Estimation of alert and change limits and its application in the plausibility control

In the clinical laboratory, one of the most objective ways to perform the final review of patients’ measured values is the use of computerized plausibility control (i.e., set of procedures used to decide whether a patient’s measured value is valid according to established clinical and biological criteria). This study is focused on the estimation of alert and change limits to be applied to detect doubtful patients’ measured values. These limits are useful to improve the final review of patients’ measured values since these limits are produced objectively and are selected according to the clinical laboratory needs, letting the clinical laboratory professional staff to save time and effort.     

Physiological reference values: a shared business? Report of the second European symposium on clinical laboratory and in vitro diagnostics industry

The Catalan Association of Clinical Laboratory Sciences, with the support of its corporative members, organized the second European symposium devoted to physiological reference values, in Barcelona. The objectives were: (i) to discuss ways to develop a common strategy among clinical laboratories and the in vitro diagnostic (IVD) industry for the generation of physiological reference values related to biological quantities of medical interest; and (ii) to establish consensus between both groups regarding the interpretation of the requirements related to physiological reference values contained in the European (EU) Directive 98/79-EC and in the EN-ISO 15189:2003 standard. The symposium was divided into four parts in which different aspects of the reference values were discussed: legal and normative aspects, alternatives to the production of own reference values, methodology, and diffusion and teaching. The main conclusions were the need to clarify the requirements described by the EU Directive 98/79-EC and EN-ISO 15189:2003 regarding reference values, and the need for cooperation between industry, clinical laboratories, and health authorities to achieve common reference intervals, including multicentric reference intervals.     

A quality systems approach for identifying and controlling sources of error with point of care testing devices

Historically, due to the size and nature of the instrumentation, highly skilled laboratory professionals performed clinical testing in centralized laboratories. Today’s clinicians demand realtime test data at the point of care. This has led to a new generation of compact, portable instruments permitting ”laboratory” testing to be performed at or near the patient’s bedside by nonlaboratory workers who are unfamiliar with testing practices. Poorly controlled testing processes leading to poor quality test results are an insidious problem facing point of care testing today. Manufacturers are addressing this issue through instrument design. Providers of clinical test results, regardless of location, working with manufacturers and regulators must create and manage complete test systems that eliminate or minimize sources of error. The National Committee for Clinical Laboratory Standards (NCCLS) in its EP18 guideline, ”Quality management for unit-use testing,” has developed a quality management system approach specifically for test devices used for point of care testing (POCT). Simply stated, EP18 utilizes a ”sources of error” matrix to identify and address potential errors that can impact the test result. The key is the quality systems approach where all stakeholders – professionals, manufacturers and regulators – collaboratively seek ways to manage errors and ensure quality. We illustrate the use of one quality systems approach, EP18, as a means to advance the quality of test results at point of care. Received: 26 June, 2002 Accepted: 17 July 2002 Presented at the European Conference on Quality in the Spotlight in Medical Laboratories, 7–9 October 2001, Antwerp, Belgium Abbreviations NCCLS National Committee for Clinical Laboratory Standards (formerly) · POCT point of care testing · QC quality control · HACCP hazard analysis critical control points · CLIA clinical laboratory improvement amendments (of 1988) Correspondence to S. S. Ehrmeyer     

Regulatory compliance vs. NEXUS quality for laboratory tests

In the U.S., all clinical laboratory testing is regulated by the Clinical Laboratory Improvement Amendments (CLIA) (). The CLIA link test quality and adherence to a body of testing regulations intended to ensure accurate, reliable, and timely patient test results. The goal of the CLIA legislation was to ensure a minimum, fundamental level of quality. In the context of “NEXUS,” quality must “go beyond getting the ‘right’ answer on the ‘right’ patient that can be interpreted against ‘right’ reference values. CLIA regulations with specific minimum, performance requirements, or safeguards, are designed to prevent testing errors. The US Institute of Medicine found that testing processes fail as a result of human error, lack of documentation, and lack of test management. In the latest (2004) interpretations of CLIA regulations, the minimum quality control requirement continues to be analyzing at least two external, liquid quality control materials per test per day. In 1995, we proposed that the responsibility for achieving quality test results shifts from the sole purview of the laboratory director to an “alliance” of laboratory professionals, manufacturers, and regulators. The EQC (equivalent quality control) concept as proposed is a positive step in achieving this alliance. With the obvious lack of scientific and statistical robustness, EQC falls far short of ensuring quality. Achieving the “NEXUS Vision” for quality laboratory testing will not come solely from laboratory professionals. The NEXUS is about how to ensure the full-quality assessment of the testing process – pre-analytical, analytical, and post-analytical.Presented at the 10th Conference Quality in the Spotlight, March 2005, Antwerp, Belgium.     

