National External Quality Assurance Scheme Research Articles

Predicting flow cytometry crossmatch results from single-antigen bead testing.

The aim of this study was to devise an algorithm that would predict flow cytometry crossmatch (FCXM) results using single-antigen bead (SAB) mean fluorescent intensity (MFI) levels using samples received through the National External Quality Assurance Scheme (NEQAS) 2B external proficiency testing scheme between 2019 and 2023. A total of 159 serum samples were retrospectively screened using LABScreen Single Antigen Class I and II (SAB), and 40 peripheral blood samples were human leucocyte antigen (HLA) typed with LABType SSO. Donor-specific antibodies were identified for each cell-serum combination tested, and cumulative MFI values were calculated for each test before correlating the screening result with the consensus crossmatch results for this scheme. HLA Class I MFIs were combined to predict the T cell crossmatch. For the B cell crossmatch prediction, two options were considered: (i) HLA Class II MFI values alone and (ii) HLA Class I+Class II MFIs. Receiver operating characteristic analysis was carried out to identify the combined MFI threshold that predicted NEQAS consensus results with the greatest sensitivity and specificity. HLA Class I combined MFI >5000 predicted T cell crossmatch results with 96% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 92% negative predictive value (NPV). For B cell results, HLA Class I+Class II combined MFIs >11,000 gave the best model, showing 97% sensitivity, 82% specificity, 96% PPV and 85% NPV. However, for samples with only HLA Class II sensitization, combined MFIs >13,000 improved the B cell crossmatch predictions: 92% sensitivity, 95% specificity, 96% PPV and 91% NPV. Using this model, combined MFI can be used to predict the immunological risk posed by donor-specific antibodies when it is not possible to carry out an FCXM.

Editorial introductions

Editorial introductions

The landscape of diagnostic mycobacteriology in Germany-challenges of decentralised care.

OBJECTIVE: To perform a nationwide inventory of diagnostic mycobacteriology services in Germany.METHOD: A survey was conducted among participants of the national mycobacteriology external quality assurance scheme asking for smear microscopy techniques, molecular assays, culture systems and drug susceptibility testing (DST) capacities for Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM), and numbers of processed/culture-positive samples, and DSTs performed in 2016.RESULTS: We found that 170/238 laboratories (71.4%) provided data. Numbers of samples processed for culture varied between 35 and 40 000 (median 1856, interquartile range [IQR] 761-3500). Specimen numbers culture-positive for MTBC or NTM ranged from 0 to 1895 (median 46, IQR 17-116), and from 0 to 833 (median 30, IQR 13-71), respectively. Numbers of performed first-line susceptibility tests varied between 3 and 1400 (median 36, IQR 28-78). Eight laboratories performed DST for NTM. Also, 26.9% of all laboratories did not offer rapid genotypic DST (gDST) from primary samples.CONCLUSION: The landscape of diagnostic mycobacteriology in Germany is highly heterogenic with considerable variations in sample numbers and testing methodologies. Shortcomings exist with respect to fluorochrome staining of primary samples, rapid gDST of MTBC, and DST of NTM. National guidelines need to be adapted accordingly.

Personalized and Regeneration Medicine require a Coagulum-OMICs Model

Background: In 2017, a program on patient blood management was posted to the National External Quality Assurance Scheme conference for hemostasis and thrombosis [1]. This subsequent coagulum-OMIC framework is a standard for predictive value within personalized and regeneration medicine. An OMIC model is a foresight by the author of this program to achieve OMIC flow [View Fig. 1.]. This model sustains the success of Coagulum-OMICS when supported with the ISO 9000 series. [2] [3] [4]. Study: ISO 9001 and 9004 are powerful tools to identify and define good practice in an OMIC model. ISO 9001 is a process based standard and an ideal standard for OMIC interfaces. The greater challenge in haemostasis and thrombosis is the end to end process involves several parts of healthcare under different clinical management or vendor arrangements. The flexibility of ISO 9004 makes it an ideal tool to access Coagulum-OMICs and sustain the success of personalised and regeneration medicine. Program Development: A strategy for Research, Family, Organ and Acute Coagulum-OMICs commences biphasic policy objectives for genomics as a primary care with viscoelastic science, coagulum and platelet proteomics [Fig. 2]. Model OMIC development, resources, performance review and innovation, become learned. OMIC teams self-assess the Coagulum-OMICs to identify conformity with the model. Regional committees are supported by a joint working group on quality assurance to manage or improve OMICs Conclusion: A model for blood coagulum-OMICs is a benchmark to sustain excellence in the future of biological systems. The agility of Coagulum-OMICS to transverse primary and secondary care with genomic [pharma] pre-exams and viscoelastic or proteomic exams makes it a perfect learning initiative, selfassessment tool and governance program. The caveat is a need for expertise to sustain the success of coagulum-OMICs, in situ, with personalised and regeneration medicine

