Pre- versus Post-synaptic Forms of LTP in Two Branches of the Same Hippocampal Afferent.

There has been considerable controversy about pre- versus postsynaptic expression of memory-related long-term potentiation (LTP), with corresponding disputes about underlying mechanisms. We report here an instance in male mice, in which both types of potentiation are expressed but in separate branches of the same hippocampal afferent. Induction of LTP in the dentate gyrus (DG) branch of the lateral perforant path (LPP) reduces paired-pulse facilitation, is blocked by antagonism of cannabinoid receptor type 1, and is not affected by suppression of postsynaptic actin polymerization. These observations are consistent with presynaptic expression. The opposite pattern of results was obtained in the LPP branch that innervates the distal dendrites of CA3: LTP did not reduce paired-pulse facilitation, was unaffected by the cannabinoid receptor blocker, and required postsynaptic actin filament assembly. Differences in the two LPP termination sites were also noted for frequency facilitation of synaptic responses, an effect that was reproduced in a two-step simulation by small adjustments to vesicle release dynamics. These results indicate that different types of glutamatergic neurons impose different forms of filtering and synaptic plasticity on their afferents. They also suggest that inputs are routed to, and encoded by, different sites within the hippocampus depending upon the pattern of activity arriving over the parent axon.

Recommendation for the design of stability studies on clinical specimens.

OBJECTIVES: Knowledge of the stability of analytes in clinical specimens is a prerequisite for proper transport and preservation of samples to avoid laboratory errors. The new version of ISO 15189:2022 and the European directive 2017/746 increase the requirements on this topic for manufacturers and laboratories. Within the project to generate a stability database of European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Preanalytical Phase (WG-PRE), the need to standardise and improve the quality of published stability studies has been detected, being a manifest deficit the absence of international guidelines for the performance of stability studies on clinical specimens. METHODS: These recommendations have been developed and summarised by consensus of the WG-PRE and are intended primarily to improve the quality of sample stability claims included in information for users provided by assay supplier companies, according to the requirements of the new European regulations and standards for accreditation. RESULTS: This document provides general recommendations for the performance of stability studies, oriented to the estimation of instability equations in the usual working conditions, allowing flexible adaptation of the maximum permissible error specifications to obtain stability limits adapted to the intended use. CONCLUSIONS: We present this recommendation based on the opinions of the EFLM WG-PRE group for the standardisation and improvement of stability studies, with the intention to improve the quality of the studies and the transferability of their results to laboratories.

The CRESS checklist for reporting stability studies: on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase (WG-PRE).

To ensure that clinical laboratories produce results that are both accurate and of clinical utility it is essential that only samples of adequate quality are analysed. Although various studies and databases assessing the stability of analytes in different settings do exist, guidance on how to perform and report stability studies is lacking. This results in studies that often do not report essential information, thus compromising transferability of the data. The aim of this manuscript is to describe the Checklist for Reporting Stability Studies (CRESS) against which future studies should be reported to ensure standardisation of reporting and easy assessment of transferability of studies to other healthcare settings. The EFLM WG-PRE (European Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Preanalytical Phase) produced the CRESS checklist following a detailed literature review and extensive discussions resulting in consensus agreement. The checklist consists of 20 items covering all the aspects that should be considered when producing a report on a stability study including details of what should be included for each item and a rationale as to why. Adherence to the CRESS checklist will ensure that studies are reported in a transparent and replicable way. This will allow other laboratories to assess whether published data meet the stability criteria required in their own particular healthcare scenario. The EFLM WG-PRE encourage researchers and authors to use the CRESS checklist as a guide to planning stability studies and to produce standardised reporting of future stability studies.

Handling of hemolyzed serum samples in clinical chemistry laboratories: the Nordic hemolysis project.

