Showing papers in "Biochemia Medica in 2016"

On determining the most appropriate test cut-off value: the case of tests with continuous results

Abstract: There are several criteria for determination of the most appropriate cut-off value in a diagnostic test with continuous results. Mostly based on receiver operating characteristic (ROC) analysis, there are various methods to determine the test cut-off value. The most common criteria are the point on ROC curve where the sensitivity and specificity of the test are equal; the point on the curve with minimum distance from the left-upper corner of the unit square; and the point where the Youden's index is maximum. There are also methods mainly based on Bayesian decision analysis. Herein, we show that a proposed method that maximizes the weighted number needed to misdiagnose, an index of diagnostic test effectiveness we previously proposed, is the most appropriate technique compared to the aforementioned ones. For determination of the cut-off value, we need to know the pretest probability of the disease of interest as well as the costs incurred by misdiagnosis. This means that even for a certain diagnostic test, the cut-off value is not universal and should be determined for each region and for each disease condition.

The use of platelet indices, plateletcrit, mean platelet volume and platelet distribution width in emergency non-traumatic abdominal surgery: a systematic review.

Abstract: Platelet indices (PI) -- plateletcrit, mean platelet volume (MPV) and platelet distribution width (PDW) -- are a group of derived platelet parameters obtained as a part of the automatic complete blood count. Emerging evidence suggests that PIs may have diagnostic and prognostic value in certain diseases. This study aimed to summarize the current scientific knowledge on the potential role of PIs as a diagnostic and prognostic marker in patients having emergency, non-traumatic abdominal surgery. In December 2015, we searched Medline/PubMed, Scopus and Google Scholar to identify all articles on PIs. Overall, considerable evidence suggests that PIs are altered with acute appendicitis. Although the role of PI in the differential diagnosis of acute abdomen remains uncertain, low MPV might be useful in acute appendicitis and acute mesenteric ischemia, with high MPV predicting poor prognosis in acute mesenteric ischemia. The current lack of consistency and technical standards in studies involving PIs should be regarded as a serious limitation to comparing these studies. Further large, multicentre prospective studies concurrently collecting data from different ethnicities and genders are needed before they can be used in routine clinical practice.

Understanding the effect size and its measures

Abstract: The evidence based medicine paradigm demands scientific reliability, but modern research seems to overlook it sometimes. The power analysis represents a way to show the meaningfulness of findings, regardless to the emphasized aspect of statistical significance. Within this statistical framework, the estimation of the effect size represents a means to show the relevance of the evidences produced through research. In this regard, this paper presents and discusses the main procedures to estimate the size of an effect with respect to the specific statistical test used for hypothesis testing. Thus, this work can be seen as an introduction and a guide for the reader interested in the use of effect size estimation for its scientific endeavour.

Reference intervals: current status, recent developments and future considerations.

Abstract: Reliable and accurate reference intervals (RIs) for laboratory analyses are an integral part of the process of correct interpretation of clinical laboratory test results. RIs given in laboratory reports have an important role in aiding the clinician in interpreting test results in reference to values for healthy populations. Since the 1980s, the International Federation of Clinical Chemistry (IFCC) has been proactive in establishing recommendations to clarify the true significance of the term 'RIs, to select the appropriate reference population and statistically analyse the data. The C28-A3 guideline published by the Clinical and Laboratory Standards Institute (CLSI) and IFCC is still the most widely-used source of reference in this area. In recent years, protocols additional to the Guideline have been published by the IFCC, Committee on Reference Intervals and Decision Limits (C-RIDL), including all details of multicenter studies on RIs to meet the requirements in this area. Multicentric RIs studies are the most important development in the area of RIs. Recently, the C-RIDL has performed many multicentric studies to obtain common RIs. Confusion of RIs and clinical decision limits (CDLs) remains an issue and pediatric and geriatric age groups are a significant problem. For future studies of RIs, the genetic effect would seem to be the most challenging area. The aim of the review is to present the current theory and practice of RIs, with special emphasis given to multicenter RIs studies, RIs studies for pediatric and geriatric age groups, clinical decision limits and partitioning by genetic effects on RIs.

Phlebotomy, a bridge between laboratory and patient.

