavy ion beams or ç-irradiation and the samples were incubated for 19 h 35 min at about 22ûC, the cabin temperature. The control specimens in the SPPF were subjected to the same treatment under terrestrial gravity. After returned to earth, we investigated cell recovery by comparing the repair of the radiation-damaged DNA of E. coli and D. radiodurans in the microgravity environment in space with that on Earth. The results indicated that the DNA repair process of E. coli, but not of D. radiodurans, cells was inhibited in a microgravity environment.

The biobank for the molecular classification of kidney disease: research translation and precision medicine in nephrology.

PubMed

Muruve, Daniel A; Mann, Michelle C; Chapman, Kevin; Wong, Josee F; Ravani, Pietro; Page, Stacey A; Benediktsson, Hallgrimur

2017-07-26

Advances in technology and the ability to interrogate disease pathogenesis using systems biology approaches are exploding. As exemplified by the substantial progress in the personalized diagnosis and treatment of cancer, the application of systems biology to enable precision medicine in other disciplines such as Nephrology is well underway. Infrastructure that permits the integration of clinical data, patient biospecimens and advanced technologies is required for institutions to contribute to, and benefit from research in molecular disease classification and to devise specific and patient-oriented treatments. We describe the establishment of the Biobank for the Molecular Classification of Kidney Disease (BMCKD) at the University of Calgary, Alberta, Canada. The BMCKD consists of a fully equipped wet laboratory, an information technology infrastructure, and a formal operational, ethical and legal framework for banking human biospecimens and storing clinical data. The BMCKD first consolidated a large retrospective cohort of kidney biopsy specimens to create a population-based renal pathology database and tissue inventory of glomerular and other kidney diseases. The BMCKD will continue to prospectively bank all kidney biopsies performed in Southern Alberta. The BMCKD is equipped to perform molecular, clinical and epidemiologic studies in renal pathology. The BMCKD also developed formal biobanking procedures for human specimens such as blood, urine and nucleic acids collected for basic and clinical research studies or for advanced diagnostic technologies in clinical care. The BMCKD is guided by standard operating procedures, an ethics framework and legal agreements with stakeholders that include researchers, data custodians and patients. The design and structure of the BMCKD permits its inclusion in a wide variety of research and clinical activities. The BMCKD is a core multidisciplinary facility that will bridge basic and clinical research and integrate precision medicine into renal pathology and nephrology.

Effect of multiple cycles of freeze-thawing on the RNA quality of lung cancer tissues.

PubMed

Yu, Keke; Xing, Jie; Zhang, Jie; Zhao, Ruiying; Zhang, Ye; Zhao, Lanxiang

2017-09-01

RNA degradation is a major problem in tissue banking. We explored the effect of thawing flash-frozen biospecimens on the quality and integrity of RNA for genetic testing as well as for other cancer research studies. The histological quality of the frozen tumor sections was evaluated by using hematoxylin and eosin staining. RNA extraction from 60 lung cancer tissue samples subjected to various freeze/thaw cycles was performed using the RNeasy Plus isolation kit. RNA integrity was assessed by using an Agilent bioanalyzer to obtain RNA integrity numbers (RIN). Furthermore, RNA from different groups was used for fluorescence Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK) fusion gene mutation to verify whether it can be used for research or clinical testing. Highly variable RIN values were observed among the samples, which showed no correlation with the number of freeze/thaw cycles conducted. However, after 3 freeze/thaw cycles (each thaw event lasted for 10 min), an increasing number of changes in peak intensity in RINs were observed. After 5 freeze/thaw cycles, RNA integrity decreased to approximately 35%. After 3 freeze/thaw cycles, the RNA could still be used for RT-PCR analysis of EML4-ALK fusion gene mutations; whereas those subjected to 5 freeze/thaw cycles could not. Limited (<3) freeze/thaw cycles did not adversely affect the quality of RNA extracted from tumor tissues and subsequent RT-PCR analysis. Our data could be utilized in the establishment of a standardized procedure for tissue biospecimen collection and storage.

A widefield fluorescence microscope with a linear image sensor for image cytometry of biospecimens: Considerations for image quality optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hutcheson, Joshua A.; Majid, Aneeka A.; Powless, Amy J.

Linear image sensors have been widely used in numerous research and industry applications to provide continuous imaging of moving objects. Here, we present a widefield fluorescence microscope with a linear image sensor used to image translating objects for image cytometry. First, a calibration curve was characterized for a custom microfluidic chamber over a span of volumetric pump rates. Image data were also acquired using 15 μm fluorescent polystyrene spheres on a slide with a motorized translation stage in order to match linear translation speed with line exposure periods to preserve the image aspect ratio. Aspect ratios were then calculated aftermore » imaging to ensure quality control of image data. Fluorescent beads were imaged in suspension flowing through the microfluidics chamber being pumped by a mechanical syringe pump at 16 μl min{sup −1} with a line exposure period of 150 μs. The line period was selected to acquire images of fluorescent beads with a 40 dB signal-to-background ratio. A motorized translation stage was then used to transport conventional glass slides of stained cellular biospecimens. Whole blood collected from healthy volunteers was stained with 0.02% (w/v) proflavine hemisulfate was imaged to highlight leukocyte morphology with a 1.56 mm × 1.28 mm field of view (1540 ms total acquisition time). Oral squamous cells were also collected from healthy volunteers and stained with 0.01% (w/v) proflavine hemisulfate to demonstrate quantifiable subcellular features and an average nuclear to cytoplasmic ratio of 0.03 (n = 75), with a resolution of 0.31 μm pixels{sup −1}.« less

Cryopreservation of Viable Human Lung Tissue for Versatile Post-thaw Analyses and Culture

PubMed Central

Baatz, John E.; Newton, Danforth A.; Riemer, Ellen C.; Denlinger, Chadrick E.; Jones, E. Ellen; Drake, Richard R.; Spyropoulos, Demetri D.

2018-01-01

Clinical trials are currently used to test therapeutic efficacies for lung cancer, infections and diseases. Animal models are also used as surrogates for human disease. Both approaches are expensive and time-consuming. The utility of human biospecimens as models is limited by specialized tissue processing methods that preserve subclasses of analytes (e.g. RNA, protein, morphology) at the expense of others. We present a rapid and reproducible method for the cryopreservation of viable lung tissue from patients undergoing lobectomy or transplant. This method involves the pseudo-diaphragmatic expansion of pieces of fresh lung tissue with cryoprotectant formulation (pseudo-diaphragmatic expansion-cryoprotectant perfusion or PDX-CP) followed by controlled-rate freezing in cryovials. Expansion-perfusion rates, volumes and cryoprotectant formulation were optimized to maintain tissue architecture, decrease crystal formation and increase long-term cell viability. Rates of expansion of 4 cc/min or less and volumes ranging from 0.8–1.2 × tissue volume were well-tolerated by lung tissue obtained from patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis, showing minimal differences compared to standard histopathology. Morphology was greatly improved by the PDX-CP procedure compared to simple fixation. Fresh versus post-thawed lung tissue showed minimal differences in histology, RNA integrity numbers and post-translational modified protein integrity (2-dimensional differential gel electrophoresis). It was possible to derive numerous cell types, including alveolar epithelial cells, fibroblasts and stem cells, from the tissue for at least three months after cryopreservation. This new method should provide a uniform, cost-effective approach to the banking of biospecimens, with versatility to be amenable to any post-acquisition process applicable to fresh tissue samples. PMID:24982205

Genetic Basis of Autoantibody Positive and Negative Rheumatoid Arthritis Risk in a Multi-ethnic Cohort Derived from Electronic Health Records

PubMed Central

Kurreeman, Fina; Liao, Katherine; Chibnik, Lori; Hickey, Brendan; Stahl, Eli; Gainer, Vivian; Li, Gang; Bry, Lynn; Mahan, Scott; Ardlie, Kristin; Thomson, Brian; Szolovits, Peter; Churchill, Susanne; Murphy, Shawn N.; Cai, Tianxi; Raychaudhuri, Soumya; Kohane, Isaac; Karlson, Elizabeth; Plenge, Robert M.

2011-01-01

Discovering and following up on genetic associations with complex phenotypes require large patient cohorts. This is particularly true for patient cohorts of diverse ancestry and clinically relevant subsets of disease. The ability to mine the electronic health records (EHRs) of patients followed as part of routine clinical care provides a potential opportunity to efficiently identify affected cases and unaffected controls for appropriate-sized genetic studies. Here, we demonstrate proof-of-concept that it is possible to use EHR data linked with biospecimens to establish a multi-ethnic case-control cohort for genetic research of a complex disease, rheumatoid arthritis (RA). In 1,515 EHR-derived RA cases and 1,480 controls matched for both genetic ancestry and disease-specific autoantibodies (anti-citrullinated protein antibodies [ACPA]), we demonstrate that the odds ratios and aggregate genetic risk score (GRS) of known RA risk alleles measured in individuals of European ancestry within our EHR cohort are nearly identical to those derived from a genome-wide association study (GWAS) of 5,539 autoantibody-positive RA cases and 20,169 controls. We extend this approach to other ethnic groups and identify a large overlap in the GRS among individuals of European, African, East Asian, and Hispanic ancestry. We also demonstrate that the distribution of a GRS based on 28 non-HLA risk alleles in ACPA+ cases partially overlaps with ACPA- subgroup of RA cases. Our study demonstrates that the genetic basis of rheumatoid arthritis risk is similar among cases of diverse ancestry divided into subsets based on ACPA status and emphasizes the utility of linking EHR clinical data with biospecimens for genetic studies. PMID:21211616

Microplates in liquid chromatography--new solution in clinical research? A review.

PubMed

Krcmova, Lenka; Solichova, Dagmar; Solich, Petr

2013-10-15

Microplates are routinely used in Radio- or Immuno-assays. Recently, microplates have found use not only in analytical but also in the pre-analytical phase in bioanalyses (sample storage, sample preparation). New connection of this technology to liquid chromatography could be economical, fast and simple solution for many routine laboratories handling large sequences of biological samples. This review summarises the application of microplates in bioanalytical laboratories. Different types of sorbents, materials and shapes of microplates are discussed, and the main advantages and disadvantages of microplates used in clinical research are presented. Copyright © 2013 Elsevier B.V. All rights reserved.

[Management of pre-analytical nonconformities].

PubMed

Berkane, Z; Dhondt, J L; Drouillard, I; Flourié, F; Giannoli, J M; Houlbert, C; Surgat, P; Szymanowicz, A

2010-12-01

The main nonconformities enumerated to facilitate consensual codification. In each case, an action is defined: refusal to realize the examination with request of a new sample, request of information or correction, results cancellation, nurse or physician information. A traceability of the curative, corrective and preventive actions is needed. Then, methodology and indicators are proposed to assess nonconformity and to follow the quality improvements. The laboratory information system can be used instead of dedicated software. Tools for the follow-up of nonconformities scores are proposed. Finally, we propose an organization and some tools allowing the management and control of the nonconformities occurring during the pre-examination phase.

[Blood sampling using "dried blood spot": a clinical biology revolution underway?].

PubMed

Hirtz, Christophe; Lehmann, Sylvain

2015-01-01

Blood testing using the dried blood spot (DBS) is used since the 1960s in clinical analysis, mainly within the framework of the neonatal screening (Guthrie test). Since then numerous analytes such as nucleic acids, small molecules or lipids, were successfully measured on the DBS. While this pre-analytical method represents an interesting alternative to classic blood sampling, its use in routine is still limited. We review here the different clinical applications of the blood sampling on DBS and estimate its future place, supported by the new methods of analysis as the LC-MS mass spectrometry.

Nursing and genetic biobanks.

PubMed

Sanner, Jennifer E; Yu, Erica; Udtha, Malini; Williams, Pamela Holtzclaw

2013-12-01

Biobanks function as vital components in genetic research, which often requires large disease-based or population-based biospecimens and clinical data to study complex or rare diseases. Genetic biobanks aim to provide resources for translational research focusing on rapidly moving scientific findings from the laboratory into health care practice. The nursing profession must evolve as genetic biobanking practices advance. Nursing involvement in genetic biobanking practices comes with a distinct set of educational, ethical, and practice competencies. In response to these growing competency standards, nursing science developed a conceptual framework and continues to study ethical considerations to guide genetic biobanking initiatives. Copyright © 2013 Elsevier Inc. All rights reserved.

Collaboration to Accelerate Proteogenomics Cancer Care: The Department of Veterans Affairs, Department of Defense, and the National Cancer Institute's Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) Network.

PubMed

Fiore, L D; Rodriguez, H; Shriver, C D

2017-05-01

A tri-federal initiative arising out of the Cancer Moonshot has resulted in the formation of a program to utilize advanced genomic and proteomic expression platforms on high-quality human biospecimens in near-real-time in order to identify potentially actionable therapeutic molecular targets, study the relationship of molecular findings to cancer treatment outcomes, and accelerate novel clinical trials with biomarkers of prognostic and predictive value. © 2017 Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

The Congenital Heart Disease Genetic Network Study: rationale, design, and early results.

PubMed

Gelb, Bruce; Brueckner, Martina; Chung, Wendy; Goldmuntz, Elizabeth; Kaltman, Jonathan; Kaski, Juan Pablo; Kim, Richard; Kline, Jennie; Mercer-Rosa, Laura; Porter, George; Roberts, Amy; Rosenberg, Ellen; Seiden, Howard; Seidman, Christine; Sleeper, Lynn; Tennstedt, Sharon; Kaltman, Jonathan; Schramm, Charlene; Burns, Kristin; Pearson, Gail; Rosenberg, Ellen

2013-02-15

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community's use of Pediatric Cardiac Genomics Consortium resources is welcome.

Dopamine receptor gene d4 polymorphisms and early sexual onset: gender and environmental moderation in a sample of african-american youth.