Background Some clinical chemistry measurement methods are vulnerable to interference if hemolyzed serum samples are used. The aims of this study were: (1) to obtain updated information about how hemolysis affects clinical chemistry test results on different instrument platforms used in Nordic laboratories, and (2) to obtain data on how test results from hemolyzed samples are reported in Nordic laboratories. Methods Four identical samples containing different degrees of hemolysis were prepared and distributed to 145 laboratories in the Nordic countries. The laboratories were asked to measure the concentration of cell-free hemoglobin (Hb), together with 15 clinical chemistry analytes. In addition, the laboratories completed a questionnaire about how hemolyzed samples are handled and reported. Results Automated detection of hemolysis in all routine patient samples was used by 63% of laboratories, and 88% had written procedures on how to handle hemolyzed samples. The different instrument platforms measured comparable mean Hb concentrations in the four samples. For most analytes, hemolysis caused a homogenous degree of interference regardless of the instrument platform used, except for alkaline phosphatase (ALP), bilirubin (total) and creatine kinase (CK). The recommended cut-off points for rejection of a result varied substantially between the manufacturers. The laboratories differed in how they reported test results, even when they used the same type of instrument. Conclusions Most of the analytes were homogeneously affected by hemolysis, regardless of the instrument used. There is large variation, however, between the laboratories on how they report test results from hemolyzed samples, even when they use the same type of instrument.

European survey on preanalytical sample handling - Part 1: How do European laboratories monitor the preanalytical phase? On behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase (WG-PRE).

INTRODUCTION: Compared to other activities of the testing process, the preanalytical phase is plagued by a lower degree of standardization, which makes it more vulnerable to errors. With the aim of providing guidelines and recommendations, the EFLM WG-PRE issued a survey across European medical laboratories, to gather information on local preanalytical practices. This is part one of two coherent articles, which covers all practices on monitoring preanalytical quality except haemolysis, icterus and lipemia (HIL). MATERIALS AND METHODS: An online survey, containing 39 questions dealing with a broad spectrum of preanalytical issues, was disseminated to EFLM member countries. The survey included questions on willingness of laboratories to engage in preanalytical issues. RESULTS: Overall, 1405 valid responses were received from 37 countries. 1265 (94%) responders declared to monitor preanalytical errors. Assessment, documentation and further use of this information varied widely among respondents and partially among countries. Many responders were interested in a preanalytical online platform, holding information on various aspects of the preanalytical phase (N = 1177; 87%), in a guideline for measurement and evaluation of preanalytical variables (N = 1235; 92%), and in preanalytical e-learning programs or webinars (N = 1125; 84%). Fewer responders were interested in, or already participating in, preanalytical EQA programs (N = 951; 71%). CONCLUSION: Although substantial heterogeneity was found across European laboratories on preanalytical phase monitoring, the interest in preanalytical issues was high. A large majority of participants indicated an interest in new guidelines regarding preanalytical variables and learning activities. This important data will be used by the WG-PRE for providing recommendations on the most critical issues.

European survey on preanalytical sample handling - Part 2: Practices of European laboratories on monitoring and processing haemolytic, icteric and lipemic samples. On behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase (WG-PRE).

INTRODUCTION: No guideline currently exists on how to detect or document haemolysis, icterus or lipemia (HIL) in blood samples, nor on subsequent use of this information. The EFLM WG-PRE has performed a survey for assessing current practices of European laboratories in HIL monitoring. This second part of two coherent articles is focused on HIL. MATERIALS AND METHODS: An online survey, containing 39 questions on preanalytical issues, was disseminated among EFLM member countries. Seventeen questions exclusively focused on assessment, management and follow-up actions of HIL in routine blood samples. RESULTS: Overall, 1405 valid responses from 37 countries were received. A total of 1160 (86%) of all responders stating to analyse blood samples - monitored HIL. HIL was mostly checked in clinical chemistry samples and less frequently in those received for coagulation, therapeutic drug monitoring and serology/infectious disease testing. HIL detection by automatic HIL indices or visual inspection, along with haemolysis cut-offs definition, varied widely among responders. A quarter of responders performing automated HIL checks used internal quality controls. In haemolytic/icteric/lipemic samples, most responders (70%) only rejected HIL-sensitive parameters, whilst about 20% released all test results with general comments. Other responders did not analysed but rejected the entire sample, while some released all tests, without comments. Overall, 26% responders who monitored HIL were using this information for monitoring phlebotomy or sample transport quality. CONCLUSION: Strategies for monitoring and treating haemolytic, icteric or lipemic samples are quite heterogeneous in Europe. The WG-PRE will use these insights for developing and providing recommendations aimed at harmonizing strategies across Europe.