Setting a precedent in international accreditation

 The accreditation procedure that the Department of Laboratory Sciences, CHPPM-Europe underwent is described. The laboratory obtained ISO/IEC 25 accreditation through the American Association for Laboratory Accreditation (A2LA) and the Deutsches Akkreditierungssystem Prüfwesen (DAP) as well as EN 45001 from DAP following the A2LA and DAP joint inspection. The accreditation process and the importance of obtaining national and international accreditation are discussed. Received: 30 May 1997 · Accepted: 16 June 1997     

Use of prediction equations for reviewing measurement results in the clinical laboratory

In the clinical laboratory, one of the most objective ways to perform the final review of measurement results is the use of the so-called plausibility control (i.e., set of procedures used to decide if a measurement result is valid or not according to established clinical and biological criteria). The present study is focused on the estimation of several prediction equations derived from pairs of biological quantities having a pathophysiological relationship and statistically correlated to detect objectively doubtful results in the context of plausibility control. These prediction intervals, that may be used alone or combined with other procedures involved in the plausibility control, are a very useful tool for the improvement of the final review of the laboratory results.     

Is CLIA 2003 the quality alliance envisioned between manufacturers,laboratory professionals,and regulatory agencies?

The Clinical Laboratory Improvement Amendments of 1988 (CLIA88) had a groundbreaking effect on laboratory professionals, instrument and reagent manufacturers, and regulators in the United States, and by association, worldwide. CLIA88 defined new levels of responsibility for all three of these stakeholders in modern laboratory testing. As a result, we envisioned a CLIA-driven approach to regulations, which in effect, created a three-member quality alliance. In 2003, the long awaited CLIA updates to the quality control and quality assurance requirements were published. The revisions in CLIA 2003 will herald an era in which manufactures take responsibility for meeting new standards of quality (improved accuracy and precision or reduced total allowable error) in the clinical laboratory and, especially, at point of care where testing is performed by non-laboratorians. The European (Bureau International des Poids ed Mesures) efforts at traceability, the National Committee of Clinical Laboratory Standards efforts at estimating total allowable error, and the new CLIA 2003 quality systems approach for quality requirements return to the fundamental concepts of accuracy to assess the efficacy of clinical laboratory testing.Presented at the 8th Conference on Quality in the Spotlight, 17–18 March 2003, Antwerp, Belgium     

The ILAC Arrangement – Part I

As of August 2001, 38 laboratory accreditation bodies of the International Laboratory Accreditation Cooperation (ILAC) have signed the multi-lateral, mutual recognition arrangement (the ”ILAC Arrangement”) to promote the acceptance of accredited test and calibration data. This Arrangement provides significant technical underpinning to international trade. Until now, there has been no international mutual recognition agreement in laboratory accreditation, which has been a hindrance for some types of international trade. The key to the Arrangement is the developing global network of accredited testing and calibration laboratories that are assessed and recognised as being competent by ILAC Arrangement signatory accreditation bodies. The signatories have, in turn, been peer-reviewed and shown to meet ILAC’s criteria for competence. Now that the ILAC Arrangement is in place, governments can take advantage of it to further develop or enhance trade agreements. The ultimate aim is increased use and acceptance by industry, as well as government, of the results from accredited laboratories, including results from laboratories in other countries. In this way, the free-trade goal of ”a product tested once and accepted everywhere” can be realised.     

Characterization of Heterogeneous Catalysts by use of Test Reactions

The following report gives an overview on work done in the Catalysis Laboratory of the Department of Chemistry, National University of Singapore over the last 15 years (1989–2004). Much of this work can be described as “characterization of catalytically active surfaces through test reactions”. The methods, systems studied and the reactions that we evaluated will be described. The review will mostly concentrate on work from the authors’ laboratory, but other relevant work will also be cited.     