PubMed

Kogan, Steven M; Lei, Man-Kit; Beach, Steven R H; Brody, Gene H; Windle, Michael; Lee, Sunbok; MacKillop, James; Chen, Yi-Fu

2014-08-01

Early sexual onset and its consequences disproportionately affect African-American youth, particularly male youth. The dopamine receptor D4 gene (DRD4) has been linked to sexual activity and other forms of appetitive behavior, particularly for male youth and in combination with environmental factors (gene × environment [G × E] effects). The differential susceptibility perspective suggests that DRD4 may exert this effect by amplifying the effects of both positive and negative environments. We hypothesized that DRD4 status would amplify the influence of both positive and negative neighborhood environments on early sexual onset among male, but not female, African-Americans. Hypotheses were tested with self-report, biospecimen, and census data from five prospective studies of male and female African-American youth in rural Georgia communities, N = 1,677. Early sexual onset was defined as intercourse before age 14. No significant G × E findings emerged for female youth. Male youth with a DRD4 long allele were more likely than those with two DRD4 short alleles to report early sexual onset in negative community environments and not to report early onset in positive community environments. Dopaminergic regulation of adolescent sexual behaviors may operate differently by gender. DRD4 operated as an environmental amplification rather than a vulnerability factor. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

The Congenital Heart Disease Genetic Network Study

PubMed Central

2013-01-01

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community’s use of Pediatric Cardiac Genomics Consortium resources is welcome. PMID:23410879

Aflatoxin exposure during the first 36 months of life was not associated with impaired growth in Nepalese children: An extension of the MAL-ED study

PubMed Central

Hsu, Hui-Husan; Chandyo, Ram Krishna; Shrestha, Binob; Bodhidatta, Ladaporn; Tu, Yu-Kang; Gong, Yun-Yun; Egner, Patricia A.; Ulak, Manjeswori; Groopman, John D.; Wu, Felicia

2017-01-01

Exposure to aflatoxin, a mycotoxin common in many foods, has been associated with child growth impairment in sub-Saharan Africa. To improve our understanding of growth impairment in relation to aflatoxin and other risk factors, we assessed biospecimens collected in Nepalese children at 15, 24, and 36 months of age for aflatoxin exposure. Children (N = 85) enrolled in the Bhaktapur, Nepal MAL-ED study encompassed the cohort analysed in this study. Exposure was assessed through a plasma biomarker of aflatoxin exposure: the AFB1-lysine adduct. The aflatoxin exposures in the study participants were compared to anthropometrics at each time period (length-for-age [LAZ], weight-for-age [WAZ], and weight-for-length [WLZ] z-scores), growth trajectories over time, age, and breastfeeding status. Results demonstrated chronic aflatoxin exposure in this cohort of children, with a geometric mean of 3.62 pg AFB1-lysine/mg albumin. However, the chronic aflatoxin exposure in this cohort was not significantly associated with anthropometric z-scores, growth trajectories, age, or feeding status, based on the available time points to assess aflatoxin exposure. Low mean levels of aflatoxin exposure and infrequent occurrence of stunting, wasting, or underweight z-score values in this cohort are possible contributing factors to a lack of evidence for an association. Further research is needed to examine whether a threshold dose of aflatoxin exists that could induce child growth impairment. PMID:28212415

Pitfalls in lung cancer molecular pathology: how to limit them in routine practice?

PubMed

Ilie, M; Hofman, P

2012-01-01

New treatment options in advanced non-small cell lung carcinoma (NSCLC) targeting activating epidermal growth factor receptor (EGFR) gene mutations and other genetic alterations demonstrated the clinical significance of the molecular features of specific subsets of tumors. Therefore, the development of personalized medicine has stimulated the routine integration into pathology departments of somatic mutation testing. However, clinical mutation testing must be optimized and standardized with regard to histological profile, type of samples, pre-analytical steps, methodology and result reporting. Routine molecular testing in NSCLC is currently moving beyond EGFR mutational analysis. Recent progress of targeted therapies will require molecular testing for a wide panel of mutations for a personalized molecular diagnosis. As a consequence, efficient testing of multiple molecular abnormalities is an urgent requirement in thoracic oncology. Moreover, increasingly limited tumor sample becomes a major challenge for molecular pathology. Continuous efforts should be made for safe, effective and specific molecular analyses. This must be based on close collaboration between the departments involved in the management of lung cancer. In this review we explored the practical issues and pitfalls surrounding the routine implementation of molecular testing in NSCLC in a pathology laboratory.

Update on HER2 testing for breast and upper gastrointestinal tract cancers.

PubMed

Ross, Jeffrey S

2011-06-01

With the regulatory approvals in Europe and the USA of trastuzumab-based anti-HER2 targeted therapy for upper gastrointestinal cancers in 2010, HER2 testing has now become universal for newly diagnosed cases of both breast cancer and adenocarcinomas of esophagus, stomach and gastroesophageal origin. In the 12 years or more since the approval of trastuzumab for breast cancer, general refinements in approaches to HER2 testing, including a greater understanding of the implications of preanalytic factors impacting the test results and the application of standardization of reporting of HER2 test results, have taken place. There has also been continuing development in breast cancer with the introduction of new HER2 tests, including non-FISH tests, dimerization assays, phosphorylated HER2 receptor tests, mRNA-based tests, HER2 gene sequencing tests and the application of HER2 testing to circulating tumor cells. Most recently, the introduction of HER2 testing for upper gastrointentinal malignancies has emphasized the need for performing and interpreting slide-based assays in a manner unique to these specimens and not to apply the breast cancer testing protocols to esophageal and gastric adenocarcinomas.

Mass Spectrometric Methodologies for Investigating the Metabolic Signatures of Parkinson's Disease: Current Progress and Future Perspectives.

PubMed

Gill, Emily L; Koelmel, Jeremy P; Yost, Richard A; Okun, Michael S; Vedam-Mai, Vinata; Garrett, Timothy J

2018-03-06

Parkinson's disease (PD) is a neurodegenerative disorder resulting from the loss of dopaminergic neurons of the substantia nigra as well as degeneration of motor and nonmotor basal ganglia circuitries. Typically known for classical motor deficits (tremor, rigidity, bradykinesia), early stages of the disease are associated with a large nonmotor component (depression, anxiety, apathy, etc.). Currently, there are no definitive biomarkers of PD, and the measurement of dopamine metabolites does not allow for detection of prodromal PD nor does it aid in long-term monitoring of disease progression. Given that PD is increasingly recognized as complex and heterogeneous, involving several neurotransmitters and proteins, it is of importance that we advance interdisciplinary studies to further our knowledge of the molecular and cellular pathways that are affected in PD. This approach will possibly yield useful biomarkers for early diagnosis and may assist in the development of disease-modifying therapies. Here, we discuss preanalytical factors associated with metabolomics studies, summarize current mass spectrometric methodologies used to evaluate the metabolic signature of PD, and provide future perspectives of the rapidly developing field of MS in the context of PD.

Ischemic time impacts biological integrity of phospho-proteins in PI3K/Akt, Erk/MAPK, and p38 MAPK signaling networks.

PubMed

Holzer, Timothy R; Fulford, Angie D; Arkins, Austin M; Grondin, Janet M; Mundy, Christopher W; Nasir, Aejaz; Schade, Andrew E

2011-06-01

Post-translational modifications of proteins, such as phosphorylation, are labile events dynamically regulated by opposing kinase and phosphatase activities. Preanalytical factors, such as ischemic time before fixation, affect these activities and can have a significant impact on the ability to elucidate signaling pathways in tissue. Immunohistochemical analysis of phosphorylated proteins involved in PI3K/Akt, Erk/MAPK, and p38 MAPK signaling networks was performed in human cell line xenografts from lung, brain, ovary, and prostate tumors. In order to replicate real-world practices, the tissues were subjected to ischemic times of 0 (baseline), 1, 4, and 24 hours before fixation in formalin. Two key concepts emerge from this analysis: (1) the stability of different phospho-epitopes within a given tumor type is variable (e.g. phospho-PRAS40 is more labile than phospho-S6 ribosomal protein) and (2) the stability of a given phospho-epitope (e.g. phospho-MAPKAPK2) varies significantly across different tumor types. These results highlight the importance of proper tissue acquisition and rapid fixation to preserve the biological integrity of signal transduction pathways that may guide therapeutic decision making.

Rapid differentiation of cocci/mixed bacteria from rods in voided urine culture of women with uncomplicated urinary tract infections.

PubMed

Yang, Chun-Chun; Yang, Stephen Shei-Dei; Hung, Hui-Ching; Chiang, I-Ni; Peng, Chiung-Hui; Chang, Shang-Jen

2017-09-01

To evaluate the ability of laser flow cytometry to predict cocci/mixed growth in the pre-analytical phase of urine specimens. We retrospectively reviewed urine samples from women with uncomplicated urinary tract infections from urologic clinics for study. Urine analyses were performed with laser flow cytometry (UF1000i, Sysmex, Kobe, Japan) and then diagrams were generated (forward scatter vs. fluorescent light scatter). Each specimen (bacteria count >357 BACT/μL) was classified as either cocci bacteria or rods/mixed growth according to the diagrams. Standard urine cultures were performed, and the agreement between cultures and the UF1000i interpretations was analyzed with kappa statistics. Finally, 491 specimens met the criteria for analysis. Among the 376 specimens with single bacteria growth, there were 26 gram-positive cocci (13 Streptococci spp., 7 Staphylococci spp., 6 Enterococci spp.), 1 gram-positive rods (Corynebacterium spp.), and 349 gram-negative rods (273 Escherichia coli, 33 Klebsiella spp., 29 Proteus spp., 6 Citrobacter spp., 4 Enterobacter spp., 3 Pseudomonas spp., and 1 Providencia spp.). There were 115 specimens with two bacteria species or more that were regarded as mixed growth. Agreement of rods or cocci/mixed growth between the laser flow cytometry and urine cultures yielded a kappa value of 0.58. The positive and negative predictive rate of the UF1000i for cocci/mixed growth in voided urine culture was 81.8% and 84.7%, respectively. Through laser flow cytometry, we can predict growth of cocci/mixed growth in the pre-analytical phase of urine culture, thus avoiding unnecessary urine culture and waiting time. © 2016 Wiley Periodicals, Inc.

Setting up a wide panel of patient-derived tumor xenografts of non-small cell lung cancer by improving the preanalytical steps.

PubMed

Ilie, Marius; Nunes, Manoel; Blot, Lydia; Hofman, Véronique; Long-Mira, Elodie; Butori, Catherine; Selva, Eric; Merino-Trigo, Ana; Vénissac, Nicolas; Mouroux, Jérôme; Vrignaud, Patricia; Hofman, Paul

2015-02-01

With the ongoing need to improve therapy for non-small cell lung cancer (NSCLC) there has been increasing interest in developing reliable preclinical models to test novel therapeutics. Patient-derived tumor xenografts (PDX) are considered to be interesting candidates. However, the establishment of such model systems requires highly specialized research facilities and introduces logistic challenges. We aimed to establish an extensive well-characterized panel of NSCLC xenograft models in the context of a long-distance research network after careful control of the preanalytical steps. One hundred fresh surgically resected NSCLC specimens were shipped in survival medium at room temperature from a hospital-integrated biobank to animal facilities. Within 24 h post-surgery, tumor fragments were subcutaneously xenografted into immunodeficient mice. PDX characterization was performed by histopathological, immunohistochemical, aCGH and next-generation sequencing approaches. For this model system, the tumor take rate was 35%, with higher rates for squamous carcinoma (60%) than for adenocarcinoma (13%). Patients for whom PDX tumors were obtained had a significantly shorter disease-free survival (DFS) compared to patients for whom no PDX tumors (P = 0.039) were obtained. We established a large panel of PDX NSCLC models with a high frequency of mutations (29%) in EGFR, KRAS, NRAS, MEK1, BRAF, PTEN, and PI3KCA genes and with gene amplification (20%) of c-MET and FGFR1. This new patient-derived NSCLC xenograft collection, established regardless of the considerable time required and the distance between the clinic and the animal facilities, recapitulated the histopathology and molecular diversity of NSCLC and provides stable and reliable preclinical models for human lung cancer research. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Pre-analytical and analytical aspects affecting clinical reliability of plasma glucose results.

PubMed

Pasqualetti, Sara; Braga, Federica; Panteghini, Mauro

2017-07-01

The measurement of plasma glucose (PG) plays a central role in recognizing disturbances in carbohydrate metabolism, with established decision limits that are globally accepted. This requires that PG results are reliable and unequivocally valid no matter where they are obtained. To control the pre-analytical variability of PG and prevent in vitro glycolysis, the use of citrate as rapidly effective glycolysis inhibitor has been proposed. However, the commercial availability of several tubes with studies showing different performance has created confusion among users. Moreover, and more importantly, studies have shown that tubes promptly inhibiting glycolysis give PG results that are significantly higher than tubes containing sodium fluoride only, used in the majority of studies generating the current PG cut-points, with a different clinical classification of subjects. From the analytical point of view, to be equivalent among different measuring systems, PG results should be traceable to a recognized higher-order reference via the implementation of an unbroken metrological hierarchy. In doing this, it is important that manufacturers of measuring systems consider the uncertainty accumulated through the different steps of the selected traceability chain. In particular, PG results should fulfil analytical performance specifications defined to fit the intended clinical application. Since PG has tight homeostatic control, its biological variability may be used to define these limits. Alternatively, given the central diagnostic role of the analyte, an outcome model showing the impact of analytical performance of test on clinical classifications of subjects can be used. Using these specifications, performance assessment studies employing commutable control materials with values assigned by reference procedure have shown that the quality of PG measurements is often far from desirable and that problems are exacerbated using point-of-care devices. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Precise turnaround time measurement of laboratory processes using radiofrequency identification technology.

PubMed

Mayer, Horst; Brümmer, Jens; Brinkmann, Thomas

2011-01-01

To implement Lean Six Sigma in our central laboratory we conducted a project to measure single pre-analytical steps influencing turnaround time (TAT) of emergency department (ED) serum samples. The traditional approach of extracting data from the Laboratory Information System (LIS) for a retrospective calculation of a mean TAT is not suitable. Therefore, we used radiofrequency identification (RFID) chips for real time tracking of individual samples at any pre-analytical step. 1,200 serum tubes were labelled with RFID chips and were provided to the emergency department. 3 RFID receivers were installed in the laboratory: at the outlet of the pneumatic tube system, at the centrifuge, and in the analyser area. In addition, time stamps of sample entry at the automated sample distributor and communication of results from the analyser were collected from LIS. 1,023 labelled serum tubes arrived at our laboratory. 899 RFID tags were used for TAT calculation. The following transfer times were determined (median 95th percentile in min:sec): pneumatic tube system --> centrifuge (01:25/04:48), centrifuge --> sample distributor (14:06/5:33), sample distributor --> analysis system zone (02:39/15:07), analysis system zone --> result communication (12:42/22:21). Total TAT was calculated at 33:19/57:40 min:sec. Manual processes around centrifugation were identified as a major part of TAT with 44%/60% (median/95th percentile). RFID is a robust, easy to use, and error-free technology and not susceptible to interferences in the laboratory environment. With this study design we were able to measure significant variations in a single manual sample transfer process. We showed that TAT is mainly influenced by manual steps around the centrifugation process and we concluded that centrifugation should be integrated in solutions for total laboratory automation.