Pre-analytical practices for routine coagulation tests in European laboratories. A collaborative study from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM).

Background Correct handling and storage of blood samples for coagulation tests are important to assure correct diagnosis and monitoring. The aim of this study was to assess the pre-analytical practices for routine coagulation testing in European laboratories. Methods In 2013-2014, European laboratories were invited to fill in a questionnaire addressing pre-analytical requirements regarding tube fill volume, citrate concentration, sample stability, centrifugation and storage conditions for routine coagulation testing (activated partial thromboplastin time [APTT], prothrombin time in seconds [PT-sec] and as international normalised ratio [PT-INR] and fibrinogen). Results A total of 662 laboratories from 28 different countries responded. The recommended 3.2% (105-109 mmol/L) citrate tubes are used by 74% of the laboratories. Tube fill volumes ≥90% were required by 73%-76% of the laboratories, depending upon the coagulation test and tube size. The variation in centrifugation force and duration was large (median 2500 g [10- and 90-percentiles 1500 and 4000] and 10 min [5 and 15], respectively). Large variations were also seen in the accepted storage time for different tests and sample materials, for example, for citrated blood at room temperature the accepted storage time ranged from 0.5-72 h and 0.5-189 h for PT-INR and fibrinogen, respectively. If the storage time or the tube fill requirements are not fulfilled, 72% and 84% of the respondents, respectively, would reject the samples. Conclusions There was a large variation in pre-analytical practices for routine coagulation testing in European laboratories, especially for centrifugation conditions and storage time requirements.

Status on fasting definition for blood sampling in the Nordic countries - time for a harmonized definition.

The preanalytical phase contains a vast number of practices whose variation may influence the results of laboratory testing and should, therefore, be standardized. The Working Group on Preanalytical Phase of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM WG-PA) has suggested a standardization of venous blood specimen collection (VBSC) requirements for fasting samples including 12 h fasting time and water ad lib in the morning prior to specimen collection. The Nordic Scientific Preanalytical Working Group investigated the fasting definitions used in the Nordic countries. The Internet was assessed for stated fasting definitions of official organizations, larger laboratories, or laboratory groups. Fasting instructions for VBSC generally demanded patients to abstain from alcohol a day prior to, and to abstain from coffee, tea, smoking, and snuff intake in the morning of VBSC. Norway had a national fasting definition. Required fasting times varied from 8 to 14 h. The amount of water allowed in the morning of VBSC varied from ad lib to half a glass of water. The list of analytes, where fasting was required, held 9-15 analytes except for Finland with 65 analytes. Implementation of the EFLM WG-PRE standardization of VBSC requirements for fasting samples would decrease preanalytical variability and be beneficial for medical decisions and patient data comparison. We suggest the laboratories in the Nordic countries to implement the suggested fasting requirements, which are in line with those used when fasting reference intervals were established in the Nordic reference interval project.

Joint EFLM-COLABIOCLI Recommendation for venous blood sampling

This document provides a joint recommendation for venous blood sampling of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE) and Latin American Working Group for Preanalytical Phase (WG-PRE-LATAM) of the Latin America Confederation of Clinical Biochemistry (COLABIOCLI). It offers guidance on the requirements for ensuring that blood collection is a safe and patient-centered procedure and provides practical guidance on how to successfully overcome potential barriers and obstacles to its widespread implementation. The target audience for this recommendation are healthcare staff members directly involved in blood collection. This recommendation applies to the use of a closed blood collection system and does not provide guidance for the blood collection with an open needle and syringe and catheter collections. Moreover, this document neither addresses patient consent, test ordering, sample handling and transport nor collection from children and unconscious patients. The recommended procedure is based on the best available evidence. Each step was graded using a system that scores the quality of the evidence and the strength of the recommendation. The process of grading was done at several face-to-face meetings involving the same mixture of stakeholders stated previously. The main parts of this recommendation are: 1) Pre-sampling procedures, 2) Sampling procedure, 3) Post-sampling procedures and 4) Implementation. A first draft of the recommendation was circulated to EFLM members for public consultation. WG-PRE-LATAM was also invited to comment the document. A revised version has been sent for voting on to all EFLM and COLABIOCLI members and has been officially endorsed by 33/40 EFLM and 21/21 COLABIOCLI members. We encourage professionals throughout Europe and Latin America to adopt and implement this recommendation to improve the quality of blood collection practices and increase patient and workers safety.