Falsely low immunoglobulin (Ig)G4 in routine analysis: how not to miss IgG4 disease.

Immunoglobulin (Ig)G4 disease can have apparently 'normal' levels of IgG4 due to antigen excess conditions. IgG4 measurement therefore appears falsely low. UK National External Quality Assurance Scheme (UK NEQAS) data and other reports have suggested that this problem occurred despite pre-existing antigen excess detection steps. To determine the clinical relevance of the problem, we examined the prevalence and characteristics of prozoning in our laboratory and patient cohorts. We establish that the prevalence of raised IgG4 in routine IgG4 analysis is low (< 1%) using one of the two routine methods in use in the United Kingdom. We show that subsequent assay modification appears to have reduced the likelihood of misleading readings. However, the original version of the assay prozoned to low levels (below 0·64 g/l) in 41% of high IgG4 samples in our patients. This may explain the previous reports of low sensitivity of raised IgG4 for IgG4RD, and predictive values should be re-evaluated in this disease using modified prozone-resistant protocols. All laboratories providing IgG4 measurements should verify that their assays are fit for the clinical quality requirement of detection raised IgG4 levels and must verify the upper limit of their reference ranges and freedom from prozoning.

A novel high-throughput method for supported liquid extraction of retinol and alpha-tocopherol from human serum and simultaneous quantitation by liquid chromatography tandem mass spectrometry.

Measurement of vitamin A (retinol) and E (alpha-tocopherol) in UK clinical laboratories is currently performed exclusively by high-performance liquid chromatography with ultraviolet detection. We investigated whether retinol and alpha-tocopherol could be measured simultaneously by liquid chromatography tandem mass spectrometry. Serum samples (100 μL) were extracted using Isolute + Supported Liquid Extraction plates. Chromatography was performed on a Phenomenex Kinetex Biphenyl 2.6 μm, 50 × 2.1 mm column, and liquid chromatography tandem mass spectrometry on a Waters Acquity TQD. Injection-to-injection time was 4.3 min. The assay was validated according to published guidelines. Patient samples were used to compare liquid chromatography tandem mass spectrometry and high-performance liquid chromatography with ultraviolet detection methods. For retinol and alpha-tocopherol, respectively, the assay was linear up to 6.0 and 80.0 μmol/L, and lower limit of quantification was 0.07 and 0.26 μmol/L. Intra and interassay imprecision were within desirable analytical specifications. Analysis of quality control material aligned to NIST SRM 968e, and relative spiked recovery from human serum, both yielded results within 15% of target values. Method comparison with high-performance liquid chromatography with ultraviolet detection methodology demonstrated a negative bias for retinol and alpha-tocopherol by the liquid chromatography tandem mass spectrometry method. Analysis of United Kingdom National External Quality Assurance Scheme samples yielded mean bias from the target value of +3.0% for retinol and -11.2% for alpha-tocopherol. We have developed a novel, high-throughput method for extraction of retinol and alpha-tocopherol from human serum followed by simultaneous quantitation by liquid chromatography tandem mass spectrometry. The method offers a rapid, sensitive, specific and cost-effective alternative to high-performance liquid chromatography with ultraviolet detection methodology, and is suitable for routine clinical monitoring of patients predisposed to fat-soluble vitamin malabsorption.

KRAS mutation testing of tumours in adults with metastatic colorectal cancer: a systematic review and cost-effectiveness analysis.