Implementation of a new 'community' laboratory CD4 service in a rural health district in South Africa extends laboratory services and substantially improves local reporting turnaround time.

PubMed

Coetzee, L M; Cassim, N; Glencross, D K

2015-12-16

The CD4 integrated service delivery model (ITSDM) provides for reasonable access to pathology services across South Africa (SA) by offering three new service tiers that extend services into remote, under-serviced areas. ITSDM identified Pixley ka Seme as such an under-serviced district. To address the poor service delivery in this area, a new ITSDM community (tier 3) laboratory was established in De Aar, SA. Laboratory performance and turnaround time (TAT) were monitored post implementation to assess the impact on local service delivery. Using the National Health Laboratory Service Corporate Data Warehouse, CD4 data were extracted for the period April 2012-July 2013 (n=11,964). Total mean TAT (in hours) was calculated and pre-analytical and analytical components assessed. Ongoing testing volumes, as well as external quality assessment performance across ten trials, were used to indicate post-implementation success. Data were analysed using Stata 12. Prior to the implementation of CD4 testing at De Aar, the total mean TAT was 20.5 hours. This fell to 8.2 hours post implementation, predominantly as a result of a lower pre-analytical mean TAT reducing from a mean of 18.9 to 1.8 hours. The analytical testing TAT remained unchanged after implementation and monthly test volumes increased by up to 20%. External quality assessment indicated adequate performance. Although subjective, questionnaires sent to facilities reported improved service delivery. Establishing CD4 testing in a remote community laboratory substantially reduces overall TAT. Additional community CD4 laboratories should be established in under-serviced areas, especially where laboratory infrastructure is already in place.

Laboratory diagnosis of gestational diabetes: An in silico investigation into the effects of pre-analytical processing on the diagnostic sensitivity and specificity of the oral glucose tolerance test.

PubMed

Mansell, Erin; Lunt, Helen; Docherty, Paul

2017-06-01

Delayed separation of red cells from plasma causes pre analytical glucose loss, which in turn results in an under-diagnosis of GDM (gestational diabetes) based on the OGTT (oral glucose tolerance test). In silico investigations may help laboratory decision making, when exploring pragmatic improvements to sample processing. Late pregnancy 0, 1 and 2h 75g OGTT values were obtained from two distinct populations of pregnant women: 1. Values derived from the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) Study and 2. New Zealand women identified as at higher risk of GDM by their caregivers, undergoing OGTT during routine antenatal care. In both populations studied, in silico modelling focussed on the effects of pre-analytical delays in plasma separation, when using fluoride collection tubes. Using a model that 'batched' samples from the three OGTT collection times, diagnostic sensitivity was estimated as follows: 66.1% for HAPO research population and 48.4% for the 1305 women receiving routine antenatal care. If samples were not batched, but processed shortly after each blood sample was collected, then sensitivity increased to 81%. Exploration of a range of clinical and laboratory scenarios using in silico modelling, showed that delaying the processing of pregnancy OGTT samples, using batched sample collection into fluoride tubes, causes unacceptable loss of GDM diagnostic sensitivity across two distinct population groups. This modelling approach will hopefully provide information that helps with final decision making around improved laboratory processing techniques. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Immunohistochemistry practices of cytopathology laboratories: a survey of participants in the College of American Pathologists Nongynecologic Cytopathology Education Program.

PubMed

Fischer, Andrew H; Schwartz, Mary R; Moriarty, Ann T; Wilbur, David C; Souers, Rhona; Fatheree, Lisa; Booth, Christine N; Clayton, Amy C; Kurtyz, Daniel F I; Padmanabhan, Vijayalakshmi; Crothers, Barbara A

2014-09-01

Immunohistochemistry (IHC) is important for cytology but poses special challenges because preanalytic conditions may differ from the conditions of IHC-positive controls. To broadly survey cytology laboratories to quantify preanalytic platforms for cytology IHC and identify problems with particular platforms or antigens. To discover how validation guidelines for HER2 testing have affected cytology. A voluntary survey of cytology IHC practices was sent to 1899 cytology laboratories participating in the College of American Pathologists Nongynecologic Cytopathology Education Program in the fall of 2009. A total of 818 laboratories (43%) responded to the survey by April 2010. Three hundred fourty-five of 791 respondents (44%) performed IHC on cytology specimens. Seventeen different fixation and processing platforms prior to antibody reaction were reported. A total of 59.2% of laboratories reported differences between the platforms for cytology specimens and positive controls, but most (155 of 184; 84%) did not alter antibody dilutions or antigen retrieval for cytology IHC. When asked to name 2 antibodies for which staining conditions differed between cytology and surgical samples, there were 18 responses listing 14 antibodies. A total of 30.6% of laboratories performing IHC offered HER2 testing before publication of the 2007 College of American Pathologists/American Society of Clinical Oncologists guidelines, compared with 33.6% afterward, with increased performance of testing by reference laboratories. Three laboratories validated a nonformalin HER2 platform. The platforms for cytology IHC and positive controls differ for most laboratories, yet conditions are uncommonly adjusted for cytology specimens. Except for the unsuitability of air-dried smears for HER2 testing, the survey did not reveal evidence of systematic problems with any antibody or platform.

Techniques used for the screening of hemoglobin levels in blood donors: current insights and future directions.

PubMed

Chaudhary, Rajendra; Dubey, Anju; Sonker, Atul

2017-01-01

Blood donor hemoglobin (Hb) estimation is an important donation test that is performed prior to blood donation. It serves the dual purpose of protecting the donors' health against anemia and ensuring good quality of blood components, which has an implication on recipients' health. Diverse cutoff criteria have been defined world over depending on population characteristics; however, no testing methodology and sample requirement have been specified for Hb screening. Besides the technique, there are several physiological and methodological factors that affect accuracy and reliability of Hb estimation. These include the anatomical source of blood sample, posture of the donor, timing of sample and several other biological factors. Qualitative copper sulfate gravimetric method has been the archaic time-tested method that is still used in resource-constrained settings. Portable hemoglobinometers are modern quantitative devices that have been further modified to reagent-free cuvettes. Furthermore, noninvasive spectrophotometry was introduced, mitigating pain to blood donor and eliminating risk of infection. Notwithstanding a tremendous evolution in terms of ease of operation, accuracy, mobility, rapidity and cost, a component of inherent variability persists, which may partly be attributed to pre-analytical variables. Hence, blood centers should pay due attention to validation of test methodology, competency of operating staff and regular proficiency testing of the outputs. In this article, we have reviewed various regulatory guidelines, described the variables that affect the measurements and compared the validated technologies for Hb screening of blood donors along with enumeration of their merits and limitations.

Causes and impact of specimen rejection in a clinical chemistry laboratory.

PubMed

Cao, Liyun; Chen, Meng; Phipps, Ron A; Del Guidice, Robert E; Handy, Beverly C; Wagar, Elizabeth A; Meng, Qing H

2016-07-01

Pre-analytical errors necessitate specimen rejection and negatively affect patient safety. Our purpose was to investigate the factors leading to specimen rejection and its impact. Specimen rejections in a clinical chemistry laboratory during a 1-year period were reviewed retrospectively and analyzed for frequency, cause, circumstances, and impact. Of the 837,862 specimens received, 2178 (0.26%) were rejected. The most common reasons for specimen rejection were contamination (n=764, 35.1%), inappropriate collection container/tube (n=330, 15.2%), quantity not sufficient (QNS) (n=329, 15.1%), labeling errors (n=321, 14.7%), hemolyzed specimen (n=205, 9.4%), and clotted specimen (n=203, 9.3%). The analytes most often affected were glucose (n=192, 8.8%); calcium (n=152, 7.0%), magnesium (n=148, 6.8%), potassium (n=137, 6.3%), creatinine (n=100, 4.6%), and blood urea nitrogen (n=97, 4.4%). Outpatient service and blood draw by phlebotomists were associated with low rejection rates (536/493,501 or 0.11% and 368/586,503 or 0.06%, respectively). Recollection due to specimen rejection increased the turnaround time by an average of 108min. The total cost for the recollection was around $43,210 USD with an average cost around $21.9 USD. The factors associated with rejection are remediable by improved training and quality assurance measures. Policies and procedures specific to specimen collection, transportation, and preparation should be strictly followed. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of Altering Various Image Parameters on Human Epidermal Growth Factor Receptor 2 Image Analysis Data Quality

PubMed Central

Pantanowitz, Liron; Liu, Chi; Huang, Yue; Guo, Huazhang; Rohde, Gustavo K.

2017-01-01

Introduction: The quality of data obtained from image analysis can be directly affected by several preanalytical (e.g., staining, image acquisition), analytical (e.g., algorithm, region of interest [ROI]), and postanalytical (e.g., computer processing) variables. Whole-slide scanners generate digital images that may vary depending on the type of scanner and device settings. Our goal was to evaluate the impact of altering brightness, contrast, compression, and blurring on image analysis data quality. Methods: Slides from 55 patients with invasive breast carcinoma were digitized to include a spectrum of human epidermal growth factor receptor 2 (HER2) scores analyzed with Visiopharm (30 cases with score 0, 10 with 1+, 5 with 2+, and 10 with 3+). For all images, an ROI was selected and four parameters (brightness, contrast, JPEG2000 compression, out-of-focus blurring) then serially adjusted. HER2 scores were obtained for each altered image. Results: HER2 scores decreased with increased illumination, higher compression ratios, and increased blurring. HER2 scores increased with greater contrast. Cases with HER2 score 0 were least affected by image adjustments. Conclusion: This experiment shows that variations in image brightness, contrast, compression, and blurring can have major influences on image analysis results. Such changes can result in under- or over-scoring with image algorithms. Standardization of image analysis is recommended to minimize the undesirable impact such variations may have on data output. PMID:28966838

Preanalytical influence of pneumatic tube delivery system on results of routine biochemistry and haematology analysis.

PubMed

Petit, Morgane; Mine, Louis; Pascreau, Tiffany; Brouzes, Chantal; Majoux, Sandrine; Borgel, Delphine; Beaudeux, Jean-Louis; Lasne, Dominique; Hennequin, Carole

2017-12-01

Pneumatic tube delivery system (PTS) enables to reduce considerably turnaround times. The aim of the study was to assess the influence of the PTS on the quality of routine biochemical and hematological tests in our laboratory. Blood samples from 6 hospitalized patients and 8 healthy volunteers were analyzed. Blood samples were delivered to the laboratory by a PTS and by a human courier. We performed the following analysis: ionized calcium, sodium, potassium, lactate deshydrogenase (LDH), aspartate aminotransferase (ASAT), arterial blood gas, complete blood count and coagulation test as prothrombin time, activated partial thromboplastin time, factors V and VIII. Results were compared between the both method of transport according to the recommendation of the Société française de biologie clinique and the French committee for accreditation (SH-GTA01, norme NF ISO 5275-6). The hemolysis index of plasma was similar between the groups and no morphological differences were found on blood cells. For three samples, when delivered by PTS, LDH levels (two samples) and neutrophil polynuclear count (one sample) were above the recommended guidelines compared to those delivered by courier. Conversely, LDH levels and FVIII were below in two samples delivered by PTS. LDH levels, PNN count or factor VIII can be affected by PTS without the clinical interpretation being modified. We concluded that the PTS can be used to transport blood samples for routine biochemical and hematological analysis in our hospital.

Stability of pro-gastrin-releasing peptide in serum versus plasma.

PubMed

Yoshimura, Toru; Fujita, Kenju; Kawakami, Satoshi; Takeda, Katsumichi; Chan, Sabrina; Beligere, Gangamani; Dowell, Barry

2008-01-01

Although serum assays for pro-gastrin-releasing peptide (ProGRP) assays have been commercially available in Japan for several years, the stability of ProGRP in serum and plasma has not been well documented. We investigated the stability of ProGRP in serum and plasma with fresh and stored (frozen) specimens, as well as the cause of the observed instability in serum. ProGRP concentrations in fresh serum were decreased by 6-28% after room temperature storage for 2 h and by 8-32% after 2-8 degrees C storage for 24 h. The average change in ProGRP concentrations in fresh plasma was within +/-10% of baseline for more than 4 h at room temperature and for more than 24 h at 2-8 degrees C. The incubation of a serine protease, thrombin (activated blood coagulation factor II), in a buffer solution containing ProGRP caused decreases in ProGRP concentrations. Following the addition of phenylmethylsulfonyl fluoride, a serine protease inhibitor, to serum, the serum stability for ProGRP was similar to that in plasma. ProGRP is significantly more stable in plasma than in serum. We speculate that thrombin in serum is one of the factors that inactivate ProGRP in serum by proteolysis of the ProGRP antigen. The use of plasma samples for ProGRP may improve the clinical reliability of this marker by minimizing preanalytical changes in ProGRP concentrations. (c) 2008 S. Karger AG, Basel.

Improving the quality of biomarker discovery research: the right samples and enough of them.

PubMed

Pepe, Margaret S; Li, Christopher I; Feng, Ziding

2015-06-01

Biomarker discovery research has yielded few biomarkers that validate for clinical use. A contributing factor may be poor study designs. The goal in discovery research is to identify a subset of potentially useful markers from a large set of candidates assayed on case and control samples. We recommend the PRoBE design for selecting samples. We propose sample size calculations that require specifying: (i) a definition for biomarker performance; (ii) the proportion of useful markers the study should identify (Discovery Power); and (iii) the tolerable number of useless markers amongst those identified (False Leads Expected, FLE). We apply the methodology to a study of 9,000 candidate biomarkers for risk of colon cancer recurrence where a useful biomarker has positive predictive value ≥ 30%. We find that 40 patients with recurrence and 160 without recurrence suffice to filter out 98% of useless markers (2% FLE) while identifying 95% of useful biomarkers (95% Discovery Power). Alternative methods for sample size calculation required more assumptions. Biomarker discovery research should utilize quality biospecimen repositories and include sample sizes that enable markers meeting prespecified performance characteristics for well-defined clinical applications to be identified. The scientific rigor of discovery research should be improved. ©2015 American Association for Cancer Research.