Endogenous neurosteroids influence synaptic GABAA receptors during postnatal development.

GABA plays a key role in both embryonic and neonatal brain development. For example, during early neonatal nervous system maturation, synaptic transmission, mediated by GABAA receptors (GABAA Rs), undergoes a temporally specific form of synaptic plasticity to accommodate the changing requirements of maturing neural networks. Specifically, the duration of miniature inhibitory postsynaptic currents (mIPSCs), resulting from vesicular GABA activating synaptic GABAA Rs, is reduced, permitting neurones to appropriately influence the window for postsynaptic excitation. Conventionally, programmed expression changes to the subtype of synaptic GABAA R are primarily implicated in this plasticity. However, it is now evident that, in developing thalamic and cortical principal- and inter-neurones, an endogenous neurosteroid tone (eg, allopregnanolone) enhances synaptic GABAA R function. Furthermore, a cessation of steroidogenesis, as a result of a lack of substrate, or a co-factor, appears to be primarily responsible for early neonatal changes to GABAergic synaptic transmission, followed by further refinement, which results from subsequent alterations of the GABAA R subtype. The timing of this cessation of neurosteroid influence is neurone-specific, occurring by postnatal day (P)10 in the thalamus but approximately 1 week later in the cortex. Neurosteroid levels are not static and change dynamically in a variety of physiological and pathophysiological scenarios. Given that GABA plays an important role in brain development, abnormal perturbations of neonatal GABAA R-active neurosteroids may have not only a considerable immediate, but also a longer-term impact upon neural network activity. Here, we review recent evidence indicating that changes in neurosteroidogenesis substantially influence neonatal GABAergic synaptic transmission. We discuss the physiological relevance of these findings and how the interference of neurosteroid-GABAA R interaction early in life may contribute to psychiatric conditions later in life.

Life history and ecology of the elusive European short-snouted seahorse Hippocampus hippocampus.

To improve the understanding of the life history and ecology of one of Europe's most elusive fishes, the short-snouted seahorse Hippocampus hippocampus, data from wild populations in a shallow coastal lagoon in southern Portugal were analysed. The data were collected from 17 tagged seahorses on a focal-study grid as well as from >350 seahorses encountered during underwater visual surveys and a fishery-independent study using beach seines. These populations of settled juveniles and adults had a mean population density of 0·009 m-2 . During the study period (2000-2004), reproduction peaked in July and August. Juveniles recruited to the lagoon at c. 66 mm standard length (LS ) and 0·5 years of age and established small home ranges (0·8 to 18·2 m2 ). First reproduction was estimated at 100 mm and 1 year of age. Based on a fitted von Bertalanffy model, H. hippocampus grew quickly (growth coefficient K = 0·93) to a maximum theoretical size L∞ = 150 mm and have a maximum lifespan of c. 3·2 years. Courtship behaviours were consistent with the maintenance of pair bonds and males brooded multiple batches of young per year. Estimated annual reproductive output averaged 871 young (±632). Together these analyses provide the first life-history parameters for this species and indicate that H. hippocampus bears characteristics of opportunist and intermediate strategists. Such populations are predicted to exhibit large fluctuations in abundance, making them vulnerable to extended periods of poor recruitment.

Stress and Seizures: Space, Time and Hippocampal Circuits.