Abstract: The evidence-based paradigm has changed and evolved medical practice. Phlebotomy, which dates back to the age of ancient Greece, has gained experience through the evolution of medicine becoming a fundamental diagnostic tool. Nowadays it connects the patient with the clinical laboratory dimension building up a bridge. However, more often there is a gap between laboratory and phlebotomist that causes misunderstandings and burdens on patient safety. Therefore, the scope of this review is delivering a view of modern phlebotomy to "bridge" patient and laboratory. In this regard the paper describes devices, tools and procedures in the light of the most recent scientific findings, also discussing their impact on both quality of blood testing and patient safety. It also addresses the issues concerning medical aspect of venipuncture, like the practical approach to the superficial veins anatomy, as well as the management of the patient's compliance with the blood draw. Thereby, the clinical, technical and practical issues are treated with the same relevance throughout the entire paper.

Blood gas testing and related measurements: National recommendations on behalf of the Croatian Society of Medical Biochemistry and Laboratory Medicine.

Abstract: Blood gas analysis (BGA) is exposed to risks of errors caused by improper sampling, transport and storage conditions. The Clinical and Laboratory Standards Institute (CLSI) generated documents with recommendations for avoidance of potential errors caused by sample mishandling. Two main documents related to BGA issued by the CLSI are GP43-A4 (former H11-A4) Procedures for the collection of arterial blood specimens; approved standard – fourth edition, and C46-A2 Blood gas and pH analysis and related measurements; approved guideline – second edition. Practices related to processing of blood gas samples are not standardized in the Republic of Croatia. Each institution has its own protocol for ordering, collection and analysis of blood gases. Although many laboratories use state of the art analyzers, still many preanalytical procedures remain unchanged. The objective of the Croatian Society of Medical Biochemistry and Laboratory Medicine (CSMBLM) is to standardize the procedures for BGA based on CLSI recommendations. The Working Group for Blood Gas Testing as part of the Committee for the Scientific Professional Development of the CSMBLM prepared a set of recommended protocols for sampling, transport, storage and processing of blood gas samples based on relevant CLSI documents, relevant literature search and on the results of Croatian survey study on practices and policies in acid-base testing. Recommendations are intended for laboratory professionals and all healthcare workers involved in blood gas processing.

Comparison of Cobas 6500 and Iris IQ200 fully-automated urine analyzers to manual urine microscopy.

Abstract: Introduction Urine screening is achieved by either automated or manual microscopic analysis. The aim of the study was to compare Cobas 6500 and Iris IQ200 urine analyzers, and manual urine microscopic analysis. Materials and methods A total of 540 urine samples sent to the laboratory for chemical and sediment analysis were analyzed on Cobas 6500 and Iris IQ200 within 1 hour from sampling. One hundred and fifty three samples were found to have pathological sediment results and were subjected to manual microscopic analysis performed by laboratory staff blinded to the study. Spearman's and Gamma statistics were used for correlation analyses, and the McNemar test for the comparison of the two automated analyzers. Results The comparison of Cobas u701 to the manual method yielded the following regression equations: y = - 0.12 (95% CI: - 1.09 to 0.67) + 0.78 (95% CI: 0.65 to 0.95) x for WBC and y = 0.06 (95% CI: - 0.09 to 0.25) + 0.66 (95% CI: 0.57 to 0.73) x for RBC. The comparison of IQ200 Elite to manual method the following equations: y = 0.03 (95% CI: - 1.00 to 1.00) + 0.88 (95% CI: 0.66 to 1.00) x for WBC and y = - 0.22 (95% CI: - 0.80 to 0.20) + 0.40 (95% CI: 0.32 to 0.50) x for RBC. IQ200 Elite compared to Cobas u701 yielded the following equations: y = - 0.95 (95% CI: - 2.13 to 0.11) + 1.25 (95% CI: 1.08 to 1.44) x for WBC and y = - 1.20 (95% CI: - 1.80 to -0.30) + 0. 80 (95% CI: 0.55 to 1.00) x for RBC. Conclusions The two analyzers showed similar performances and good compatibility to manual microscopy. However, they are still inadequate in the determination of WBC, RBC, and EC in highly-pathological samples. Thus, confirmation by manual microscopic analysis may be useful.

Effectiveness of citrate buffer-fluoride mixture in Terumo tubes as an inhibitor of in vitro glycolysis.

Abstract: Introduction Glycolysis affects glucose determination in vitro. The placement of sample tubes in ice-water slurry with plasma separation within 30 minutes is recommended, or alternatively the use of a glycolysis inhibitor. The aim of our two-steps study was to evaluate which Terumo tube is best for glucose determination in routine clinical setting.