Urinary concentrations of environmental phenols in pregnant women in a pilot study of the National Children's Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mortensen, Mary E., E-mail: MMortensen@cdc.gov; Calafat, Antonia M.; Ye, Xiaoyun

Environmental phenols are a group of chemicals with widespread uses in consumer and personal care products, food and beverage processing, and in pesticides. We assessed exposure to benzophenone-3, bisphenol A (BPA), triclosan, methyl- and propyl parabens, and 2,4- and 2,5-dichlorophenol or their precursors in 506 pregnant women enrolled in the National Children's Study (NCS) Vanguard Study. We measured the urinary concentrations of the target phenols by using online solid-phase extraction–isotope dilution high performance liquid chromatography–tandem mass spectrometry. NCS women results were compared to those of 524 similar-aged women in the National Health and Nutrition Examination Survey (NHANES) 2009–2010, and tomore » 174 pregnant women in NHANES 2005–2010. In the NCS women, we found significant racial/ethnic differences (p<0.05) in regression adjusted mean concentrations of benzophenone-3, triclosan, 2,4- and 2,5-dichlorophenol, but not of BPA. Urinary 2,4- and 2,5-dichlorophenol concentrations were highly correlated (r=0.66, p<0.0001). Except for BPA and triclosan, adjusted mean concentrations were significantly different across the 7 study sites. Education was marginally significant for benzophenone-3, triclosan, propyl paraben, and 2,5-dichlorophenol. Urinary concentrations of target phenols in NCS pregnant women and U.S. women and pregnant women were similar. In NCS pregnant women, race/ethnicity and geographic location determined urinary concentrations of most phenols (except BPA), suggesting differential exposures. NCS Main Study protocols should collect urine biospecimens and information about exposures to environmental phenols. - Highlights: • Limited biomonitoring data are available in pregnant women. • Seven urinary phenols were measured in 506 third trimester women enrolled in the NCS. • Urine benzophenone-3, triclosan, 2,4- and 2,5-dichlorophenol differed by race/ethnicity. • Urinary concentrations of 2,4- and 2,5-dichlorophenol were highly correlated. • Exposure information can expand the utility of biospecimens in the NCS Main Study.« less

Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development--the LIFE Study.

PubMed

Buck Louis, Germaine M; Schisterman, Enrique F; Sweeney, Anne M; Wilcosky, Timothy C; Gore-Langton, Robert E; Lynch, Courtney D; Boyd Barr, Dana; Schrader, Steven M; Kim, Sungduk; Chen, Zhen; Sundaram, Rajeshwari

2011-09-01

The relationship between the environment and human fecundity and fertility remains virtually unstudied from a couple-based perspective in which longitudinal exposure data and biospecimens are captured across sensitive windows. In response, we completed the LIFE Study with methodology that intended to empirically evaluate a priori purported methodological challenges: implementation of population-based sampling frameworks suitable for recruiting couples planning pregnancy; obtaining environmental data across sensitive windows of reproduction and development; home-based biospecimen collection; and development of a data management system for hierarchical exposome data. We used two sampling frameworks (i.e., fish/wildlife licence registry and a direct marketing database) for 16 targeted counties with presumed environmental exposures to persistent organochlorine chemicals to recruit 501 couples planning pregnancies for prospective longitudinal follow-up while trying to conceive and throughout pregnancy. Enrolment rates varied from <1% of the targeted population (n = 424,423) to 42% of eligible couples who were successfully screened; 84% of the targeted population could not be reached, while 36% refused screening. Among enrolled couples, ∼ 85% completed daily journals while trying; 82% of pregnant women completed daily early pregnancy journals, and 80% completed monthly pregnancy journals. All couples provided baseline blood/urine samples; 94% of men provided one or more semen samples and 98% of women provided one or more saliva samples. Women successfully used urinary fertility monitors for identifying ovulation and home pregnancy test kits. Couples can be recruited for preconception cohorts and will comply with intensive data collection across sensitive windows. However, appropriately sized sampling frameworks are critical, given the small percentage of couples contacted found eligible and reportedly planning pregnancy at any point in time. © Published 2011. This article is a US Government work and is in the public domain in the USA.

A Multidisciplinary Biospecimen Bank of Renal Cell Carcinomas Compatible with Discovery Platforms at Mayo Clinic, Scottsdale, Arizona

PubMed Central

Ho, Thai H.; Nateras, Rafael Nunez; Yan, Huihuang; Park, Jin G.; Jensen, Sally; Borges, Chad; Lee, Jeong Heon; Champion, Mia D.; Tibes, Raoul; Bryce, Alan H.; Carballido, Estrella M.; Todd, Mark A.; Joseph, Richard W.; Wong, William W.; Parker, Alexander S.; Stanton, Melissa L.; Castle, Erik P.

2015-01-01

To address the need to study frozen clinical specimens using next-generation RNA, DNA, chromatin immunoprecipitation (ChIP) sequencing and protein analyses, we developed a biobank work flow to prospectively collect biospecimens from patients with renal cell carcinoma (RCC). We describe our standard operating procedures and work flow to annotate pathologic results and clinical outcomes. We report quality control outcomes and nucleic acid yields of our RCC submissions (N=16) to The Cancer Genome Atlas (TCGA) project, as well as newer discovery platforms, by describing mass spectrometry analysis of albumin oxidation in plasma and 6 ChIP sequencing libraries generated from nephrectomy specimens after histone H3 lysine 36 trimethylation (H3K36me3) immunoprecipitation. From June 1, 2010, through January 1, 2013, we enrolled 328 patients with RCC. Our mean (SD) TCGA RNA integrity numbers (RINs) were 8.1 (0.8) for papillary RCC, with a 12.5% overall rate of sample disqualification for RIN <7. Banked plasma had significantly less albumin oxidation (by mass spectrometry analysis) than plasma kept at 25°C (P<.001). For ChIP sequencing, the FastQC score for average read quality was at least 30 for 91% to 95% of paired-end reads. In parallel, we analyzed frozen tissue by RNA sequencing; after genome alignment, only 0.2% to 0.4% of total reads failed the default quality check steps of Bowtie2, which was comparable to the disqualification ratio (0.1%) of the 786-O RCC cell line that was prepared under optimal RNA isolation conditions. The overall correlation coefficients for gene expression between Mayo Clinic vs TCGA tissues ranged from 0.75 to 0.82. These data support the generation of high-quality nucleic acids for genomic analyses from banked RCC. Importantly, the protocol does not interfere with routine clinical care. Collections over defined time points during disease treatment further enhance collaborative efforts to integrate genomic information with outcomes. PMID:26181416

Overcoming challenges in designing and implementing a phase II randomized controlled trial using a presurgical model to test a dietary intervention in prostate cancer

PubMed Central

George, Stephen L; Switzer, Boyd R; Snyder, Denise C; Madden, John F; Polascik, Thomas J; Ruffin, Mack T; Vollmer, Robin T

2008-01-01

Background The time between the diagnosis of cancer and a planned definitive surgical procedure offers a strong and direct approach for assessing the impact of interventions (including lifestyle interventions) on the biology of the target tissue and the tumor. Despite the many strengths of presurgical models, there are practical issues and challenges that arise when using this approach. Purpose/Methods We recently completed an NIH-funded phase II trial that utilized a presurgical model in testing the comparative effects of flaxseed supplementation and/or dietary fat restriction on the biology and biomarkers associated with prostatic carcinoma. Herein, we report the rationale for our original design, discuss modifications in strategy, and relay experiences in implementing this trial related to the following topics: (1) subject accrual; (2) subject retention; (3) intervention delivery; and (4) retrieval and completion rates regarding the collection of paraffin-embedded and fresh frozen prostate tissue, blood, urine, ejaculate, anthropometric measures and survey data. Results This trial achieved its accrual target, i.e., a racially-representative (70% white, 30% minority) sample of 161 participants, low rates of attrition (7%); and collection rates that exceeded 90% for almost all biospecimens and survey data. While the experience gained from pilot studies was invaluable in designing this trial, the complexity introduced by the collection of several biospecimens, inclusion of a team of pathologists (to provide validated readings), and shifts in practice patterns related to prostatectomy, made it necessary to revise our protocol; lessons from our experiences are offered within this article. Conclusions While our experience specifically relates to the implementation of a presurgical model-based trial in prostate cancer aimed at testing flaxseed-supplemented and fat-restricted diets, many of the lessons learned have broad application to trials that utilize a presurgical model or dietary modification within various cancer populations. PMID:18559416

Benefits and Risks in Secondary Use of Digitized Clinical Data: Views of Community Members Living in a Predominantly Ethnic Minority Urban Neighborhood

PubMed Central

Lucero, Robert J.; Kearney, Joan; Cortes, Yamnia; Arcia, Adriana; Appelbaum, Paul; Fernández, Roberto Lewis; Luchsinger, Jose

2015-01-01

Background There is potential to increase the speed of scientific discovery and implement personalized health care by using digitized clinical data collected on the patient care experience. The use of these data in research raises concerns about the privacy and confidentiality of personal health information. This study explored community members’ views on the secondary use of digitized clinical data to (1) recruit participants for clinical studies; (2) recruit family members of persons with an index condition for primary studies; and (3) conduct studies of information related to stored biospecimens. Methods A qualitative descriptive design was used to examine the bioethical issues outlined from the perspective of urban-dwelling community members. Focus groups were used for data collection, and emergent content analysis was employed to organize and interpret the data. Results Thirty community members attended one of four focus groups ranging in size from 4 to 11 participants. Five critical themes emerged from the focus-group material: (1) perceived motivators for research participation; (2) objective or “real-life” barriers to research participation; (3) a psychological component of uncertainty and mistrust; (4) preferred mechanisms for recruitment and participation; and (5) cultural characteristics that can impact understanding and willingness to engage in research. Conclusions The overriding concern of community members regarding research participation and/or secondary clinical and nonclinical use of digitized information was that their involvement would be safe and the outcome would be meaningful to them and to others. According to participants, biospecimens acquired during routine clinical visits or for research are no longer possessions of the participant. Although the loss of privacy was a concern for participants, they preferred that researchers access their personal health information using a digitized clinical file rather than through a paper-based medical record. PMID:26101782

National ethics guidance in Sub-Saharan Africa on the collection and use of human biological specimens: a systematic review.

PubMed

Barchi, Francis; Little, Madison T

2016-10-22

Ethical and regulatory guidance on the collection and use of human biospecimens (HBS) for research forms an essential component of national health systems in Sub-Saharan Africa (SSA), where rapid advances in genetic- and genomic-based technologies are fueling clinical trials involving HBS and the establishment of large-scale biobanks. An extensive multi-level search for publicly available ethics regulatory guidance was conducted for each SSA country. A second review documented active trials listed in the WHO International Clinical Trials Registry Platform as of January 2015 in which HBS collection was specified in the protocol. Findings were combined to determine the extent to which countries that are study sites for HBS-related research are supported by regulatory guidance language on the collection, use, ownership and storage of biospecimens. Of the 49 SSA countries, 29 had some form of national ethics guidance, yet only 17 provided language relating to HBS-related research, with specific guidance on consent (14), ownership (6), reuse (10), storage (9), and export/import/transfer (13). Ten countries accounted for 84 % of the active clinical trials involving the collection of HBS in SSA. All except one of these countries were found to have some national guidance in the form of regulations, codes of ethics, and/or standard operating procedures; however, only seven of the ten offered any language specific to HBS. Despite the fact that the bulk of registered clinical trials in SSA involving HBS, as well as existing and proposed sites for biorepositories under the H3Africa Initiative, are currently situated in countries with the most complete ethics and regulatory guidance, variability in the regulations themselves may create challenges for planned and future pan-African collaborations and may require legislative action at the national level to revise. Countries in SSA that still lack regulatory guidance on HBS will require extensive health system strengthening in ethics governance before they can be full participants in the modern research enterprise.

Baseline Profile of Participants in the Japan Environment and Children's Study (JECS).

PubMed

Michikawa, Takehiro; Nitta, Hiroshi; Nakayama, Shoji F; Yamazaki, Shin; Isobe, Tomohiko; Tamura, Kenji; Suda, Eiko; Ono, Masaji; Yonemoto, Junzo; Iwai-Shimada, Miyuki; Kobayashi, Yayoi; Suzuki, Go; Kawamoto, Toshihiro

2018-02-05

The Japan Environment and Children's Study (JECS), known as Ecochil-Chosa in Japan, is a nationwide birth cohort study investigating the environmental factors that might affect children's health and development. We report the baseline profiles of the participating mothers, fathers, and their children. Fifteen Regional Centres located throughout Japan were responsible for recruiting women in early pregnancy living in their respective recruitment areas. Self-administered questionnaires and medical records were used to obtain such information as demographic factors, lifestyle, socioeconomic status, environmental exposure, medical history, and delivery information. In the period up to delivery, we collected bio-specimens, including blood, urine, hair, and umbilical cord blood. Fathers were also recruited, when accessible, and asked to fill in a questionnaire and to provide blood samples. The total number of pregnancies resulting in delivery was 100,778, of which 51,402 (51.0%) involved program participation by male partners. Discounting pregnancies by the same woman, the study included 95,248 unique mothers and 49,189 unique fathers. The 100,778 pregnancies involved a total of 101,779 fetuses and resulted in 100,148 live births. The coverage of children in 2013 (the number of live births registered in JECS divided by the number of all live births within the study areas) was approximately 45%. Nevertheless, the data on the characteristics of the mothers and children we studied showed marked similarity to those obtained from Japan's 2013 Vital Statistics Survey. Between 2011 and 2014, we established one of the largest birth cohorts in the world.