Aspects of auditing in clinical laboratories

Quality and patient safety are terms that both providers and recipients of healthcare are very familiar with. Accreditation is another term that is closely linked to quality and patient safety. Audit is a systematic, independent, and documented process for obtaining evidence and evaluating it objectively to determine the extent to which audit criteria are fulfilled. Accreditation and audit are integral components of the same process. Three different types of audit are well recognized—internal, external, and co-operative. Reading of relevant documents, observation of laboratory practices, and asking open-ended probing questions are important auditing techniques. For auditing to be successful, experienced, qualified, and well trained auditors are essential. Furthermore, the auditor should be open-minded, not prejudiced, a team player and effective communicator, both in writing and verbally. In many instances, the emphasis for seeking laboratory accreditation has shifted from building quality systems—to produce reliable results and ensure patient safety—to just passing the inspection. Recently, the emphasis for laboratory quality improvement has been placed on pre and post-analytical processes in preference to analytical quality. The analytical quality of laboratory results is still far from ideal and it may be detrimental if less emphasis is placed on this aspect of laboratory medicine. Auditing or on-site inspection as a regulatory tool does not work or present a realistic picture of laboratory quality. A continuous quality improvement approach will help laboratories to build quality into their systems. Presented at the Conference “Excellence in Laboratory Medicine”, November 2007, Al Ain, United Arab Emirates.     

Discussions about whether radioactive half life can be changed by mechanic motion

In this essay, some discussions and comments about the paper entitled “Can the decay rate of ³²P be changed by mechanic motion?” (Ding et al., Science in China Series B: Chemistry (Chinese version), 2008, 38(11):1035–1037) are given. It was strongly suggested that its experimental methods, data calculations and conclusion should be reconsidered. After the data were recalculated, the new results supported that the chiral mechanic motion could induce the changes of radioactive half life. Supported by the National Natural Science Foundation of China (Grant Nos. 20571085, and 20877099), Fund of the President of Chinese Academy of Sciences (Grant No. 0521021T04), 2005/2006 USA Li’s Foundation Merit Prize Fund, Fund of Graduate University of Chinese Academy of Sciences (Grant No. 065101HM03), and Fund of the Key Laboratory of Nuclear Analysis of the Institute of High Energy Physics of Chinese Academy of Sciences (Grant No. K129)     

The third edition of ISO Guide 34: what were the drivers for the revision and what is new?

After the International Laboratory Accreditation Cooperation (ILAC) had taken in 2004, the resolution to conduct accreditation of producers of reference materials according to ISO Guide 34 ‘General requirements for the competence of reference material producers’ in combination with ISO/IEC 17025 ‘General requirements for the competence of testing and calibration laboratories’, ISO/REMCO, the ISO Committee on Reference Materials, decided in 2005 to revise ISO Guide 34 to align it closer with ISO/IEC 17025 and to clarify certain issues for accreditors and producers seeking accreditation without adding new requirements. Moreover, the publication in 2007 of ISO/IEC Guide 99 ‘International vocabulary of metrology—Basic and general concepts and associated terms (VIM)’ triggered additional adaptations of the guide.     

Response to “About acceptance and rejection zones”

Desimoni and Brunetti raise some questions about the use of Eurachem/CITAC guide, because the Eurachem/CITAC guide does not discuss an ISO recommendation before performing a test, it should be decided whether it is to be a test for conformity or a test for non-conformity. In response, it is pointed out that although this recommendation is not discussed explicitly, it is of necessity covered by the decision rule that describes how the measurement uncertainty will be taken into consideration with regard to accepting or rejecting a product according to its specification and the result of a measurement. In addition, they propose the introduction of an ‘inconclusive’ zone. We do not think that this is necessary, since the Eurachem/CITAC guide takes the view that action on rejection should be covered by the ‘decision rule’ and this can make equivalent provision for confirmation or interpretation.     

Synthesis and anti-HIV-1 activity of S-dihydro(alkyloxy)benzyloxypyrimidine derivatives

Several 2-heteroaryl-, 2-heteroarylcarbonylmethyl-, 2-arylcarbonylmethyl, and 2-arylethyl derivatives of S-dihydro(alkyloxy)benzyloxypyrimidines have been synthesized and the anti-HIV activities of these compounds were tested in C8166 cell and against RT enzyme. It was found that some of these compounds showed good activity against HIV-1 (EC ₅₀ = 0.014–0.8 μM) with low toxicity (CC ₅₀ value of 222–564 μM) and high selectivity (SI value of 278–37743). The structure-activity relationships (SAR) of these compounds have also been discussed. First two authors contributed equally to this work Correspondence: Yan-Ping He, Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People’s Republic of China; Yong-Tang Zheng, Laboratory of Molecular Immunopharmacology, Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan 650223, People’s Republic of China.     