Stress is a major trigger of seizures in people with epilepsy. Exposure to stress results in the release of several stress mediators throughout the brain, including the hippocampus, a region sensitive to stress and prone to seizures. Stress mediators interact with their respective receptors to produce distinct effects on the excitability of hippocampal neurons and networks. Crucially, these stress mediators and their actions exhibit unique spatiotemporal profiles, generating a complex combinatorial output with time- and space-dependent effects on hippocampal network excitability and seizure generation.

The Endogenous Stress Hormone CRH Modulates Excitatory Transmission and Network Physiology in Hippocampus.

Memory is strongly influenced by stress but underlying mechanisms are unknown. Here, we used electrophysiology, neuroanatomy, and network simulations to probe the role of the endogenous, stress-related neuropeptide corticotropin-releasing hormone (CRH) in modulating hippocampal function. We focused on neuronal excitability and the incidence of sharp waves (SPWs), a form of intrinsic network activity associated with memory consolidation. Specifically, we blocked endogenous CRH using 2 chemically distinct antagonists of the principal hippocampal CRH receptor, CRHR1. The antagonists caused a modest reduction of spontaneous excitatory transmission onto CA3 pyramidal cells, mediated, in part by effects on IAHP. This was accompanied by a decrease in the incidence but not amplitude of SPWs, indicating that the synaptic actions of CRH are sufficient to alter the output of a complex hippocampal network. A biophysical model of CA3 described how local actions of CRH produce macroscopic consequences including the observed changes in SPWs. Collectively, the results provide a first demonstration of the manner in which subtle synaptic effects of an endogenously released neuropeptide influence hippocampal network level operations and, in the case of CRH, may contribute to the effects of acute stress on memory.

Analytical Bias Exceeding Desirable Quality Goal in 4 out of 5 Common Immunoassays: Results of a Native Single Serum Sample External Quality Assessment Program for Cobalamin, Folate, Ferritin, Thyroid-Stimulating Hormone, and Free T4 Analyses.

BACKGROUND: We undertook this study to evaluate method differences for 5 components analyzed by immunoassays, to explore whether the use of method-dependent reference intervals may compensate for method differences, and to investigate commutability of external quality assessment (EQA) materials. METHODS: Twenty fresh native single serum samples, a fresh native serum pool, Nordic Federation of Clinical Chemistry Reference Serum X (serum X) (serum pool), and 2 EQA materials were sent to 38 laboratories for measurement of cobalamin, folate, ferritin, free T4, and thyroid-stimulating hormone (TSH) by 5 different measurement procedures [Roche Cobas (n = 15), Roche Modular (n = 4), Abbott Architect (n = 8), Beckman Coulter Unicel (n = 2), and Siemens ADVIA Centaur (n = 9)]. The target value for each component was calculated based on the mean of method means or measured by a reference measurement procedure (free T4). Quality specifications were based on biological variation. Local reference intervals were reported from all laboratories. RESULTS: Method differences that exceeded acceptable bias were found for all components except folate. Free T4 differences from the uncommonly used reference measurement procedure were large. Reference intervals differed between measurement procedures but also within 1 measurement procedure. The serum X material was commutable for all components and measurement procedures, whereas the EQA materials were noncommutable in 13 of 50 occasions (5 components, 5 methods, 2 EQA materials). CONCLUSIONS: The bias between the measurement procedures was unacceptably large in 4/5 tested components. Traceability to reference materials as claimed by the manufacturers did not lead to acceptable harmonization. Adjustment of reference intervals in accordance with method differences and use of commutable EQA samples are not implemented commonly.

Patient identification and tube labelling - a call for harmonisation.

Venous blood sampling (phlebotomy) is the most common invasive procedure performed in patient care. Guidelines on the correct practice of phlebotomy are available, including the H3-A6 guideline issued by the Clinical Laboratory Standards Institute (CLSI). As the quality of practices and procedures related to venous blood sample collection in European countries was unknown, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase conducted an observational study in 12 European countries. The study demonstrated that the level of compliance of phlebotomy procedures with the CLSI H3-A6 guideline was unacceptably low, and that patient identification and tube labelling are amongst the most critical steps in need of immediate attention and improvement. The process of patient identification and tube labelling is an essential safety barrier to prevent patient identity mix-up. Therefore, the EFLM Working Group aims to encourage and support worldwide harmonisation of patient identification and tube labelling procedures in order to reduce the risk of preanalytical errors and improve patient safety. With this Position paper we wish to raise awareness and provide recommendations for proper patient and sample identification procedures.