Baseline Profile of Participants in the Japan Environment and Children’s Study (JECS)

PubMed Central

Nitta, Hiroshi; Nakayama, Shoji F.; Yamazaki, Shin; Isobe, Tomohiko; Tamura, Kenji; Suda, Eiko; Ono, Masaji; Yonemoto, Junzo; Iwai-Shimada, Miyuki; Kobayashi, Yayoi; Suzuki, Go; Kawamoto, Toshihiro

2018-01-01

Background The Japan Environment and Children’s Study (JECS), known as Ecochil-Chosa in Japan, is a nationwide birth cohort study investigating the environmental factors that might affect children’s health and development. We report the baseline profiles of the participating mothers, fathers, and their children. Methods Fifteen Regional Centres located throughout Japan were responsible for recruiting women in early pregnancy living in their respective recruitment areas. Self-administered questionnaires and medical records were used to obtain such information as demographic factors, lifestyle, socioeconomic status, environmental exposure, medical history, and delivery information. In the period up to delivery, we collected bio-specimens, including blood, urine, hair, and umbilical cord blood. Fathers were also recruited, when accessible, and asked to fill in a questionnaire and to provide blood samples. Results The total number of pregnancies resulting in delivery was 100,778, of which 51,402 (51.0%) involved program participation by male partners. Discounting pregnancies by the same woman, the study included 95,248 unique mothers and 49,189 unique fathers. The 100,778 pregnancies involved a total of 101,779 fetuses and resulted in 100,148 live births. The coverage of children in 2013 (the number of live births registered in JECS divided by the number of all live births within the study areas) was approximately 45%. Nevertheless, the data on the characteristics of the mothers and children we studied showed marked similarity to those obtained from Japan’s 2013 Vital Statistics Survey. Conclusions Between 2011 and 2014, we established one of the largest birth cohorts in the world. PMID:29093304

Immuno-analysis of microparticles: probing at the limits of detection

PubMed Central

Latham, Sharissa L.; Tiberti, Natalia; Gokoolparsadh, Naveena; Holdaway, Karen; Olivier Couraud, Pierre; Grau, Georges E. R.; Combes, Valery

2015-01-01

Microparticle (MP) research is clouded by debate regarding the accuracy and validity of flow cytometry (FCM) as an analytical methodology, as it is influenced by many variables including the pre-analytical conditions, instruments physical capabilities and detection parameters. This study utilises a simplistic in vitro system for generating MP, and through comparative analysis with immuno-electron microscopy (Immuno-EM) assesses the strengths and limitations of probe selection and high-sensitivity FCM. Of the markers examined, MP were most specifically labelled with phosphatidylserine ligands, annexin V and lactadherin, although only ~60% MP are PS positive. Whilst these two ligands detect comparable absolute MP numbers, they interact with the same population in distinct manners; annexin V binding is enhanced on TNF induced MP. CD105 and CD54 expression were, as expected, consistent and enhanced following TNF activation respectively. Their labelling however accounted for as few as 30–40% of MP. The greatest discrepancies between FCM and I-EM were observed in the population solely labelled for the surface antigen. These findings demonstrate that despite significant improvements in resolution, high-sensitivity FCM remains limited in detecting small-size MP expressing low antigen levels. This study highlights factors to consider when selecting endothelial MP probes, as well as interpreting and representing data. PMID:26553743

Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study.

PubMed

Kruse, Niels; Persson, Staffan; Alcolea, Daniel; Bahl, Justyna M C; Baldeiras, Ines; Capello, Elisabetta; Chiasserini, Davide; Bocchio Chiavetto, Luisella; Emersic, Andreja; Engelborghs, Sebastiaan; Eren, Erden; Fladby, Tormod; Frisoni, Giovanni; García-Ayllón, María-Salud; Genc, Sermin; Gkatzima, Olymbia; Heegaard, Niels H H; Janeiro, André M; Kováčech, Branislav; Kuiperij, H Bea; Leitão, Maria J; Lleó, Alberto; Martins, Madalena; Matos, Mafalda; Mollergard, Hanne M; Nobili, Flavio; Öhrfelt, Annika; Parnetti, Lucilla; de Oliveira, Catarina Resende; Rot, Uros; Sáez-Valero, Javier; Struyfs, Hanne; Tanassi, Julia T; Taylor, Peggy; Tsolaki, Magda; Vanmechelen, Eugeen; Verbeek, Marcel M; Zilka, Norbert; Blennow, Kaj; Zetterberg, Henrik; Mollenhauer, Brit

2015-09-01

Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program - Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given. Copyright © 2015 Elsevier Inc. All rights reserved.

An Evidence-Based Approach to the Assessment of Heart-Type Fatty Acid Binding Protein in Acute Coronary Syndrome

PubMed Central

Viswanathan, Karthik; Hall, Alistair S; Barth, Julian H

2012-01-01

Cardiac troponins have been the biomarkers of choice for the diagnosis of acute coronary syndrome (ACS) for over a decade. There has, however, been considerable interest over the last two decades for newer biomarkers that would bring added value to the measurement of troponin such as the provision of prognosis and assistance in the choice of therapeutic interventions. In this manuscript, we review the development of heart-type fatty acid binding protein (H-FABP) in patients with ACS using the evidence-based laboratory medicine format. Phase I studies have established that H-FABP reference intervals and pre-analytical factors influencing H-FABP. Phase II studies have confirmed a) that H-FABP is elevated in patients with established myocardial infarction; b) that its serum concentration is related to the extent of infarction using survival as a surrogate; and c) that its use in chest pain patients can identify ACS patients and also provide prognostic information on survival. Furthermore, it is an independent prognostic marker for patients with suspected ACS who are troponin negative. Phase III studies involving randomised control trials for diagnosis and prognosis have not yet been performed and Phase IV studies await uptake of H-FABP in a routine service. PMID:22363093

A Survey of the Current Situation of Clinical Biobanks in China.

PubMed

Li, Haiyan; Ni, Mingyu; Wang, Peng; Wang, Xiaomin

2017-06-01

The development of biomedical research urgently needs the support of a large number of high-quality clinical biospecimens. Therefore, human biobanks at different levels have been established successively in China and other countries at a significantly increasing pace in recent years. To better understand the general current state of clinical biobanks in China, we surveyed 42 clinical biobanks based in hospitals and collected information involving their management systems, sharing mechanisms, quality control systems, and informational management systems using closed questionnaire methods. Based on our current information, there has not been such a large-scale survey in China. An understanding of the status and challenges current clinical biobanks face will provide valuable insights for the construction and sustainable development of higher quality clinical biobanks.

Satisfying regulatory and accreditation requirements for quality control.

PubMed

Ehrmeyer, Sharon S

2013-03-01

The Clinical Laboratory Improvement Amendments of 1988 (CLIA) requires all US clinical laboratories that test "materials derived from the human body for the purpose of providing information for the diagnosis, prevention, or treatment of any disease..." to be regulated. The CLIA mandates are site neutral; based on test complexity; and focus on the three phases of the testing process (preanalytical, analytical, and postanalytical). Many testing sites choose to meet the CLIA requirements by following the testing standards of a professional accreditation organization deemed by the Centers for Medicare and Medicaid Services. The three principal organizations are The Joint Commission, the College of American Pathologists, and COLA. Copyright © 2013 Elsevier Inc. All rights reserved.

"Bed Side" Human Milk Analysis in the Neonatal Intensive Care Unit: A Systematic Review.

PubMed

Fusch, Gerhard; Kwan, Celia; Kotrri, Gynter; Fusch, Christoph

2017-03-01

Human milk analyzers can measure macronutrient content in native breast milk to tailor adequate supplementation with fortifiers. This article reviews all studies using milk analyzers, including (i) evaluation of devices, (ii) the impact of different conditions on the macronutrient analysis of human milk, and (iii) clinical trials to improve growth. Results lack consistency, potentially due to systematic errors in the validation of the device, or pre-analytical sample preparation errors like homogenization. It is crucial to introduce good laboratory and clinical practice when using these devices; otherwise a non-validated clinical usage can severely affect growth outcomes of infants. Copyright © 2016 Elsevier Inc. All rights reserved.

The Da Vinci European BioBank: A Metabolomics-Driven Infrastructure

PubMed Central

Carotenuto, Dario; Luchinat, Claudio; Marcon, Giordana; Rosato, Antonio; Turano, Paola

2015-01-01

We present here the organization of the recently-constituted da Vinci European BioBank (daVEB, https://www.davincieuropeanbiobank.org/it). The biobank was created as an infrastructure to support the activities of the Fiorgen Foundation (http://www.fiorgen.net/), a nonprofit organization that promotes research in the field of pharmacogenomics and personalized medicine. The way operating procedures concerning samples and data have been developed at daVEB largely stems from the strong metabolomics connotation of Fiorgen and from the involvement of the scientific collaborators of the foundation in international/European projects aimed to tackle the standardization of pre-analytical procedures and the promotion of data standards in metabolomics. PMID:25913579

Recommendations for accreditation of laboratories in molecular biology of hematologic malignancies.

PubMed

Flandrin-Gresta, Pascale; Cornillet, Pascale; Hayette, Sandrine; Gachard, Nathalie; Tondeur, Sylvie; Mauté, Carole; Cayuela, Jean-Michel

2015-01-01

Over recent years, the development of molecular biology techniques has improved the hematological diseases diagnostic and follow-up. Consequently, these techniques are largely used in the biological screening of these diseases; therefore the Hemato-oncology molecular diagnostics laboratories must be actively involved in the accreditation process according the ISO 15189 standard. The French group of molecular biologists (GBMHM) provides requirements for the implementation of quality assurance for the medical molecular laboratories. This guideline states the recommendations for the pre-analytical, analytical (methods validation procedures, quality controls, reagents), and post-analytical conditions. In addition, herein we state a strategy for the internal quality control management. These recommendations will be regularly updated.

Guide to detecting epidermal growth factor receptor (EGFR) mutations in ctDNA of patients with advanced non-small-cell lung cancer

PubMed Central

Normanno, Nicola; Denis, Marc G.; Thress, Kenneth S.; Ratcliffe, Marianne; Reck, Martin

2017-01-01

Cancer treatment is evolving towards therapies targeted at specific molecular abnormalities that drive tumor growth. Consequently, to determine which patients are eligible, accurate assessment of molecular aberrations within tumors is required. Obtaining sufficient tumor tissue for molecular testing can present challenges; therefore, circulating free tumor-derived DNA (ctDNA) found in blood plasma has been proposed as an alternative source of tumor DNA. The diagnostic utility of ctDNA for the detection of epidermal growth factor receptor (EGFR) mutations harbored in tumors of patients with advanced non-small-cell lung cancer (NSCLC) is supported by the results of several large studies/meta-analyses. However, recent real-world studies suggest that the performance of ctDNA testing varies between geographic regions/laboratories, demonstrating the need for standardized guidance. In this review, we outline recommendations for obtaining an accurate result using ctDNA, relating to pre-analytical plasma processing, ctDNA extraction, and appropriate EGFR mutation detection methods, based on clinical trial results. We conclude that there are several advantages associated with ctDNA, including the potential for repeated sampling particularly following progression after first-line tyrosine kinase inhibitor (TKI) therapy, as TKIs targeting resistance mutations (eg T790M) are now approved for use in the USA/EU/Japan (at time of writing). However, evidence suggests that ctDNA does not allow detection of EGFR mutations in all patients with known mutation-positive NSCLC. Therefore, although tumor tissue should be the first sample choice for EGFR testing at diagnosis, ctDNA is a promising alternative diagnostic approach. PMID:27980215

CSF beta-amyloid 1–42 – what are we measuring in Alzheimer's disease?

PubMed Central

Hu, William T; Watts, Kelly D; Shaw, Leslie M; Howell, Jennifer C; Trojanowski, John Q; Basra, Sundeep; Glass, Jonathan D; Lah, James J; Levey, Allan I

2015-01-01

Objective To characterize biological and technical factors which influence cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker levels, including the presence of apolipoprotein E (APOE) ε4 allele, AD diagnosis, Aβ-binding proteins, sample processing, and preanalytical handling. Methods CSF was collected from 140 subjects with normal cognition, mild cognitive impairment, AD, and non-AD dementia. CSF levels of beta-amyloid 1–42 (Aβ42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) were analyzed following the standard and modified protocols. CSF levels of apoJ, apoE, albumin, and α-synuclein were measured in a subgroup (n = 69), and their effects on measured AD biomarker levels were also determined in vitro using human CSF samples. Results CSF Aβ42 levels measured using the AD Neuro-imaging Initiative (ADNI) protocol (which we call suspended Aβ42 or susAβ) were lower than total measurable CSF Aβ42 in all groups, and on average represents 57% of the latter. Logistic regression analysis showed this proportion (% susAβ) to be directly correlated with CSF Aβ42 and apoJ levels, but inversely correlated with CSF t-Tau levels. Finally, we showed in vitro that increasing apoE and apoJ levels directly increased % susAβ. Conclusion CSF susAβ levels are influenced by biological and technical factors, and may represent a marker of Aβ susceptible to lipoprotein-mediated clearance. Clinical trials should include total measurable Aβ42 and susAβ to better inform outcomes. PMID:25750918

Reproducibility of Interferon Gamma (IFN-γ) Release Assays. A Systematic Review

PubMed Central

Tagmouti, Saloua; Slater, Madeline; Benedetti, Andrea; Kik, Sandra V.; Banaei, Niaz; Cattamanchi, Adithya; Metcalfe, John; Dowdy, David; van Zyl Smit, Richard; Dendukuri, Nandini

2014-01-01

Rationale: Interferon gamma (IFN-γ) release assays for latent tuberculosis infection result in a larger-than-expected number of conversions and reversions in occupational screening programs, and reproducibility of test results is a concern. Objectives: Knowledge of the relative contribution and extent of the individual sources of variability (immunological, preanalytical, or analytical) could help optimize testing protocols. Methods: We performed a systematic review of studies published by October 2013 on all potential sources of variability of commercial IFN-γ release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB). The included studies assessed test variability under identical conditions and under different conditions (the latter both overall and stratified by individual sources of variability). Linear mixed effects models were used to estimate within-subject SD. Measurements and Main Results: We identified a total of 26 articles, including 7 studies analyzing variability under the same conditions, 10 studies analyzing variability with repeat testing over time under different conditions, and 19 studies reporting individual sources of variability. Most data were on QuantiFERON (only three studies on T-SPOT.TB). A considerable number of conversions and reversions were seen around the manufacturer-recommended cut-point. The estimated range of variability of IFN-γ response in QuantiFERON under identical conditions was ±0.47 IU/ml (coefficient of variation, 13%) and ±0.26 IU/ml (30%) for individuals with an initial IFN-γ response in the borderline range (0.25–0.80 IU/ml). The estimated range of variability in noncontrolled settings was substantially larger (±1.4 IU/ml; 60%). Blood volume inoculated into QuantiFERON tubes and preanalytic delay were identified as key sources of variability. Conclusions: This systematic review shows substantial variability with repeat IFN-γ release assays testing even under identical conditions, suggesting that reversions and conversions around the existing cut-point should be interpreted with caution. PMID:25188809

EC4 European Syllabus for Post-Graduate Training in Clinical Chemistry and Laboratory Medicine: version 3 - 2005.