Use of the MALDI BioTyper system with MALDI–TOF mass spectrometry for rapid identification of microorganisms

In a clinical diagnosis microbiology laboratory, the current method of identifying bacterial isolates is based mainly on phenotypic characteristics, for example growth pattern on different media, colony morphology, Gram stain, and various biochemical reactions. These techniques collectively enable great accuracy in identifying most bacterial isolates, but are costly and time-consuming. In our clinical microbiology laboratory, we prospectively assessed the ability of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI–TOF MS) to identify bacterial strains that were routinely isolated from clinical samples. Bacterial colonies obtained from a total of 468 strains of 92 bacterial species isolated at the Department of Clinical Laboratory at Chiba University were directly placed on target MALDI plates followed by addition of CHCA matrix solution. The plates were then subjected to MALDI–TOF MS measurement and the microorganisms were identified by pattern matching with the libraries in the BioTyper 2.0 software. Identification success at the species and genus levels was 91.7% (429/468) and 97.0% (454/468), respectively. MALDI–TOF MS is a rapid, simple, and high-throughput proteomic technique for identification of a variety of bacterial species. Because colony-to-colony differences and effects of culture duration on the results are minimal, it can be implemented in a conventional laboratory setting. Although for some pathogens, preanalytical processes should be refined, and the current database should be improved to obtain more accurate results, the MALDI–TOF MS based method performs, in general, as well as conventional methods and is a promising technology in clinical laboratories.     

The American Association for Laboratory Accreditation

 The American Association for Laboratory Accreditation (A2LA) marks its 20th year of existence. Its major aim as a non-profit, public service organization is to promote laboratory quality and competence. In terms of the number of current accreditations, A2LA is the largest multidiscipline laboratory accreditation body in the United States and the fourth largest in the world. An overview of current activities and status is provided.     

Biological variation data are necessary prerequisites for objective autoverification of clinical laboratory data

The wealth of quantitative data on random biological variation has been used for setting quality specifications, assessing the utility of conventional reference values, and deciding of the significance of changes in serial laboratory results. Most analytes have marked individuality and this makes conventional population-based reference values of low utility. In consequence, reference limits are not ideal for autoverification strategies. Clinical decision limits may be better criteria for holding results for verification by laboratory professionals. Changes in serial results are significant only when the reference change value is exceeded. Such values can be generated by all laboratories and can be implemented, not only to flag reports, but also in delta checking and autoverification since these are objective rather than empirical. We have put these considerations into operation into our laboratory. Apart from special cases, our general approach is that results flagged as having changed 0.05<P<0.01, flagged as just outside the reference limits, or not flagged in any way, are autoverified and reported to the user without intervention. Only results outside pre-set clinical limits and those that have changed highly significantly P<0.01 are held for verification by clinical scientists and medical staff. This strategy allows autoverification of ca. 60% of reports. Received: 15 May 2002 Accepted: 17 July 2002 Presented at the European Conference on Quality in the Spotlight in Medical Laboratories, 7–9 October 2001, Antwerp, Belgium Correspondence to C. G. Fraser     