Bowel cancer is the third most common cancer in the UK. Most bowel cancers are initially treated with surgery, but around 17% spread to the liver. When this happens, sometimes the liver tumour can be treated surgically, or chemotherapy may be used to shrink the tumour to make surgery possible. Kirsten rat sarcoma viral oncogene (KRAS) mutations make some tumours less responsive to treatment with biological therapies such as cetuximab. There are a variety of tests available to detect these mutations. These vary in the specific mutations that they detect, the amount of mutation they detect, the amount of tumour cells needed, the time to give a result, the error rate and cost. To compare the performance and cost-effectiveness of KRAS mutation tests in differentiating adults with metastatic colorectal cancer whose metastases are confined to the liver and are unresectable and who may benefit from first-line treatment with cetuximab in combination with standard chemotherapy from those who should receive standard chemotherapy alone. Thirteen databases, including MEDLINE and EMBASE, research registers and conference proceedings were searched to January 2013. Additional data were obtained from an online survey of laboratories participating in the UK National External Quality Assurance Scheme pilot for KRAS mutation testing. A systematic review of the evidence was carried out using standard methods. Randomised controlled trials were assessed for quality using the Cochrane risk of bias tool. Diagnostic accuracy studies were assessed using the QUADAS-2 tool. There were insufficient data for meta-analysis. For accuracy studies we calculated sensitivity and specificity together with 95% confidence intervals (CIs). Survival data were summarised as hazard ratios and tumour response data were summarised as relative risks, with 95% CIs. The health economic analysis considered the long-term costs and quality-adjusted life-years associated with different tests followed by treatment with standard chemotherapy or cetuximab plus standard chemotherapy. The analysis took a 'no comparator' approach, which implies that the cost-effectiveness of each strategy will be presented only compared with the next most cost-effective strategy. The de novo model consisted of a decision tree and Markov model. The online survey indicated no differences between tests in batch size, turnaround time, number of failed samples or cost. The literature searches identified 7903 references, of which seven publications of five studies were included in the review. Two studies provided data on the accuracy of KRAS mutation testing for predicting response to treatment in patients treated with cetuximab plus standard chemotherapy. Four RCTs provided data on the clinical effectiveness of cetuximab plus standard chemotherapy compared with that of standard chemotherapy in patients with KRAS wild-type tumours. There were no clear differences in the treatment effects reported by different studies, regardless of which KRAS mutation test was used to select patients. In the 'linked evidence' analysis the Therascreen KRAS RGQ PCR Kit (QIAGEN) was more expensive but also more effective than pyrosequencing or direct sequencing, with an incremental cost-effectiveness ratio of £17,019 per quality-adjusted life-year gained. In the 'assumption of equal prognostic value' analysis the total costs associated with the various testing strategies were similar. The results assume that the differences in outcomes between the trials were solely the result of the different mutation tests used to distinguish between patients; this assumption ignores other factors that might explain this variation. There was no strong evidence that any one KRAS mutation test was more effective or cost-effective than any other test. PROSPERO CRD42013003663. The National Institute for Health Research Health Technology Assessment programme.

High-titre circulating tissue transglutaminase-2 antibodies predict small bowel villous atrophy, but decision cut-off limits must be locally validated

Numerous studies suggest that high levels of circulating immunoglobulin (Ig)A tissue transglutaminase (TTG2) antibodies predict coeliac disease with high specificity. Accordingly, it has been suggested that duodenal biopsy may not be required routinely for diagnostic confirmation where quantitative serology identifies the presence of high antibody titres. However, defining a cut-off TTG2 threshold is problematic, as the multiple available assay methods are not harmonized and most studies have been focused on the paediatric population. Recent paediatric guidelines proposed a TTG2 antibody diagnostic cut-off at 10 × the upper limit of normal (ULN) for the method; however, concerns remain about errors of generalization, between both methods and laboratories. In this study, we used retrospective laboratory data to investigate the relationship between TTG2 antibody levels and Marsh 3 histology in the seropositive population of adults and children at a single centre. Among 202 seropositive patients with corresponding biopsies, it was possible to define a TTG2 antibody cut-off with 100% specificity for Marsh 3 histology, at just over 10 × ULN for the method. However, UK National External Quality Assurance Scheme returns during the study period showed a wide dispersion of results and poor consensus, both between methods and between laboratories using the same method. Our results support the view that high-titre TTG2 antibody levels have strong predictive value for villous atrophy in adults and children, but suggest that decision cut-offs to guide biopsy requirement will require local validation. TTG2 antibody assay harmonization is a priority, in order to meet the evolving requirements of laboratory users in this field.