Scientific author names: errors, corrections, and identity profiles

Abstract: Authorship problems are deep-rooted in the field of science communication. Some of these relate to lack of specific journal instructions. For decades, experts in journal editing and publishing have been exploring the authorship criteria and contributions deserving either co-authorship or acknowledgment. The issue of inconsistencies of listing and abbreviating author names has come to the fore lately. There are reports on the difficulties of figuring out Chinese surnames and given names of South Indians in scholarly articles. However, it seems that problems with correct listing and abbreviating author names are global. This article presents an example of swapping second (father’s) name with surname in a ‘predatory’ journal, where numerous instances of incorrectly identifying and crediting authors passed unnoticed for the journal editors, and no correction has been published. Possible solutions are discussed in relation to identifying author profiles and adjusting editorial policies to the emerging problems. Correcting mistakes with author names post-publication and integrating with the Open Researcher and Contributor ID (ORCID) platform are among them.

A comparative evaluation of the analytical performances of Capillarys 2 Flex Piercing, Tosoh HLC-723 G8, Premier Hb9210, and Roche Cobas c501 Tina-quant Gen 2 analyzers for HbA1c determination.

Abstract: Introduction: Haemoglobin A 1c (HbA 1c ) is widely used in the management of diabetes. Therefore, the reliability and comparability among different analytical methods for its detection have become very important. Materials and methods: A comparative evaluation of the analytical performances (precision, linearity, accuracy, method comparison, and interferences including bilirubin, triglyceride, cholesterol, labile HbA 1c (LA 1c ), vitamin C, aspirin, fetal haemoglobin (HbF), and haemoglobin E (Hb E)) were performed on Capillarys 2 Flex Piercing (Capillarys 2FP) (Sebia, France), Tosoh HLC-723 G8 (Tosoh G8) (Tosoh, Japan), Premier Hb9210 (Trinity Biotech, Ireland) and Roche Cobas c501 (Roche c501) (Roche Diagnostics, Germany). Results: A good precision was shown at both low and high HbA 1c levels on all four systems, with all individual CVs below 2% (IFCC units) or 1.5% (NGSP units). Linearity analysis for each analyzer had achieved a good correlation coefficient (R 2 > 0.99) over the entire range tested. The analytical bias of the four systems against the IFCC targets was less than ± 6% (NGSP units), indicating a good accuracy. Method comparison showed a great correlation and agreement between methods. Very high levels of triglycerides and cholesterol (≥ 15.28 and ≥ 8.72 mmol/L, respectively) led to falsely low HbA 1c concentrations on Roche c501. Elevated HbF induced false HbA 1c detection on Capillarys 2FP (> 10%), Tosoh G8 (> 30%), Premier Hb9210 (> 15%), and Roche c501 (> 5%). On Tosoh G8, HbE induced an extra peak on chromatogram, and significantly lower results were reported. Conclusions: The four HbA 1c methods commonly used with commercial analyzers showed a good reliability and comparability, although some interference may falsely alter the result.

A reference interval study for common biochemical analytes in Eastern Turkey: a comparison of a reference population with laboratory data mining

Abstract: Introduction The aim of this study was to define the reference intervals (RIs) in a Turkish population living in Northeast Turkey (Erzurum) for 34 analytes using direct and indirect methods. In the present study, the regional RIs obtained were compared with other RI studies, primarily the nationwide study performed in Turkey. Materials and methods For the direct method, 435 blood samples were collected from a healthy group of females (N = 218) and males (N = 217) aged between 18 and 65 years. The sera were analysed in Ataturk University hospital laboratory using Roche reagents and analysers for 34 analytes. The data from 1,366,948 records were used to calculate the indirect RIs using a modified Bhattacharya method. Results Significant gender-related differences were observed for 17 analytes. There were also some apparent differences between RIs derived from indirect and direct methods particularly in some analytes (e.g. gamma-glutamyltransferase, creatine kinase, LDL-cholesterol and iron). The RIs derived with the direct method for some, but not all, of the analytes were generally comparable with the RIs reported in the nationwide study and other previous studies in Turkey.There were large differences between RIs derived by the direct method and the expected values shown in the kit insert (e.g. aspartate aminotransferase, total-cholesterol, HDL-cholesterol, and vitamin B12). Conclusions These data provide region-specific RIs for 34 analytes determined by the direct and indirect methods. The observed differences in RIs between previous studies could be related to nutritional status and environmental factors.