Preanalytical quality improvement. In pursuit of harmony, on behalf of European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working group for Preanalytical Phase (WG-PRE).

Laboratory diagnostics develop through different phases that span from test ordering (pre-preanalytical phase), collection of diagnostic specimens (preanalytical phase), sample analysis (analytical phase), results reporting (postanalytical phase) and interpretation (post-postanalytical phase). Although laboratory medicine seems less vulnerable than other clinical and diagnostic areas, the chance of errors is not negligible and may adversely impact on quality of testing and patient safety. This article, which continues a biennial tradition of collective papers on preanalytical quality improvement, is aimed to provide further contributions for pursuing quality and harmony in the preanalytical phase, and is a synopsis of lectures of the third European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)-Becton Dickinson (BD) European Conference on Preanalytical Phase meeting entitled 'Preanalytical quality improvement. In pursuit of harmony' (Porto, 20-21 March 2015). The leading topics that will be discussed include unnecessary laboratory testing, management of test request, implementation of the European Union (EU) Directive on needlestick injury prevention, harmonization of fasting requirements for blood sampling, influence of physical activity and medical contrast media on in vitro diagnostic testing, recent evidence about the possible lack of necessity of the order of draw, the best practice for monitoring conditions of time and temperature during sample transportation, along with description of problems emerging from inappropriate sample centrifugation. In the final part, the article includes recent updates about preanalytical quality indicators, the feasibility of an External Quality Assessment Scheme (EQAS) for the preanalytical phase, the results of the 2nd EFLM WG-PRE survey, as well as specific notions about the evidence-based quality management of the preanalytical phase.

Compliance of blood sampling procedures with the CLSI H3-A6 guidelines: An observational study by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PRE).

BACKGROUND: An observational study was conducted in 12 European countries by the European Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Preanalytical Phase (EFLM WG-PRE) to assess the level of compliance with the CLSI H3-A6 guidelines. METHODS: A structured checklist including 29 items was created to assess the compliance of European phlebotomy procedures with the CLSI H3-A6 guideline. A risk occurrence chart of individual phlebotomy steps was created from the observed error frequency and severity of harm of each guideline key issue. The severity of errors occurring during phlebotomy was graded using the risk occurrence chart. RESULTS: Twelve European countries participated with a median of 33 (18-36) audits per country, and a total of 336 audits. The median error rate for the total phlebotomy procedure was 26.9 % (10.6-43.8), indicating a low overall compliance with the recommended CLSI guideline. Patient identification and test tube labelling were identified as the key guideline issues with the highest combination of probability and potential risk of harm. Administrative staff did not adhere to patient identification procedures during phlebotomy, whereas physicians did not adhere to test tube labelling policy. CONCLUSIONS: The level of compliance of phlebotomy procedures with the CLSI H3-A6 guidelines in 12 European countries was found to be unacceptably low. The most critical steps in need of immediate attention in the investigated countries are patient identification and tube labelling.

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

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.

Self-monitoring of blood glucose with a focus on analytical quality: an overview.

Self-monitoring of blood glucose (SMBG) has been available for patients with diabetes for more than 30 years. Today, SMBG is an important component in diabetes management, helping patients achieve and maintain normal blood glucose concentrations. Implementation of SMBG as an effective glycaemic control tool requires that instruments have acceptable analytical quality, that the patients are educated in using them, and that actions are taken upon the results. This paper gives an overview of SMBG, including the history, clinical utility, principles of measurement and several aspects of analytical quality of SMBG. The latter comprises a standardised evaluation of SMBG performance, quality specifications as well as different approaches to monitor the quality of SMBG performance.