The Effect of 'On-Line' POCT on Patient waiting times in an Accident and Emergency Department.

This POCT (point of care testing) team was constructed at the start of 2012 to implement the POCT project aiming to define and test the hypothesis that interfacing POCT devices to a clinical electronic order communications system reduces patient waiting times in an NHS Accident and Emergency Department (A&E). The devices selected for evaluation initially comprised the Sysmex XS 1000i haematology analyser and the Abbott i-Stat chemistry analyser.The POCT devices were interfaced to a server (Midlynx) which in turn was connected via the hospital internal network, to the ICE system (Integrated Clinical Environment). Test orders entered on the ICE system produced a bar code label read by the individual POCT devices. Once required tests were assayed, the results were transmitted back to the ICE system, where they could be viewed by users across the hospital site. The quality of POCT analytical performance was assessed by running quality control checks as recommended by the manufacturers and by exchanging samples daily with the clinical laboratory. The I-Stat (a Chemistry analyser manufactured by ‘Abbott plc’) was also tested against material obtained from a national external quality assurance scheme (NEQAS).The time taken to produce POCT tests was calculated as the time elapsed (TE) between requesting tests, and the time at which completed results were returned to the ICE system. Patient waiting times were derived from the patient administration system (Symphony) used in the A&E department. To assess the true effect of POCT on patient waiting times the analysis was confined to cases associated with POCT tests only (n = 217). A control population (n=229) was randomly selected from the clinical laboratory database. The time interval between requesting a test and receiving the results for the POCT tests was 23 minutes and for the laboratory tests, 60 minutes. The patient waiting times (time of discharge - time of arrival) was 167 minutes for the POCT group and 208 for the clinical laboratory group, a difference of 31 minutes. The project confirmed that interfaced (on-line) POCT has many advantages with respect to the quality and safety of data management. The benefits include reliable identification of the requesting clinician and patient and the assurance that the right result is allocated to the right patient. The study also showed that the quality of results produced by the POCT devices met the requirements of the clinical environment.

Evaluation of the use of digital images for a national prostate core external quality assurance scheme

To evaluate the use of virtual images as an alternative to glass slides to expand the number of participants in the External Quality Assurance Scheme for prostatic biopsies. Benign and neoplastic cases, previously circulated as glass slides, were selected to include cases that had demonstrated a high level of agreement (n = 10) and a lesser degree of agreement (n = 10). Whole slide virtual images were circulated to 68 pathologists; 51 responses were returned. The levels of agreement for the primary diagnosis and for Gleason grading of cancers were analysed using kappa statistics. Responses for glass slides versus images were compared for the 24 pathologists for whom data were available. Levels of agreement for diagnostic categories using virtual slides were moderate to substantial, comparable to those found using glass slides. The level of agreement for Gleason grades 8-10 was substantial, but for lower grades was fair or moderate, poorer than for the glass slide circulation. Circulation of virtual images of biopsy material is a suitable alternative to glass slide-based schemes for the evaluation of diagnostic consistency. The majority of participants agreed that the ability to evaluate limited diagnostic material outweighed the disadvantages of a virtual system.

Cryoglobulin evaluation: best practice?