Urinary orosomucoid: Validation of an automated immune turbidimetric test and its possible clinical use

Abstract: Introduction Besides routine serum markers of inflammatory diseases, the diagnostic potential of selected urinary proteins has not been fully exploited yet. Former studies revealed that urinary orosomucoid (u-ORM) might have complementary information in inflammatory disorders. Our aim was to develop and validate a fully automated method for u-ORM measurements and to evaluate its potential clinical impact on systemic inflammatory diseases. Materials and methods A particle-enhanced immune turbidimetric assay was validated for a Cobas 8000/c502 analyzer to determine u-ORM levels. Spot urine samples from 72 healthy individuals, 28 patients with Crohn's disease and 30 septic patients were studied. Results Our assay time was 10 minutes and the detection limit of u-ORM was 0.02 mg/L. The intra- and inter-assay imprecision expressed as CV was less than 5%, and the recovery ranged between 95-103%. Within 10 to 60 years of age, a preliminary reference range for urinary orosomucoid/creatinine ratio (u-ORM/u-CREAT) was found to be 0.08 (0.01-0.24) mg/mmol [median (2.5-97.5 percentiles)]. Compared to controls, a five-fold increase of u-ORM/u-CREAT values in Crohn's disease and approximately a 240-fold increase in sepsis were observed. Conclusions We set up a fast, sensitive and precise turbidimetric approach for automated u-ORM determination. Our highly sensitive assay is ideal for routine u-ORM measurements and might be a potential novel laboratory test in the management of systemic inflammatory processes.

Evaluation of the appropriate time period between sampling and analyzing for automated urinalysis

Abstract: 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.

Misleading FT4 measurement: Assay-dependent antibody interference

Abstract: textIntroduction: Commonly used free thyroxine (FT4) immunoassays can be falsely elevated due to interference causing misinterpreted thyroid function. We present two cases with high FT4 concentrations due to antibody interference. This study’s aim was to investigate the source of the FT4 immunoassay interference and possibility of its removal by two different techniques in order to correct the discrepancy between obtained FT4 values and the patient’s clinical status. Materials and methods: Two patients presented at their general practitioners’ with elevated FT4 concentrations in combination with a normal and increased thyroid stimulating hormone (TSH) concentrations. Clinical symptoms differed between patients but did not correspond with the hyperthyroid status suggested by the laboratory results. FT4 concentrations from both patients were measured on four common commercial immunoassays and the dialysis method before and after treatment with heterophilic blocking tubes and protein A/G. Results: Removal of interfering antibodies using protein A/G resulted in normal FT4 concentrations. Conclusion: This report illustrates falsely elevated FT4 concentrations due to assay interference on the Immulite immunoassay analyser caused by heterophilic antibodies, which were eliminated by protein A/G treatment. We point out the importance of a close collaboration between doctors and the laboratory to avoid unnecessary clinical intervention.

Colorectal cancer detection in an asymptomatic population: fecal immunochemical test for hemoglobin vs. fecal M2-type pyruvate kinase.

Abstract: Introduction Screening programs for colorectal cancer (CRC) are mainly based on a first-line fecal immunochemical test for hemoglobin (FIT). Fecal M2-type pyruvate kinase (M2-PK) has been evaluated in clinical settings showing promising results for early CRC detection. However, the impact of fecal M2-PK assessment on the performance of first-round CRC screening programs is not known. We investigated whether fecal M2-PK alone or in combination with FIT may improve CRC screening efficacy in the general population.

Detection of multiple annexin autoantibodies in a patient with recurrent miscarriages, fulminant stroke and seronegative antiphospholipid syndrome.

Abstract: Anti-phospholipid syndrome (APS) is one of the main causes for recurrent miscarriages. The diagnosis of APS is based on the occurrence of clinical symptoms such as thrombotic events or obstetric complications as well as the detection of antiphospholipid antibodies directed against β2-glycoprotein I and cardiolipin, or a positive lupus anticoagulant assay. However, there is a subpopulation of patients with clinical symptoms of APS, but the lack of serological markers (seronegative APS). In addition, a large proportion of patients with unexplained recurrent miscarriages exist. These cases may be attributed, at least in part, to a seronegative APS. The presence of autoantibodies against annexins is potentially associated with APS. Here we used immunoassays and immunoblots to detect autoantibodies directed against annexin A1-5, and A8, respectively, in a patient with a seronegative APS and a history of six recurrent pregnancy losses and fulminant stroke. We found strong IgM isotype antibody reactivity directed against annexin A2 and annexin A8, and moderate to weak IgM isotype antibody reactivity directed against annexin A1, A3, and A5. Further studies will evaluate the diagnostic value of IgM isotype antibodies against annexin A1-A5, and A8 for seronegative APS and recurrent miscarriages.