PubMed

Zerah, Simone; McMurray, Janet; Bousquet, Bernard; Baum, Hannsjorg; Beastall, Graham H; Blaton, Vic; Cals, Marie-Josèphe; Duchassaing, Danielle; Gaudeau-Toussaint, Marie-Françoise; Harmoinen, Aimo; Hoffmann, Hans; Jansen, Rob T; Kenny, Desmond; Kohse, Klaus P; Köller, Ursula; Gobert, Jean-Gérard; Linget, Christine; Lund, Erik; Nubile, Giuseppe; Opp, Matthias; Pazzagli, Mario; Pinon, Georges; Queralto, José M; Reguengo, Henrique; Rizos, Demetrios; Szekeres, Thomas; Vidaud, Michel; Wallinder, Hans

2006-01-01

The EC4 Syllabus for Postgraduate Training is the basis for the European Register of Specialists in Clinical Chemistry and Laboratory Medicine. The syllabus: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. The syllabus is not primarily meant to be a training guide, but on the basis of the overview given (common minimal programme), national societies should formulate programmes that indicate where knowledge and experience is needed. The main points of this programme are: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. Knowledge in biochemistry, haematology, immunology, etc.; Pre-analytical conditions; Evaluation of results; Interpretations (post-analytical phase); Laboratory management; and Quality insurance management. The aim of this version of the syllabus is to be in accordance with the Directive of Professional Qualifications published on 30 September 2005. To prepare the common platforms planned in this directive, the disciplines are divided into four categories: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. Knowledge in biochemistry, haematology, immunology, etc.; Pre-analytical conditions; Evaluation of results; Interpretations (post-analytical phase); Laboratory management; and Quality insurance management. General chemistry, encompassing biochemistry, endocrinology, chemical (humoral), immunology, toxicology, and therapeutic drug monitoring; Haematology, covering cells, transfusion serology, coagulation, and cellular immunology; Microbiology, involving bacteriology, virology, parasitology, and mycology; Genetics and IVF.

A New Approach to Standardize Multicenter Studies: Mobile Lab Technology for the German Environmental Specimen Bank

PubMed Central

Lermen, Dominik; Schmitt, Daniel; Bartel-Steinbach, Martina; Schröter-Kermani, Christa; Kolossa-Gehring, Marike; von Briesen, Hagen; Zimmermann, Heiko

2014-01-01

Technical progress has simplified tasks in lab diagnosis and improved quality of test results. Errors occurring during the pre-analytical phase have more negative impact on the quality of test results than errors encountered during the total analytical process. Different infrastructures of sampling sites can highly influence the quality of samples and therewith of analytical results. Annually the German Environmental Specimen Bank (ESB) collects, characterizes, and stores blood, plasma, and urine samples of 120–150 volunteers each on four different sampling sites in Germany. Overarching goal is to investigate the exposure to environmental pollutants of non-occupational exposed young adults combining human biomonitoring with questionnaire data. We investigated the requirements of the study and the possibility to realize a highly standardized sampling procedure on a mobile platform in order to increase the required quality of the pre-analytical phase. The results lead to the development of a mobile epidemiologic laboratory (epiLab) in the project “Labor der Zukunft” (future’s lab technology). This laboratory includes a 14.7 m2 reception area to record medical history and exposure-relevant behavior, a 21.1 m2 examination room to record dental fillings and for blood withdrawal, a 15.5 m2 biological safety level 2 laboratory to process and analyze samples on site including a 2.8 m2 personnel lock and a 3.6 m2 cryofacility to immediately freeze samples. Frozen samples can be transferred to their final destination within the vehicle without breaking the cold chain. To our knowledge, we herewith describe for the first time the implementation of a biological safety laboratory (BSL) 2 lab and an epidemiologic unit on a single mobile platform. Since 2013 we have been collecting up to 15.000 individual human samples annually under highly standardized conditions using the mobile laboratory. Characterized and free of alterations they are kept ready for retrospective analyses in their final archive, the German ESB. PMID:25141120

Preanalytical variables and phosphoepitope expression in FFPE tissue: quantitative epitope assessment after variable cold ischemic time.

PubMed

Vassilakopoulou, Maria; Parisi, Fabio; Siddiqui, Summar; England, Allison M; Zarella, Elizabeth R; Anagnostou, Valsamo; Kluger, Yuval; Hicks, David G; Rimm, David L; Neumeister, Veronique M

2015-03-01

Individualized targeted therapies for cancer patients require accurate and reproducible assessment of biomarkers to be able to plan treatment accordingly. Recent studies have shown highly variable effects of preanalytical variables on gene expression profiling and protein levels of different tissue types. Several publications have described protein degradation of tissue samples as a direct result of delay of formalin fixation of the tissue. Phosphorylated proteins are more labile and epitope degradation can happen within 30 min of cold ischemic time. To address this issue, we evaluated the change in antigenicity of a series of phosphoproteins in paraffin-embedded samples from breast tumors as a function of time to formalin fixation. A tissue microarray consisting of 93 breast cancer specimens with documented time-to-fixation was used to evaluate changes in antigenicity of 12 phosphoepitopes frequently used in research settings as a function of cold ischemic time. Analysis was performed in a quantitative manner using the AQUA technology for quantitative immunofluorescence. For each marker, least squares univariate linear regression was performed and confidence intervals were computed using bootstrapping. The majority of the epitopes tested revealed changes in expression levels with increasing time to formalin fixation. Some phosphorylated proteins, such as phospho-HSP27 and phospho-S6 RP, involved in post-translational modification and stress response pathways increased in expression or phosphorylation levels. Others (like phospho-AKT, phosphor-ERK1/2, phospho-Tyrosine, phospho-MET, and others) are quite labile and loss of antigenicity can be reported within 1-2 h of cold ischemic time. Therefore specimen collection should be closely monitored and subjected to quality control measures to ensure accurate measurement of these epitopes. However, a few phosphoepitopes (like phospho-JAK2 and phospho-ER) are sufficiently robust for routine usage in companion diagnostic testing.

Optimization of analytical and pre-analytical conditions for MALDI-TOF-MS human urine protein profiles.

PubMed

Calvano, C D; Aresta, A; Iacovone, M; De Benedetto, G E; Zambonin, C G; Battaglia, M; Ditonno, P; Rutigliano, M; Bettocchi, C

2010-03-11

Protein analysis in biological fluids, such as urine, by means of mass spectrometry (MS) still suffers for insufficient standardization in protocols for sample collection, storage and preparation. In this work, the influence of these variables on healthy donors human urine protein profiling performed by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was studied. A screening of various urine sample pre-treatment procedures and different sample deposition approaches on the MALDI target was performed. The influence of urine samples storage time and temperature on spectral profiles was evaluated by means of principal component analysis (PCA). The whole optimized procedure was eventually applied to the MALDI-TOF-MS analysis of human urine samples taken from prostate cancer patients. The best results in terms of detected ions number and abundance in the MS spectra were obtained by using home-made microcolumns packed with hydrophilic-lipophilic balance (HLB) resin as sample pre-treatment method; this procedure was also less expensive and suitable for high throughput analyses. Afterwards, the spin coating approach for sample deposition on the MALDI target plate was optimized, obtaining homogenous and reproducible spots. Then, PCA indicated that low storage temperatures of acidified and centrifuged samples, together with short handling time, allowed to obtain reproducible profiles without artifacts contribution due to experimental conditions. Finally, interesting differences were found by comparing the MALDI-TOF-MS protein profiles of pooled urine samples of healthy donors and prostate cancer patients. The results showed that analytical and pre-analytical variables are crucial for the success of urine analysis, to obtain meaningful and reproducible data, even if the intra-patient variability is very difficult to avoid. It has been proven how pooled urine samples can be an interesting way to make easier the comparison between healthy and pathological samples and to individuate possible differences in the protein expression between the two sets of samples. Copyright 2009 Elsevier B.V. All rights reserved.

Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in Acute Coronary Syndrome: Expert Opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine.

PubMed

Wu, Alan H B; Christenson, Robert H; Greene, Dina N; Jaffe, Allan S; Kavsak, Peter A; Ordonez-Llanos, Jordi; Apple, Fred S

2018-04-01

This document is an essential companion to the third iteration of the National Academy of Clinical Biochemistry [NACB, 8 now the American Association for Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG) on cardiac markers. The expert consensus recommendations were drafted in collaboration with the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF-CB). We determined that there is sufficient clinical guidance on the use of cardiac troponin (cTn) testing from clinical practice groups. Thus, in this expert consensus document, we focused on clinical laboratory practice recommendations for high-sensitivity (hs)-cTn assays. This document utilized the expert opinion class of evidence to focus on the following 10 topics: ( a ) quality control (QC) utilization, ( b ) validation of the lower reportable analytical limits, ( c ) units to be used in reporting measurable concentrations for patients and QC materials, ( d ) 99th percentile sex-specific upper reference limits to define the reference interval; ( e ) criteria required to define hs-cTn assays, ( f ) communication with clinicians and the laboratory's role in educating clinicians regarding the influence of preanalytic and analytic problems that can confound assay results, ( g ) studies on hs-cTn assays and how authors need to document preanalytical and analytical variables, ( h ) harmonizing and standardizing assay results and the role of commutable materials, ( i ) time to reporting of results from sample receipt and sample collection, and ( j ) changes in hs-cTn concentrations over time and the role of both analytical and biological variabilities in interpreting results of serial blood collections. © 2017 American Association for Clinical Chemistry.

A method to solubilise protein aggregates for immunoassay quantification which overcomes the neurofilament "hook" effect.

PubMed

Lu, Ching-Hua; Kalmar, Bernadett; Malaspina, Andrea; Greensmith, Linda; Petzold, Axel

2011-02-15

Neurofilament (Nf) aggregates are a common pathological feature of neurodegenerative disorders. Although Nf levels have been investigated as a potential disease biomarker, Nf aggregates may mask Nf epitopes, preventing accurate quantification by immunoassay. Using the SOD1(G93A) mouse model of amyotrophic lateral sclerosis, we developed a method to disrupt Nf aggregates, allowing optimal immunoassay performance. Phosphorylated (NfH(SMI35)) and hyperphosphorylated (NfH(SMI34)) Nf levels in plasma from 120-day SOD1(G93A) mice were quantified using an in-house ELISA modified for use with small volumes. Different pre-analytical methods were tested for their ability to solubilize Nf aggregates and immunoblotting was used for qualitative analysis. A 'hook effect' was observed for serially diluted plasma samples quantified using an ELISA originally developed for CSF samples. Immunoblotting confirmed the existence of high molecular-weight NfH aggregates in plasma and the resolving effect of timed urea on these aggregates. Thermostatic (pre-thawing) and chemical (calcium chelators, urea) pre-analytical processing of samples had variable success in disrupting NfH aggregates. Timed urea-calcium chelator incubation yielded the most consistent plasma NfH levels. A one hour sample pre-incubation with 0.5M urea in Barbitone-EDTA buffer at room temperature resolved the "hook effect" without compromising the ELISA. In SOD1(G93A) mice, median levels of NfH(SMI34) were over 10-fold and NfH(SMI35) levels 5-fold greater than controls. NfH aggregates can be solubilised and the "hook effect" abolished by a one-hour sample pre-incubation in a urea-calcium chelator-enriched buffer. This method is applicable for quantification of NfH phosphoforms in experimental and disease settings where Nf aggregate formation occurs. © 2010 Elsevier B.V. All rights reserved.

A new approach to standardize multicenter studies: mobile lab technology for the German Environmental Specimen Bank.

PubMed

Lermen, Dominik; Schmitt, Daniel; Bartel-Steinbach, Martina; Schröter-Kermani, Christa; Kolossa-Gehring, Marike; von Briesen, Hagen; Zimmermann, Heiko

2014-01-01

Technical progress has simplified tasks in lab diagnosis and improved quality of test results. Errors occurring during the pre-analytical phase have more negative impact on the quality of test results than errors encountered during the total analytical process. Different infrastructures of sampling sites can highly influence the quality of samples and therewith of analytical results. Annually the German Environmental Specimen Bank (ESB) collects, characterizes, and stores blood, plasma, and urine samples of 120-150 volunteers each on four different sampling sites in Germany. Overarching goal is to investigate the exposure to environmental pollutants of non-occupational exposed young adults combining human biomonitoring with questionnaire data. We investigated the requirements of the study and the possibility to realize a highly standardized sampling procedure on a mobile platform in order to increase the required quality of the pre-analytical phase. The results lead to the development of a mobile epidemiologic laboratory (epiLab) in the project "Labor der Zukunft" (future's lab technology). This laboratory includes a 14.7 m(2) reception area to record medical history and exposure-relevant behavior, a 21.1 m(2) examination room to record dental fillings and for blood withdrawal, a 15.5 m(2) biological safety level 2 laboratory to process and analyze samples on site including a 2.8 m(2) personnel lock and a 3.6 m2 cryofacility to immediately freeze samples. Frozen samples can be transferred to their final destination within the vehicle without breaking the cold chain. To our knowledge, we herewith describe for the first time the implementation of a biological safety laboratory (BSL) 2 lab and an epidemiologic unit on a single mobile platform. Since 2013 we have been collecting up to 15.000 individual human samples annually under highly standardized conditions using the mobile laboratory. Characterized and free of alterations they are kept ready for retrospective analyses in their final archive, the German ESB.

Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche.