Cryoglobulins are serum immunoglobulins that precipitate at temperatures below 37 degrees C and re-dissolve on warming. Cryoglobulinaemia leads to variable symptoms including characteristic purpura, ischaemia of extremities, renal failure, peripheral neuropathy, abdominal pain secondary to intestinal ischaemia and arthralgias. Cryoglobulin testing is underutilized in clinical practice. It has been neglected in clinical laboratories and by clinicians due to several factors, such as the length of time it takes for serum cryoglobulin analysis to be performed in the laboratory, the perceived difficulty in getting optimal sampling conditions and a failure to appreciate that even apparently low levels of cryoglobulin can be associated with severe symptoms in some patients. The most important variable confounding standardization of cryoglobulin testing is improper sample handling. A recent report critically appraising the current practice of cryoglobulin evaluation in 137 laboratories in Europe by United Kingdom National External Quality Assurance Scheme (UKNEQAS) illustrated the wide variability in practice. Although many clinical laboratories perform cryoglobulin evaluation, there are widespread differences in the methodology used and the care with which this is carried out and this leads to considerable intralaboratory and interlaboratory variability. The most common sources of error are false-negative results due to loss of cryoprecipitate during transport and storage. Better standardization is needed to avoid missed diagnoses and improve the comparability of results. Laboratories should ensure that sample temperature is maintained at 37 degrees C until the serum is separated. In this article, we briefly review the classification and clinical features of cryoglobulins and suggest best practice guidelines for laboratory detection and identification of cryoglobulins.

External Quality Assurance Schemes: The Impact of Participation in the UK Versus Rest of the World: 5 Year Data from the UK National External Quality Assurance Scheme.

Abstract The American Society of Clinical Oncology/College of American Pathologists guidelines highlighted the critical importance of quality assurance in diagnostic testing for HER2.Unstained formalin-fixed, paraffin-embedded human breast carcinoma cell line sections were circulated to scheme participants on 15 occasions over 5 years. “Reference laboratories” reported results for the HER2/chromosome 17 ratio and HER2 copy number for 5 years for each cell line. Results from the 5th years participants (3 runs 13, 14, 15) were assessed for the pass rate in UK versus rest of the world (EU, US, Asia, etc). The number of participants was 76-78 laboratories/run (UK 30-35, ROW 43-46).Results: The percentage of laboratories achieving “appropriate” results ranged from 78-82% overall. Significantly higher performance was observed over 3 runs for UK laboratories (91-97%, “appropriate” results) versus ROW laboratories (67-74% “appropriate” results), p = 0.004. All methods used by scheme participants in UK Laboratories had excellent performance rates (Pathvysion, PharmDx, Ventana SISH/Inform, Kreatech Posieden). However in the ROW there was evidence of poor performance, which may be related to the assay format, although numbers of comparisons are relatively small.Participation in external quality assurance schemes is a valuable mechanism for evaluation and benchmarking of performance between laboratories. It also serves to improve consistency of HER2 testing by in situ hybridization. Using data from the UK NEQAS scheme we identified that laboratories whose performance is monitored and linked to an intergrated corrective action component(UK laboratories) perform consistently better than laboratories where performance data alone is provided (ROW). In the UK both participation and adequate performance in a national EQA scheme is required for laboratory accreditation. Whilst, in the context of robust EQA there is no evidence that different methods affect performance, in the ROW implementation of some assays appears sub-optimal. This poor performance does not, however, identify fundamental flaws with these methods, which are currently very well controlled amongst UK users but suggests greater attention to EQA results and change to improve laboratory performance is required in the rest of the world. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6010.

Quality Assurance in Her-2 Testing—Redefining the Gold Standard

The landscape of testing for human epidermal growth factor receptor 2 (Her-2)1 for breast cancer is changing rapidly. In 5 years we have moved from a test designed to predict the response to trastuzumab (Herceptin®) in patients with relapsed poor-prognosis disease to the position where deciding whether fit women with early breast cancer should be given adjuvant chemotherapy is based in part on this test result (1). Because adjuvant chemotherapy confers a survival benefit for approximately 10% of women treated and therefore produces little or no benefit and at least short- to medium-term harm to the other 90%, we need to be certain that our tests are reliable. It is also imperative that the laboratory data on which trial outcomes are judged are absolutely reliable. Sadly, this standard cannot be applied to Her-2 testing at the present time. Xiao and colleagues in the current issue of the Journal (2) have laid out new standards for Her-2 testing that should pave the way for a stepwise increase in quality in this area and supply a paradigm for testing other therapeutically important indicators in cancer management. A brief appraisal of current Her-2 testing practice worldwide will help to place the contribution of Xiao et al. in context. Her-2 testing is routinely carried out on primary breast cancers, either on the diagnostic core biopsy or on the excised tumor. Typically, such testing takes the form of an immunohistochemical (IHC) test on a tissue section, followed by fluorescence in situ hybridization (FISH) analysis in IHC-equivocal cases. Data from the UK National External Quality Assurance Scheme (NEQAS) audit for 2007 show …