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

Abstract: 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.

Laboratory-based clinical audit as a tool for continual improvement: an example from CSF chemistry turnaround time audit in a South-African teaching hospital.

Abstract: Introduction: Timeliness of laboratory results is crucial to patient care and outcome. Monitoring turnaround times (TAT), especially for emergency tests, is important to measure the effectiveness and efficiency of laboratory services. Laboratory-based clinical audits reveal opportunities for im proving quality. Our aim was to identify the most critical steps causing a high TAT for cerebrospinal fluid (CSF) chemistry analysis in our laboratory. Materials and methods: A 6-month retrospective audit was performed. The duration of each operational phase across the laboratory work flow was examined. A process-mapping audit trail of 60 randomly selected requests with a high TAT was conducted and reasons for high TAT were tested for significance. Results: A total of 1505 CSF chemistry requests were analysed. Transport of samples to the laboratory was primarily responsible for the high average TAT (median TAT = 170 minutes). Labelling accounted for most delays within the laboratory (median TAT = 71 minutes) with most delays occurring after regular work hours (P < 0.05). CSF chemistry requests without the appropriate number of CSF sample tubes were significantly associated with delays in movement of samples from the labelling area to the technologist’s work station (caused by a preference for microbiological testing prior to CSF chemistry). Conclusion: A laboratory-based clinical audit identified sample transportation, work shift periods and use of inappropriate CSF sample tubes as drivers of high TAT for CSF chemistry in our laboratory. The results of this audit will be used to change pre-analytical practices in our laboratory with the aim of improving TAT and customer satisfaction.

Indications for laboratory tests in primary care: assessment of the most frequent indications and requests with blank clinical information.

Abstract: Introduction: The aim of this work is twofold. Firstly, to study the temporal evolution in the number of laboratory requests from primary care without clinical indication, and to analyse the number of such requests before and after the implementation of an automated requesting procedure. Secondly, to investigate what are the most frequent clinical indications that prompted laboratory testing. Materials and methods: This is a retrospective observational study conducted from January 2009 to December 2015. We counted the requests without clinical question, calculated the number of such requests per total number of requests and listed the most frequent indications. Results: The number of tests requests with a blank clinical indication was significantly higher in 2009 when compared to 2015 (80% vs. 20%; P < 0.001). For every year in this 7-year period, dyslipidemia, essential hypertension and diabetes were the most prevalent diagnoses that prompted a laboratory test in primary care, accounting for more than 20% of all indications. Conclusions: The number of primary care requests without patient clinical question has decreased after the implementation of an automated requesting procedure. Disorders of lipid metabolism, essential hypertension and diabetes mellitus were the most prevalent diagnoses that prompted a laboratory test in primary care.

IMPACT Observatory: tracking the evolution of clinical trial data sharing and research integrity.

Abstract: Introduction The opening of research data is emerging thanks to the increasing possibilities of digital technology. The opening of clinical trial (CT) data is a part of this process, expected to have positive scientific, ethical, health, and economic impacts thus contributing to research integrity. The January 2016 proposal by the International Council of Medical Journal Editors triggered ample discussion about CT data sharing and reconfirmed the need for an ongoing assessment of its dynamics. The IMProving Access to Clinical Trials data (IMPACT) Observatory aims to play such a role, and assess the data sharing culture, policies, and practices of key players, the impact of their interventions on CTs, and contribute to a transformation of research. The objective of this paper is to present the IMPACT Observatory as well as share some of its preliminary findings. Materials and methods Methods include a scoping study of research, surveys, interviews, and an environmental scan of research data repositories. Results Our preliminary findings indicate that although opening of CT data has not yet been achieved, its evolution is encouraging. Initiatives by key players contribute to increasing of CT data sharing, and many barriers are shrinking or disappearing. Conclusions The major barrier is the lack of data sharing standards, from preparing data for public sharing to its curatorship, findability and access. However, experiences accumulated by sharing CT data according to "upon request" or "open" mechanisms could inform the development of such standards. The Vivli, CORBEL-ECRIN and Open Trials projects are currently working in this direction.