PubMed

Zhang, Wenting; Gu, Yexin; Sun, Qiaoling; Siegel, David S; Tolias, Peter; Yang, Zheng; Lee, Woo Y; Zilberberg, Jenny

2015-01-01

We previously reported a new approach for culturing difficult-to-preserve primary patient-derived multiple myeloma cells (MMC) using an osteoblast (OSB)-derived 3D tissue scaffold constructed in a perfused microfluidic environment and a culture medium supplemented with patient plasma. In the current study, we used this biomimetic model to show, for the first time, that the long-term survival of OSB is the most critical factor in maintaining the ex vivo viability and proliferative capacity of MMC. We found that the adhesion and retention of MMC to the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC and patient plasma, the viability and osteogenic activity of OSB became gradually compromised, and consequently MMC could not remain viable over 3 weeks. We demonstrated that the long-term survival of both OSB and MMC could be enhanced by: (1) optimizing perfusion flow rate and patient-derived plasma composition in the culture medium and (2) replenishing OSB during culture as a practical means of prolonging MMC's viability beyond several weeks. These findings were obtained using a high-throughput well plate-based perfusion device from the perspective of optimizing the ex vivo preservation of patient-derived MM biospecimens for downstream use in biological studies and chemosensitivity analyses.

Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche

PubMed Central

Zhang, Wenting; Gu, Yexin; Sun, Qiaoling; Siegel, David S.; Tolias, Peter; Yang, Zheng

2015-01-01

We previously reported a new approach for culturing difficult-to-preserve primary patient-derived multiple myeloma cells (MMC) using an osteoblast (OSB)-derived 3D tissue scaffold constructed in a perfused microfluidic environment and a culture medium supplemented with patient plasma. In the current study, we used this biomimetic model to show, for the first time, that the long-term survival of OSB is the most critical factor in maintaining the ex vivo viability and proliferative capacity of MMC. We found that the adhesion and retention of MMC to the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC and patient plasma, the viability and osteogenic activity of OSB became gradually compromised, and consequently MMC could not remain viable over 3 weeks. We demonstrated that the long-term survival of both OSB and MMC could be enhanced by: (1) optimizing perfusion flow rate and patient-derived plasma composition in the culture medium and (2) replenishing OSB during culture as a practical means of prolonging MMC’s viability beyond several weeks. These findings were obtained using a high-throughput well plate-based perfusion device from the perspective of optimizing the ex vivo preservation of patient-derived MM biospecimens for downstream use in biological studies and chemosensitivity analyses. PMID:25973790

Cohort Profile: The Malaysian Cohort (TMC) project: a prospective study of non-communicable diseases in a multi-ethnic population

PubMed Central

Jamal, Rahman; Syed Zakaria, Syed Zulkifli; Kamaruddin, Mohd Arman; Abd Jalal, Nazihah; Ismail, Norliza; Mohd Kamil, Norkhamiwati; Abdullah, Noraidatulakma; Baharudin, Norhafizah; Hussin, Noor Hamidah; Othman, Hanita; Mahadi, Nor Muhammad

2015-01-01

The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The top-down approach to this population-based cohort study ensured the allocation of sufficient funding for the project which aimed to recruit 100 000 individuals aged 35–70 years. Participants were recruited from rural and urban areas as well as from various socioeconomic groups. The main objectives of the study were to identify risk factors, to study gene-environment interaction and to discover biomarkers for the early detection of cancers and other diseases. At recruitment, a questionnaire-based interview was conducted, biophysical measurements were performed and biospecimens were collected, processed and stored. Baseline investigations included fasting blood sugar, fasting lipid profile, renal profile and full blood count. From April 2006 to the end of September 2012 we recruited a total of 106 527participants. The baseline prevalence data showed 16.6% participants with diabetes, 46.5% with hypertension, 44.9% with hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in June 2013. This is the most comprehensive and biggest cohort study in Malaysia, and has become a valuable resource for epidemiological and biological research. For information on collaboration and also data access, investigators can contact the project leader at (rahmanj@ppukm.ukm.edu.my). PMID:24729425

Public Preferences Regarding Informed Consent Models for Participation in Population-based Genomic Research

PubMed Central

Platt, Jodyn; Bollinger, Juli; Dvoskin, Rachel; Kardia, Sharon LR; Kaufman, David

2013-01-01

Purpose Some large population biobanks that house biospecimens and health information for research seek broad consent from participants, while others re-consent for specific new studies. Understanding research participants’ attitudes and preferences about broad and narrow consent may improve recruitment, retention, and public support. Methods An online survey was conducted among a representative sample of 4,659 US adults to examine relationships between consent preferences and demographic factors, beliefs about privacy, the value of research, and the perceived trustworthiness of researchers. Results Participants preferred broad consent (52%) over study-by-study consent models (48%). Higher preferences for study-by-study consent observed among Black non-Hispanic respondents, and respondents with lower income and education were explained by differences in the prevalence of one or more beliefs about the study. Respondents with fears about research and those that would feel respected if asked for permission for each research use preferred study-by-study consent. Preference for broad consent was related to the desire not to be bothered with multiple requests and the belief that the study could lead to improved treatments, cures, and lives saved. Conclusion These data suggest that support for broad consent is contingent on sufficient information about data use. Work with research participants and community leaders to understand, respond to, and influence opinions about a given, ongoing study may improve uptake of broad consent. PMID:23660530

Cohort Profile: The Malaysian Cohort (TMC) project: a prospective study of non-communicable diseases in a multi-ethnic population.

PubMed

Jamal, Rahman; Syed Zakaria, Syed Zulkifli; Kamaruddin, Mohd Arman; Abd Jalal, Nazihah; Ismail, Norliza; Mohd Kamil, Norkhamiwati; Abdullah, Noraidatulakma; Baharudin, Norhafizah; Hussin, Noor Hamidah; Othman, Hanita; Mahadi, Nor Muhammad

2015-04-01

The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The top-down approach to this population-based cohort study ensured the allocation of sufficient funding for the project which aimed to recruit 100,000 individuals aged 35-70 years. Participants were recruited from rural and urban areas as well as from various socioeconomic groups. The main objectives of the study were to identify risk factors, to study gene-environment interaction and to discover biomarkers for the early detection of cancers and other diseases. At recruitment, a questionnaire-based interview was conducted, biophysical measurements were performed and biospecimens were collected, processed and stored. Baseline investigations included fasting blood sugar, fasting lipid profile, renal profile and full blood count. From April 2006 to the end of September 2012 we recruited a total of 106,527 participants. The baseline prevalence data showed 16.6% participants with diabetes, 46.5% with hypertension, 44.9% with hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in June 2013. This is the most comprehensive and biggest cohort study in Malaysia, and has become a valuable resource for epidemiological and biological research. For information on collaboration and also data access, investigators can contact the project leader at (rahmanj@ppukm.ukm.edu.my). © The Author 2014. Published by Oxford University Press on behalf of the International Epidemiological Association.

A review of international biobanks and networks: success factors and key benchmarks.

PubMed

Vaught, Jim; Kelly, Andrea; Hewitt, Robert

2009-09-01

Biobanks and biobanking networks are involved in varying degrees in the collection, processing, storage, and dissemination of biological specimens. This review outlines the approaches that 16 of the largest biobanks and biobanking networks in Europe, North America, Australia, and Asia have taken to collecting and distributing human research specimens and managing scientific initiatives while covering operating costs. Many are small operations that exist as either a single or a few freezers in a research laboratory, hospital clinical laboratory, or pathology suite. Larger academic and commercial biobanks operate to support large clinical and epidemiological studies. Operational and business models depend on the medical and research missions of their institutions and home countries. Some national biobanks operate with a centralized physical biobank that accepts samples from multiple locations. Others operate under a "federated" model where each institution maintains its own collections but agrees to list them on a central shared database. Some collections are "project-driven" meaning that specimens are collected and distributed to answer specific research questions. "General" collections are those that exist to establish a reference collection, that is, not to meet particular research goals but to be available to respond to multiple requests for an assortment of research uses. These individual and networked biobanking systems operate under a variety of business models, usually incorporating some form of partial cost recovery, while requiring at least partial public or government funding. Each has a well-defined biospecimen-access policy in place that specifies requirements that must be met-such as ethical clearance and the expertise to perform the proposed experiments-to obtain samples for research. The success of all of these biobanking models depends on a variety of factors including well-defined goals, a solid business plan, and specimen collections that are developed according to strict quality and operational controls.

Dietary Fiber Intake Is Associated with HbA1c Level among Prevalent Patients with Type 2 Diabetes in Pudong New Area of Shanghai, China

PubMed Central

Jiang, Junyi; Qiu, Hua; Zhao, Genming; Zhou, Yi; Zhang, Zhijie; Zhang, Hong; Jiang, Qingwu; Sun, Qiao; Wu, Hongyan; Yang, Liming; Ruan, Xiaonan; Xu, Wang-Hong

2012-01-01

Background Dietary factors play an important role in glycemic control in diabetic patients. However, little is known about their effects among Chinese diabetic patients, whose diets are typically abundant in fiber and high in glycemic index (GI) values. Methodology/Principal Findings 934 patients with type 2 diabetes and 918 healthy volunteers from Pudong New Area, Shanghai, China, were interviewed during the period of Oct-Dec, 2006 to elicit demographic characteristics and lifestyle factors. Dietary habits were assessed using a validated food frequency questionnaire. Anthropometric measurements, bio-specimen collection and biochemical assays were conducted at the interview according to a standard protocol. In this population, diabetic patients consumed lower levels of energy and macronutrients but had higher levels of fasting plasma glucose (FPG), glycolated hemoglobin A1c (HbA1c), triglyceride and body mass index than healthy adults. While the average consumption levels of the nutrients among diabetic patients did not vary along duration of the disease, the average levels of FPG and HbA1c increased with increasing duration. Regardless of diabetes duration, HbA1c level was observed lower in patients having a higher fiber or lower GI intake. Compared with those with the lowest tertile intake of fiber, the adjusted odds ratios (ORs) for poor glycemic control reduced from 0.75 (95%CI: 0.54–1.06) to 0.51 (95%CI: 0.34–0.75) with increasing tertile intake (P for trend <0.001). Conclusions Dietary fiber may play an important role in reducing HbA1c level. Increasing fiber intake may be an effective approach to improve glycemic control among Chinese diabetic patients. PMID:23077514

Pregnancy as a Window to Future Cardiovascular Health: Design and Implementation of the nuMoM2b Heart Health Study

PubMed Central

Haas, David M; Ehrenthal, Deborah B; Koch, Matthew A; Catov, Janet M; Barnes, Shannon E; Facco, Francesca; Parker, Corette B; Mercer, Brian M; Bairey-Merz, C Noel; Silver, Robert M; Wapner, Ronald J; Simhan, Hyagriv N; Hoffman, Matthew K; Grobman, William A; Greenland, Philip; Wing, Deborah A; Saade, George R; Parry, Samuel; Zee, Phyllis C; Reddy, Uma M; Pemberton, Victoria L; Burwen, Dale R

2016-01-01

Abstract The National Institute of Child Health and Human Development's Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study (HHS) was designed to investigate the relationships between adverse pregnancy outcomes and modifiable risk factors for cardiovascular disease. The ongoing nuMoM2b-HHS, which started in 2013, is a prospective follow-up of the nuMoM2b cohort, which included 10,038 women recruited between 2010 and 2013 from 8 centers across the United States who were initially observed over the course of their first pregnancies. In this report, we detail the design and study procedures of the nuMoM2b-HHS. Women in the pregnancy cohort who consented to be contacted for participation in future studies were approached at 6-month intervals to ascertain health information and to maintain ongoing contact. Two to 5 years after completion of the pregnancy documented in the nuMoM2b, women in the nuMoM2b-HHS were invited to an in-person study visit. During this visit, they completed psychosocial and medical history questionnaires and had clinical measurements and biological specimens obtained. A subcohort of participants who had objective assessments of sleep-disordered breathing during pregnancy were asked to repeat this investigation. This unique prospective observational study includes a large, geographically and ethnically diverse cohort, rich depth of phenotypic information about adverse pregnancy outcomes, and clinical data and biospecimens from early in the index pregnancy onward. Data obtained from this cohort will provide mechanistic and clinical insights into how data on a first pregnancy can provide information about the potential development of subsequent risk factors for cardiovascular disease. PMID:26825925

Incorporating Salivary Biomarkers into Nursing Research: An Overview and Review of Best Practices

PubMed Central

Granger, Douglas A.; Johnson, Sara B.; Szanton, Sarah L.; Out, Dorothée; Schumann, Lynette Lau

2014-01-01

Analytes and biomarkers present in saliva may provide insight into individual differences in environmental chemical exposures, variation in reproductive hormones, therapeutic and illegal substance use, changes in stress-related physiology, and the immunologic footprints of infectious disease. The wealth of information provided by salivary analytes has the potential to enrich biobehavioral nursing research by enabling researchers to measure these individual differences in the clinic as well as in patients' and participants' everyday social worlds. In this paper we provide a roadmap for researchers new to this area who would like to learn more about integrating salivary biospecimens into the next generation of health research. In addition, we highlight best practices and strategies to avoid common pitfalls for researchers already engaged in this field. PMID:22593229

An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray.

PubMed

Salas, Lucas A; Koestler, Devin C; Butler, Rondi A; Hansen, Helen M; Wiencke, John K; Kelsey, Karl T; Christensen, Brock C

2018-05-29

Genome-wide methylation arrays are powerful tools for assessing cell composition of complex mixtures. We compare three approaches to select reference libraries for deconvoluting neutrophil, monocyte, B-lymphocyte, natural killer, and CD4+ and CD8+ T-cell fractions based on blood-derived DNA methylation signatures assayed using the Illumina HumanMethylationEPIC array. The IDOL algorithm identifies a library of 450 CpGs, resulting in an average R 2  = 99.2 across cell types when applied to EPIC methylation data collected on artificial mixtures constructed from the above cell types. Of the 450 CpGs, 69% are unique to EPIC. This library has the potential to reduce unintended technical differences across array platforms.

Ongoing Use of Data and Specimens from NCI Sponsored Cancer Prevention Clinical Trials in the Community Clinical Oncology Program

PubMed Central

Minasian, Lori; Tangen, Catherine M.; Wickerham, D. Lawrence

2015-01-01

Large cancer prevention trials provide opportunities to collect a wide array of data and biospecimens at study entry and longitudinally, for a healthy, aging population without cancer. This provides an opportunity to use pre-diagnostic data and specimens to evaluate hypotheses about the initial development of cancer. This paper reports on strides made by, and future possibilities for, the use of accessible biorepositories developed from precisely annotated samples obtained through large-scale National Cancer Institute (NCI)-sponsored cancer prevention clinical trials conducted by the NCI Cooperative Groups. These large cancer prevention studies, which have enrolled over 80,000 volunteers, continue to contribute to our understanding of cancer development more than 10 years after they were closed. PMID:26433556

Nanoplatforms for highly sensitive fluorescence detection of cancer-related proteases.