HER2: Closing the Gap Between Laboratory Testing and Clinical Practice

Laboratory testing for human epidermal growth factor receptor 2 (HER2) status is critically important for the management of care of patients with breast cancer, especially for therapeutic decision making.1 Although the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines reaffirmed the importance of quality assurance in diagnostic testing for the HER2 gene and its protein product,2 a recent UK National External Quality Assurance Scheme (NEQAS) on HER2 testing by in situ hybridization showed modest performance, in that the percentage of laboratories achieving “appropriate” results ranged from 45% to 88%, whereas the percentage achieving “inappropriate” results ranged from 5% to 29%.3 Recent technological developments have created a new generation of laboratory diagnostics, sometimes identified with the term “omics,” which holds promise for better means of detecting diseases and monitoring response to treatment. However, as regards laboratory testing, there is evidence that not only recent research findings but also “old” research outcomes have simply been “lost in translation.”4 This, in turn, stresses the need for a more effective process to carry on translational research, involving also laboratory professionals. Recently, the need was emphasized for establishing an international collaboration to set standards and methods to evaluate laboratory diagnostic tests, primarily in terms of analytic performance, but also considering their clinical validity, clinical usefulness, and, finally, ethical and social implications. The story of HER2 testing well illustrates the evidence gap between diagnostic testing and clinical practice, unveiling the problems of reliability, accuracy, and standardization of diagnostic tests. More intriguingly, however, it highlights the need for correct interpretation and use of laboratory information, which are still areas of major improvement in diagnostics. An interesting lesson we have recently learned from HER2 testing is that only invasive testing, immunohistochemical analysis or fluorescence in situ hybridization (FISH), on human tissues has …

HER2 testing in the UK: further update to recommendations

These guidelines update the previous UK HER2 testing guidelines and have been formulated to give advice on methodology, interpretation and quality assurance to ensure that HER2 testing results are accurate,...

Prostatic pathology reporting in the UK: development of a national external quality assurance scheme

To develop a baseline picture of prostatic pathology reporting in the UK, identify areas of particular difficulty and assess the feasibility of a national external quality assurance scheme based on prostatic biopsy specimens using the same format as the National Health Service breast pathology scheme, as recommended by the National Institute for Clinical Excellence. Eight expert uropathologists and 32 randomly selected pathologists participated in four circulations each of 12 cases of prostatic biopsy specimens. A fixed text proforma was developed and responses were analysed for interobserver agreement using kappa statistics. Consistency of reporting the main diagnostic categories of benign and invasive carcinoma was good (kappa values 0.77 and 0.88, respectively), but only after excluding 19% of cases for which the experts did not reach 75% agreement. Areas of difficulty included the diagnosis of high-grade prostatic intraepithelial neoplasia and small foci of cancer. Prognostic factor reporting was more variable, with lower overall kappas for the assessment of Gleason grading (experts 0.55, others 0.50), perineural invasion (experts 0.64, others 0.50) and number of positive cores (experts 0.74, others 0.61). Given the difficulties in diagnosis of prostatic biopsy specimens and the assessment of prognostic factors, the expansion of the scheme could deliver important educational benefits.

Technical variations in prostatic immunohistochemistry: need for standardisation and stringent quality assurance in PSA and PSAP immunostaining

Aims: To assess variations in prostate specific antigen (PSA) and prostate specific acid phosphatase (PSAP) immunohistochemistry with particular reference to the antibody type (monoclonal or polyclonal) and the tissues used...

The use and therapeutic drug monitoring of teicoplanin in the UK.