Automatic laboratory-based strategy to improve the diagnosis of type 2 diabetes in primary care

Abstract: Introduction To study the pre-design and success of a strategy based on the addition of hemoglobin A1c (HbA1c) in the blood samples of certain primary care patients to detect new cases of type 2 diabetes.

What's in a name? The problem of authors' names in research articles.

Abstract: When the editors of Biochemia Medica asked me to write a viewpoint on using a single name in authors’ by-line to a journal article, recently discussed on the Listserve of the World Association of Medical Editors (WAME) (1), I recalled two of my past experiences with names in research publishing. One is related to my own name and happened in 2002, when a psychiatrist from Slovenia, late Prof. Andrej Marusic, submitted a paper (2) to the Croatian Medical Journal, which I edited at that time. Our introduction was along the lines “So you are the other “Marusic A” that gets in the list of my papers on PubMed!” Indeed, I have always had troubles sorting out my articles from Andrej’s (and another Marusic A, a biochemist), especially because I also authored some psychiatry papers published during the 1991-1995 war against Croatia (and some close to biochemistry, too). Each time I need to update my bibliography or calculate my h-index, I have to go carefully over all publications retrieved with my surname and initial, and sort out my publications from those of other Marusic As. The second time I had to deal with authors’ names was when my co-authors and I studied the research output published in local journals from the countries in the WHO Eastern Mediterranean region (3). We had problems in finding articles from our study sample by using authors’ names because of differences in transcription and indexing of Arabic names in bibliographical databases. It seemed that the usual practice to index authors by surname(s) and first name(s) initials was a serious problem for complex Arabic names because the logic behind them is often very different from that for most western names. This is true not only for Arabic (4), but also Chinese (5) and even Spanish (6) names. According to the information on MEDLINE indexing processes, indexers pay special attention to indexing names, including full authors’ names instead of “last name – initials” format (7). MEDLINE also recognizes that some authors may have only a surname, which is then indexed in that field (LastName data element) (7). Listing only first names, as discussed in the WAME Listserve case (1), seems not to be an option in MEDLINE. The problems with indexing authors’ names do not stop there. There are cases where author’s names were used for purposes other than giving actual research credit. There is a famous story of Polly Matzinger, immunologist from the National Institutes of Health in the USA, and her Afghan hound Galadriel Mirkwood, who co-authored her paper published in the Journal of Experimental Medicine in 1978 (8). The rumour has it that she was blacklisted by the journal’s editor after the identity of the second author was disclosed, and the ban was lifted only after the editor’s death. Even older story is from physics, in which an American physicist, George Gamow, thought it would be amusing to add another name to the paper by himself and his then PhD student Ralph Alpher. By adding his friend, another eminent physicist, Hans Bethe, to the article, the by-line (Alpher, Bethe, Gamow) (9) turned into a play on the first three Greek letters α, β, and γ. I am sure that the PhD student was not thrilled with this game, as I am sure that the editor of the Journal of Experimental Medicine was not happy about the misuse of authorship, one of the most important elements of academic and scholarly life. What is the solution? I am not sure editors should go into fights with authors about their personal wishes for their name(s) presentation in an article by-line. They should embrace the solution already at hand – author identifier. For example, since 2013, MEDLINE has the option of adding unique author identifiers to the indexed article, such as Open Researcher and Contributor ID (ORCID), International Standard Name Identifier (ISNI), or a name from Virtual International Authority File (VIAF) (10). For biomedicine, ORCID seems to be the most common solution, and several editors have already implemented ORCID in their journals (11), and some publishers have already integrated ORCID into their publishing and indexing systems (12). It will take some time and effort for all stakeholders – authors, journals, publishers and indexing databases – to sort out how to link ORCIDs to all past publications. But the future is here, and incentives from research and academic institutions and research funding would be important for the full success in solving the current riddle of names in research publishing. After all, the value of the research we do is valued only in relation to the names we have. So it seems appropriate to end this essay with the quote on names: “Stat rosa pristina nomine; nomina nuda tenemus” (13).