Quinquagenary of the Scientific Work of Prof. W. Zielenkiewicz

Prof. Wojciech Zielenkiewicz was born in Warsaw on 6 June 1933. He studied chemistry at the Warsaw University and graduated in 1955. His master thesis in the field of nuclear chemistry dealt with the enrichment of bromobenzene by the Szilard-Chalmers method. Since 1955 his professional career has mostly been related to the Institute of Physical Chemistry of the Polish Academy of Sciences (PAS) founded in the same year. Initially, Wojciech Zielenkiewicz worked under the supervision of Prof. Wojciech Świętosławski. This cooperation had a powerful influence on Zielenkiewicz both as a researcher and as a person. His strong interest in thermochemistry at that time resulted partly from his research interest and partly from his attraction to one of the students doing her diploma who later became his wife. Zielenkiewicz’s PhD thesis carried out under Świętosławski’s supervision concerned the thermochemistry of cement hydration. For the purposes of this work, Zielenkiewicz constructed his first calorimeter – a labyrinth flow calorimeter which was a modified version of the first such calorimeter constructed by Świętosławski and Malawski in 1935. The calorimeter was applied for the determination of the heat of cement hardening. After his PhD, Zielenkiewicz worked on several other calorimeters for the study of heat of cement hydration with the quasi-adiabatic method as well as on ‘conduction’ calorimeters for the examination of the first phase of cement hydration. This activity resulted in a monograph Calorimetry and Thermochemistry of Cement written in collaboration with T. Krupa and published in 1975. In the following years, his scientific interests were focused mostly on various aspects of the transfer of heat energy in time, i.e. thermokinetics. He constructed a number of calorimeters for this type of measurements and, together with his co-workers, elaborated new numerical methods of determination of thermokinetics. Those methods were assessed at international symposia on thermokinetics organised by Zielenkiewicz in cooperation with the French Association of Calorimetry and Thermal Analysis (AFCAT). In this period, he established regular cooperation with scientists from France, Spain, and the USA. Research on thermokinetics includes not only theoretical studies but also experimental works. Most of the experiments conducted at the Department of Calorimetry headed by Prof. Zielenkiewicz were connected with inclusion compounds, particularly Werner complexes as well as porfyrine derivatives. In the last twenty years, Zielenkiewicz conducted research in the scope of biomolecules. The study resulted in the determination of thermodynamic properties of over 60 derivatives of nucleic acid bases and the establishment of new correlations between enthalpic, volume, and structural properties of the compounds examined. His most recent interests concerned the study of enthalpic processes of protein salting. Zielenkiewicz’s long and intensive work in the field of calorimetry and thermokinetics has appeared in numerous books and publications presenting his research results. He is the author of 7 monographs, a number of chapters in a monograph and about 200 scientific publications. They include, among others, Analysis of Course of Heat Effect in n-n Calorimeters, Signal Processing of Calorimetric System, Dynamic Theory (later translated into Russian and published in Russia), Advances in Calorimetry and Thermochemistry, Theory of Calorimetry written together with E. Margas and published in 2002 by Kluwer and the most recent book, Calorimetry, published in 2005. Prof. Zielenkiewicz has also been active as a supervisor. He assisted and supported the realisation of 14 completed PhD theses of the employees at the Institute of Physical Chemistry and is supervising 3 more students of the Institute. Moreover, he has been involved in the realization of several more PhD theses both in Poland and abroad. For many years Prof. Zielenkiewicz combined his activity on research with research coordination. He managed the organizational units of the Polish Academy of Sciences as the Director General of the PAS and as a Deputy Scientific Secretary. For 6 years he was a Scientific Secretary of the Division of Mathematical, Physical and Chemical Sciences of PAS. In the years 1968–2003 he headed the Laboratory and Department of Calorimetry and he was a director of the Institute of Physical Chemistry for 19 years. His directorship in the Institute happened in a very difficult period for Poland, i.e. when the Marshall Law was introduced in 1981. As numerous employees of the Institute were involved in the illegal Solidarity movement at that time, the position of a director of such an institution was extremely uncomfortable and required great abilities in dealing with the communist authorities in such a way as to protect those employees. It must be said that Prof. Zielenkiewicz faced this challenge with success. Prof. Zielenkiewicz was also an initiator of the Polish conferences on calorimetry and thermal analysis. The first one was held over 30 years ago. These conferences created an opportunity for Polish researchers to exchange their opinions and learn about the world research trends. Numerous outstanding scientists were guests at these conferences. Many of them are members of the Polish Society of Calorimetry and Thermal Analysis. Prof. Zielenkiewicz has been awarded many state and foreign medals and distinctions, among others, Wojciech Świętosł;awski’s Medal and the Calvet Award given by the French Association of Calorimetry and Thermal Analysis (AFCAT) as well as the most prominent Polish state orders including the Order of Polonia Restituta (the Knight’s Cross) and the Order of Labour Banner. He is a corresponding member of the Polish Academy of Sciences and the Royal Academy of Sciences in Barcelona. Dr. Paweł Gierycz     

Guidance for accredited laboratories on the use of computers

 We review the draft international standard ISO/IEC 17025 and the EA guidelines; and present the existing National Physical Laboratory publication “Software in scientific instruments” and the new Measurement System Validation Best Practice guide. Received: 2 November 1999 / Accepted: 29 January 2000