Teicoplanin dosage recommendations for specific infections have been modified in recent years. However, there was no significant increase in the proportion of pre-dose concentrations > 20 mg/L between 1994 and 1998 in samples sent for teicoplanin assay at the Regional Antimicrobial Reference Laboratory, Bristol, UK. A questionnaire on the use of teicoplanin and therapeutic drug monitoring (TDM) was sent to all UK National External Quality Assurance Scheme antibiotic assay users. Teicoplanin was widely used in the UK, although vancomycin was more popular as a choice of glycopeptide. Fewer than 25% recommended teicoplanin TDM during routine use, the main reasons being perceived lack of toxicity and lack of evidence for the use of teicoplanin TDM. Pre-dose concentrations < 20 mg/L were considered appropriate for treatment of bacteraemia caused by methicillin-resistant Staphylococcus aureus by 53% of those responding. Data sheet advice was relied upon more than TDM as an indication of therapeutic dosing. Microbiologists who mainly used vancomycin tended to perform more TDM and seek higher serum concentrations when using teicoplanin than those who preferentially used teicoplanin.

External Quality Assessment for biochemical markers of myocardial damage: an Italian experience

In 1999 the Centre of Biomedical Research (CRB) in co-operation with the Italian interdisciplinary and intersociety Working Group on Markers of Myocardial Damage proposed a national external quality assurance scheme that was granted in accordance with the UK Clinical Pathology Accreditation Standards in 2001. The scheme, which stresses the importance of educational aspects in quality assurance, was scientifically designed to ensure that it would provide an objective assessment of participants' performance and promote quality improvements to meet the needs of participants. The present paper reports on the data collected in EQA cycles conducted to evaluate improvements in the performance of participants and in related methods. The findings obtained demonstrate that during the 4-year experience the scheme provided opportunities to improve the performance of laboratories and promoted an efficient, more satisfactory approach to analytical aspects. The number of unacceptable performances decreased from 11.6% to 5.6% for troponin I, from 19.5% to 9.0% for myoglobin and from 13.2% to 4.3% for creatine kinase myocardial isoenzyme (CK-MB). During cycles in 2001 and 2002, inter-variability (coefficient of variation, CV%) data for all markers appeared satisfactory and showed a significant improvement (lower than 10%), in particular for procedures automated on Dade Behring Dimension and Beckman Access systems. However, reference values/decisional limits declared by laboratories and those suggested by the manufacturers are not comparable, even within the same diagnostic system. The findings demonstrate that participation in EQA schemes provided an opportunity for participating laboratories to continuously improve the quality of their services.

Resistencia a antibióticos en 622 Streptococcus pneumoniae aislados de líquido cefalorraquídeo y sangre en 33 hospitales españoles de la Red Europea de Vigilancia de Resistencia a Antibióticos (2000)

In 1998 the European Union founded the European Antimicrobial Resistance Surveillance System (EARSS) for the control of antimicrobial resistance in invasive pathogens. This report present the results obtained for S. pneumoniae in the year 2000 in Spain. Participants included 33 hospitals covering approximately 25% of the Spanish population. The laboratories carried out isolation, identification and sensitivity studies with their usual methods. Quality control was performed by the UK National External Quality Assurance Scheme (NEQAS). A form was filled out with clinical information on the patient and data on the hospital, department and specimen isolated. This information was entered in a central database for analysis and validation by the Whonet.5 program. Invasive S. pneumoniae was isolated in 622 patients. Overall incidence was 6.4 cases/100,000 inhabitants. Among the strains isolated, 33.1% (CI 95%: 29.6-37) showed resistance to penicillin (22.2% intermediate; 10.9% resistant); 11% showed resistance to cefotaxime (10.1% intermediate; 0.9% resistant); and 21.1% were resistant to erythromycin. Erythromycin resistance was 7% in penicillin-sensitive strains and 46.4% in penicillin-resistant strains (p < 0.001). A total of 51.7% of strains were resistant to penicillin in children < or = 4 years old, as compared to 29% in patients > 4 years old (p < 0.001). A ciprofloxacin MIC > 2 mg/L was found for 2.4% of isolates. Penicillin resistance in invasive S. pneumoniae in Spain is among the highest in the European Union. The decrease in sensitivity to penicillin was significantly associated with cefotaxime and erythromycin resistance. Children < or = 4 years old have a significantly higher risk than adults of acquiring infection with strains resistant to penicillin, cefotaxime and erythromycin.