PubMed

Wang, Hongwang; Udukala, Dinusha N; Samarakoon, Thilani N; Basel, Matthew T; Kalita, Mausam; Abayaweera, Gayani; Manawadu, Harshi; Malalasekera, Aruni; Robinson, Colette; Villanueva, David; Maynez, Pamela; Bossmann, Leonie; Riedy, Elizabeth; Barriga, Jenny; Wang, Ni; Li, Ping; Higgins, Daniel A; Zhu, Gaohong; Troyer, Deryl L; Bossmann, Stefan H

2014-02-01

Numerous proteases are known to be necessary for cancer development and progression including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins. The goal of this research is to develop an Fe/Fe3O4 nanoparticle-based system for clinical diagnostics, which has the potential to measure the activity of cancer-associated proteases in biospecimens. Nanoparticle-based "light switches" for measuring protease activity consist of fluorescent cyanine dyes and porphyrins that are attached to Fe/Fe3O4 nanoparticles via consensus sequences. These consensus sequences can be cleaved in the presence of the correct protease, thus releasing a fluorescent dye from the Fe/Fe3O4 nanoparticle, resulting in highly sensitive (down to 1 × 10(-16) mol l(-1) for 12 proteases), selective, and fast nanoplatforms (required time: 60 min).

Selecting a Laboratory Information Management System for Biorepositories in Low- and Middle-Income Countries: The H3Africa Experience and Lessons Learned

PubMed Central

Musinguzi, Henry; Lwanga, Newton; Kezimbira, Dafala; Kigozi, Edgar; Katabazi, Fred Ashaba; Wayengera, Misaki; Joloba, Moses Lutaakome; Abayomi, Emmanuel Akin; Swanepoel, Carmen; Croxton, Talishiea; Ozumba, Petronilla; Thankgod, Anazodo; van Zyl, Lizelle; Mayne, Elizabeth Sarah; Kader, Mukthar; Swartz, Garth

2017-01-01

Biorepositories in Africa need significant infrastructural support to meet International Society for Biological and Environmental Repositories (ISBER) Best Practices to support population-based genomics research. ISBER recommends a biorepository information management system which can manage workflows from biospecimen receipt to distribution. The H3Africa Initiative set out to develop regional African biorepositories where Uganda, Nigeria, and South Africa were successfully awarded grants to develop the state-of-the-art biorepositories. The biorepositories carried out an elaborate process to evaluate and choose a laboratory information management system (LIMS) with the aim of integrating the three geographically distinct sites. In this article, we review the processes, African experience, lessons learned, and make recommendations for choosing a biorepository LIMS in the African context.

Pooling biomarker data from different studies of disease risk, with a focus on endogenous hormones

PubMed Central

Key, Timothy J; Appleby, Paul N; Allen, Naomi E; Reeves, Gillian K

2010-01-01

Large numbers of observations are needed to provide adequate power in epidemiological studies of biomarkers and cancer risk. However, there are currently few large mature studies with adequate numbers of cases with biospecimens available. Therefore pooling biomarker measures from different studies is a valuable approach, enabling investigators to make robust estimates of risk and to examine associations in subgroups of the population. The ideal situation is to have standardized methods in all studies so that the biomarker data can be pooled in their original units. However, even when the studies do not have standardized methods, as with existing studies on hormones and cancer, a simple approach using study-specific quantiles or percentage increases can provide substantial information on the relationship of the biomarker with cancer risk. PMID:20233851

Hematological reference values of healthy Malaysian population.

PubMed

Roshan, T M; Rosline, H; Ahmed, S A; Rapiaah, M; Wan Zaidah, A; Khattak, M N

2009-10-01

Health and disease can only be distinguished by accurate and reliable reference values of a particular laboratory test. It is now a proven fact that there is considerable variation in hematology reference intervals depending on the demographic and preanalytical variables. There are evidences that values provided by manufacturers do not have appropriate application for all populations. Moreover, reference ranges provided by different laboratory manuals and books also do not solve this problem. We are presenting here normal reference ranges of Malaysian population. These values were determined by using Sysmex XE-2100 and ACL 9000 hematology and coagulation analyzers. Results from this study showed that there were considerable differences in the reference values from manufacturers, western population or laboratory manuals compared with those from the local population.

Clinical patient registry recruitment and retention: a survey of patients in two chronic disease registries.

PubMed

Solomon, Daniel H; Shadick, Nancy A; Weinblatt, Michael E; Frits, Michelle; Iannaccone, Christine; Zak, Agnes; Korzenik, Joshua R

2017-04-17

The collection of routine clinical data in the setting of research registries can serve an important role in understanding real world care. However, relatively little is known about the patient experience in registries, motivating us to survey patients enrolled in two chronic disease registries. We conducted similar surveys in two disease-based registries based at one academic medical center in the US. One group of patients with rheumatoid arthritis (RA) had been enrolled in a registry, and we focused on retention factors. In a second group of patients with inflammatory bowel disease (IBD) recently enrolled or considering enrollment, we examined factors that would influence their enrollment and willingness to answer frequent questionnaires and give biospecimens. The surveys were analyzed using descriptive statistics and the two cohorts were compared using nonparametric and chi-square tests. We received 150 (50%) completed surveys from RA and 169 (63%) from IBD patients. Mean age of subjects was 62 years in RA and 43 in IBD with more women respondents with RA (83%) than IBD (62%). The two groups described very similar factors as the top three motivations for participation: desire to help others, desire to improve care of own disease, and ease of volunteering. Preferred methods of surveying included mail, e-mail, but telephone was not favored; age was an important correlate of this preference. Respondents preferred surveys either every 1-3 months (28.7% RA and 55.0% IBD) or every 4-6 months (50.7% RA and 29.0% IBD). They differed in the preference for payment for answering surveys with 68.0% with RA answering that no payment was necessary but only 36.1% with IBD felt similarly. Patients engaged in clinical registries demonstrate a high level of commitment to improve care and many report a willingness to answer questions relatively frequently.

An analysis of the impact of pre-analytical factors on the urine proteome: Sample processing time, temperature, and proteolysis.

PubMed

Hepburn, Sophie; Cairns, David A; Jackson, David; Craven, Rachel A; Riley, Beverley; Hutchinson, Michelle; Wood, Steven; Smith, Matthew Welberry; Thompson, Douglas; Banks, Rosamonde E

2015-06-01

We have examined the impact of sample processing time delay, temperature, and the addition of protease inhibitors (PIs) on the urinary proteome and peptidome, an important aspect of biomarker studies. Ten urine samples from patients with varying pathologies were each divided and PIs added to one-half, with aliquots of each then processed and frozen immediately, or after a delay of 6 h at 4°C or room temperature (20-22°C), effectively yielding 60 samples in total. Samples were then analyzed by 2D-PAGE, SELDI-TOF-MS, and immunoassay. Interindividual variability in profiles was the dominant feature in all analyses. Minimal changes were observed by 2D-PAGE as a result of delay in processing, temperature, or PIs and no changes were seen in IgG, albumin, β2 -microglobulin, or α1 -microglobulin measured by immunoassay. Analysis of peptides showed clustering of some samples by presence/absence of PIs but the extent was very patient-dependent with most samples showing minimal effects. The extent of processing-induced changes and the benefit of PI addition are patient- and sample-dependent. A consistent processing methodology is essential within a study to avoid any confounding of the results. © 2014 The Authors PROTEOMICS Clinical Applications Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Connecting thermodynamics and economics: well-lit roads and burned bridges.

PubMed

Glucina, Mark David; Mayumi, Kozo

2010-01-01

Almost 40 years have passed since Georgescu-Roegen's seminal work, The Entropy Law and the Economic Process. During this time there has been much debate on the relevance of thermodynamics to economics, and many attempts to build bridges between the two. There has also been much confusion as to what the laws of thermodynamics actually say. This article clearly explains heat, work, and the thermodynamic laws, the meaning of entropy, and the importance of kinetics as a barrier to thermodynamically favorable processes. The two most important misunderstandings in the literature, namely entropy as disorder, and entropy as a measure of information, are highlighted. Reviewing the literature shows that thermodynamics is most relevant for building a descriptive model, or preanalytic vision of economics, because it implies physical constraints on production and consumption. Similarly, it suggests that there may be serious flaws with neoclassical economic models, and in particular the primacy of sustained growth. However, thermodynamics does not seem to aid mathematical modeling in economics, nor does it provide normative insights. As an aid to energy policy, thermodynamics is useful for assessing the feasibility of technology options--those that have the potential to meet our goals, and should be counted as options, and those that should not. But it does not provide a prescription outside of this technical realm. Factors, such as environmental impact, cost, and social acceptability, will ultimately determine which technically feasible options are most desirable.

Metabolomic analysis-Addressing NMR and LC-MS related problems in human feces sample preparation.

PubMed

Moosmang, Simon; Pitscheider, Maria; Sturm, Sonja; Seger, Christoph; Tilg, Herbert; Halabalaki, Maria; Stuppner, Hermann

2017-10-31

Metabolomics is a well-established field in fundamental clinical research with applications in different human body fluids. However, metabolomic investigations in feces are currently an emerging field. Fecal sample preparation is a demanding task due to high complexity and heterogeneity of the matrix. To gain access to the information enclosed in human feces it is necessary to extract the metabolites and make them accessible to analytical platforms like NMR or LC-MS. In this study different pre-analytical parameters and factors were investigated i.e. water content, different extraction solvents, influence of freeze-drying and homogenization, ratios of sample weight to extraction solvent, and their respective impact on metabolite profiles acquired by NMR and LC-MS. The results indicate that profiles are strongly biased by selection of extraction solvent or drying of samples, which causes different metabolites to be lost, under- or overstated. Additionally signal intensity and reproducibility of the measurement were found to be strongly dependent on sample pre-treatment steps: freeze-drying and homogenization lead to improved release of metabolites and thus increased signals, but at the same time induced variations and thus deteriorated reproducibility. We established the first protocol for extraction of human fecal samples and subsequent measurement with both complementary techniques NMR and LC-MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Moving-Boundary Problems Associated with Lyopreservation

NASA Astrophysics Data System (ADS)

Gruber, Christopher Andrew

The work presented in this Dissertation is motivated by research into the preservation of biological specimens by way of vitrification, a technique known as lyopreservation. The operative principle behind lyopreservation is that a glassy material forms as a solution of sugar and water is desiccated. The microstructure of this glass impedes transport within the material, thereby slowing metabolism and effectively halting the aging processes in a biospecimen. This Dissertation is divided into two segments. The first concerns the nature of diffusive transport within a glassy state. Experimental studies suggest that diffusion within a glass is anomalously slow. Scaled Brownian motion (SBM) is proposed as a mathematical model which captures the qualitative features of anomalously slow diffusion while minimizing computational expense. This model is applied to several moving-boundary problems and the results are compared to a more well-established model, fractional anomalous diffusion (FAD). The virtues of SBM are based on the model's relative mathematical simplicity: the governing equation under FAD dynamics involves a fractional derivative operator, which precludes the use of analytical methods in almost all circumstances and also entails great computational expense. In some geometries, SBM allows similarity solutions, though computational methods are generally required. The use of SBM as an approximation to FAD when a system is "nearly classical'' is also explored. The second portion of this Dissertation concerns spin-drying, which is an experimental approach to biopreservation in a laboratory setting. A biospecimen is adhered to a glass wafer and this substrate is covered with sugar solution and rapidly spun on a turntable while water is evaporated from the film surface. The mathematical model for the spin-drying process includes diffusion, viscous fluid flow, and evaporation, among other contributions to the dynamics. Lubrication theory is applied to the model and an expansion in orthogonal polynomials is applied. The resulting system of equations is solved computationally. The influence of various experimental parameters upon the system dynamics is investigated, particularly the role of the spin rate. A convergence study of the solution verifies that the polynomial expansion method yields accurate results.

DRAQ5 and Eosin (‘D&E’) as an Analog to Hematoxylin and Eosin for Rapid Fluorescence Histology of Fresh Tissues

PubMed Central

Elfer, Katherine N.; Sholl, Andrew B.; Wang, Mei; Tulman, David B.; Mandava, Sree H.; Lee, Benjamin R.; Brown, J. Quincy

2016-01-01

Real-time on-site histopathology review of biopsy tissues at the point-of-procedure has great potential for significant clinical value and improved patient care. For instance, on-site review can aid in rapid screening of diagnostic biopsies to reduce false-negative results, or in quantitative assessment of biospecimen quality to increase the efficacy of downstream laboratory and histopathology analysis. However, the only currently available rapid pathology method, frozen section analysis (FSA), is too time- and labor-intensive for use in screening large quantities of biopsy tissues and is too destructive for maximum tissue conservation in multiple small needle core biopsies. In this work we demonstrate the spectrally-compatible combination of the nuclear stain DRAQ5 and the anionic counterstain eosin as a dual-component fluorescent staining analog to hematoxylin and eosin intended for use on fresh, unsectioned tissues. Combined with optical sectioning fluorescence microscopy and pseudo-coloring algorithms, DRAQ5 and eosin (“D&E”) enables very fast, non-destructive psuedohistological imaging of tissues at the point-of-acquisition with minimal tissue handling and processing. D&E was validated against H&E on a one-to-one basis on formalin-fixed paraffin-embedded and frozen section tissues of various human organs using standard epi-fluorescence microscopy, demonstrating high fidelity of the staining mechanism as an H&E analog. The method was then applied to fresh, whole 18G renal needle core biopsies and large needle core prostate biospecimen biopsies using fluorescence structured illumination optical sectioning microscopy. We demonstrate the ability to obtain high-resolution histology-like images of unsectioned, fresh tissues similar to subsequent H&E staining of the tissue. The application of D&E does not interfere with subsequent standard-of-care H&E staining and imaging, preserving the integrity of the tissue for thorough downstream analysis. These results indicate that this dual-stain pseudocoloring method could provide a real-time histology-like image at the time of acquisition and valuable objective tissue analysis for the clinician at the time of service. PMID:27788264