Daily salivary cortisol profile: Insights from the Croatian Late Adolescence Stress Study (CLASS)

Abstract: Introduction: The aim of the study was to examine basal hypothalamic-pituitary-adrenal (HPA) axis activity and to determine associations of various co

The influence of sample freezing at -80°C for 2-12 weeks on glycated haemoglobin (HbA1c) concentration assayed by HPLC method on Bio-Rad D-10© auto-analyzer.

Abstract: Introduction The aim of the study was to evaluate the effect of a single freeze/thaw cycle on HbA1c concentrations measured by commercially available HPLC method. Materials and methods Study included 128 whole blood samples collected from diabetic patients (N = 60) and healthy volunteers (N = 68). HbA1c concentrations were measured in fresh blood samples. Then samples were frozen at - 80 °C for up to 12 weeks. HbA1c was assayed by ion-exchange HPLC method on Bio-Rad D-10® analyzer. Variables were compared using Wilcoxon and ANOVA Kruskal-Wallis tests. Bias between HbA1c measured in fresh and frozen samples was calculated. The comparability of HbA1c concentrations was assessed by Bland-Altman plot. Results Median (IQR) HbA1c concentration was 45.3 (36.6-61.2) mmol/mol for fresh and 45.3 (36.6-60.6) mmol/mol for frozen/thawed samples. No significant difference in HbA1c concentrations was found comparing fresh and frozen/thawed samples (P = 0.070) in the whole group, as well as in healthy and diabetic subjects. The median calculated bias between fresh and frozen/thawed samples was 0% in whole group and healthy subjects, and 1.19% in diabetic patients. No significant difference was found between the biases according to baseline HbA1c values (P = 0.150). The Bland-Altman plot analysis showed a positive bias of 0.4% (95% CI: - 2.8 - 3.7%), which indicates high compliance between HbA1c values and no relevant influence of sample freezing on clinical significance of HbA1c measurement. Conclusions Storage for up to 12 weeks at - 80 °C with a single freeze/thaw cycle does not affect HbA1c concentrations measured with HPLC method on Bio-Rad D-10® analyzer.

Continuous quality control of the blood sampling procedure using a structured observation scheme.

Abstract: INTRODUCTION An observational study was conducted using a structured observation scheme to assess compliance with the local phlebotomy guideline, to identify necessary focus items, and to investigate whether adherence to the phlebotomy guideline improved. MATERIALS AND METHODS The questionnaire from the EFLM Working Group for the Preanalytical Phase was adapted to local procedures. A pilot study of three months duration was conducted. Based on this, corrective actions were implemented and a follow-up study was conducted. All phlebotomists at the Department of Clinical Biochemistry and Pharmacology were observed. Three blood collections by each phlebotomist were observed at each session conducted at the phlebotomy ward and the hospital wards, respectively. Error frequencies were calculated for the phlebotomy ward and the hospital wards and for the two study phases. RESULTS A total of 126 blood drawings by 39 phlebotomists were observed in the pilot study, while 84 blood drawings by 34 phlebotomists were observed in the follow-up study. In the pilot study, the three major error items were hand hygiene (42% error), mixing of samples (22%), and order of draw (21%). Minor significant differences were found between the two settings. After focus on the major aspects, the follow-up study showed significant improvement for all three items at both settings (P < 0.01, P < 0.01, and P = 0.01, respectively). CONCLUSION Continuous quality control of the phlebotomy procedure revealed a number of items not conducted in compliance with the local phlebotomy guideline. It supported significant improvements in the adherence to the recommended phlebotomy procedures and facilitated documentation of the phlebotomy quality.

The characterization of four gene expression analysis in circulating tumor cells made by Multiplex-PCR from the AdnaTest kit on the lab-on-a-chip Agilent DNA 1000 platform.

Abstract: Introduction Nowadays, on-a-chip capillary electrophoresis is a routine method for the detection of PCR fragments. The Agilent 2100 Bioanalyzer was one of the first commercial devices in this field. Our project was designed to study the characteristics of Agilent DNA 1000 kit in PCR fragment analysis as a part of circulating tumour cell (CTC) detection technique. Despite the common use of this kit a complex analysis of the results from a long-term project is still missing. Materials and methods A commercially available Agilent DNA 1000 kit was used as a final step in the CTC detection (AdnaTest) for the determination of the presence of PCR fragments generated by Multiplex PCR. Data from 30 prostate cancer patients obtained during two years of research were analyzed to determine the trueness and precision of the PCR fragment size determination. Additional experiments were performed to demonstrate the precision (repeatability, reproducibility) and robustness of PCR fragment concentration determination. Results The trueness and precision of the size determination was below 3% and 2% respectively. The repeatability of the concentration determination was below 15%. The difference in concentration determination increases when Multiplex-PCR/storage step is added between the two measurements of one sample. Conclusions The characteristics established in our study are in concordance with the manufacturer's specifications established for a ladder as a sample. However, the concentration determination may vary depending on chip preparation, sample storage and concentration. The 15% variation of concentration determination repeatability was shown to be partly proportional and can be suppressed by proper normalization.

The effectiveness of BD Vacutainer® Plus Urinalysis Preservative Tubes in preservation of urine for chemical strip analysis and particle counting

Abstract: Introduction The aim of this study was to evaluate the stability of urine collected in preservative tubes for chemistry strip analyses and particle counting to determine whether the transport of urine samples with all of their constituents is possible.

The effect of extremely high glucose concentrations on 21 routine chemistry and thyroid Abbott assays: interference study.

Abstract: Introduction Extremely high glucose concentrations have been shown to interfere with creatinine assays especially with Jaffe method in peritoneal dialysate. Because diabetes is the fastest growing chronic disease in the world, laboratories study with varying glucose concentrations. We investigated whether different levels of glucose spiked in serum interfere with 21 routine chemistry and thyroid assays at glucose concentrations between 17-51 mmol/L.

Abnormal gel flotation caused by contrast media during adrenal vein sampling

Abstract: INTRODUCTION During adrenal venous sampling (AVS) procedure, radiologists administer a contrast agent via the catheter to visualize the proper catheter position. MATERIALS AND METHODS A patient with primary aldosteronism diagnostic-hypothesis was admitted for AVS. A venogram was performed to confirm the catheter's position with 2mL of Iopamidol 300 mg/mL. Samples were collected with syringe connected to a hydrophilic coated catheter by low-pressure aspiration from each of the four collection sites: inferior vena cava in the suprarenal portion, inferior vena cava in the infrarenal portion, left adrenal vein, and right adrenal vein; then immediately transferred from syringe to tubes with gel separator. All tubes were centrifuged at 1200 x g for 10 minutes. RESULTS At the end of centrifugation process, primary blood tubes containing blood from inferior vena cava and left adrenal vein exhibited the standard gel separator barrier, while tubes from right adrenal vein showed abnormal flotation of gel separator. The radiologist confirmed the usage of 2.6 mL instead of 2.0 mL of Iopamidol 300 mg/mL. This iodinated contrast media, with 1.33 g/cm3 of density, was used close to the right adrenal vein due to some difficulty to access it. CONCLUSION The abnormal flotation of gel separator in samples taken from right adrenal vein can be explained by the usage of the iodinated contrast media. We suggest using plain-tubes (without gel separator) for AVS in order to avoid preanalytical nonconformities. Moreover, a blood volume equivalent to twice the catheter extension should be discarded to eliminate residual contrast media before collection of samples for laboratory assays.

Failure to review STAT clinical laboratory requests and its economical impact.

Abstract: BACKGROUND Failure to follow-up laboratory test results has been described as one of the major processes contributing to unsafe patient care. Currently, most of the laboratories do not know with certainty not only their rate of missed (or unreviewed) requests but the economical cost and impact that this issue implies. The aim of our study was to measure that rate and calculate the resulting costs. MATERIAL AND METHODS In January 2015, we checked in our Laboratory Information Management System (LIMS) for every emergency request from 1(st) July 2011 to 30(th) June 2014, if they had been reviewed by any allowed user or not. 319,064 requests were ordered during that period of time. Results were expressed as "ordered requests", "missed requests" and its percentage. Additionally, total cost of missed requests was calculated in euros (€). "Non-productive days" were theorised (as the days producing requests that were not reviewed) based on these results. RESULTS 7924 requests (2.5%) were never reviewed by clinicians. This represented a total cost of 203,039 € and 27 "non-productive" days in three years. Significant differences between inpatients, outpatients and emergency department as well as different emergencies units were found after application of statistical analysis. CONCLUSIONS In terms of resources, never reviewed or missed requests appear to be a not negligible problem for the clinical laboratory management. Electronic result delivery, with electronic endorsement to indicate follow-up of requests along with better systems of electronic requesting should be investigated as a way of improving patient outcomes and save unnecessary expenses.