European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay.

BACKGROUND: International recommendations highlight the superior value of cardiac troponins (cTns) for early diagnosis of myocardial infarction along with analytical requirements of improved precision and detectability. In this multicenter study, we investigated the analytical performance of a new high sensitive cardiac troponin I (hs-cTnI) assay and its 99th percentile upper reference limit (URL). METHODS: Laboratories from nine European countries evaluated the ARCHITECT STAT high sensitive troponin I (hs-TnI) immunoassay on the ARCHITECT i2000SR/i1000SR immunoanalyzers. Imprecision, limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ) linearity of dilution, interferences, sample type, method comparisons, and 99th percentile URLs were evaluated in this study. RESULTS: Total imprecision of 3.3%-8.9%, 2.0%-3.5% and 1.5%-5.2% was determined for the low, medium and high controls, respectively. The lowest cTnI concentration corresponding to a total CV of 10% was 5.6 ng/L. Common interferences, sample dilution and carryover did not affect the hs-cTnI results. Slight, but statistically significant, differences with sample type were found. Concordance between the investigated hs-cTnI assay and contemporary cTnI assay at 99th percentile cut-off was found to be 95%. TnI was detectable in 75% and 57% of the apparently healthy population using the lower (1.1 ng/L) and upper (1.9 ng/L) limit of the LoD range provided by the ARCHITECT STAT hs-TnI package insert, respectively. The 99th percentile values were gender dependent. CONCLUSIONS: The new ARCHITECT STAT hs-TnI assay with improved analytical features meets the criteria of high sensitive Tn test and will be a valuable diagnostic tool.

A-B-3-Associations and dissociations of reading and arithmetic: Is domain-specific prediction outdated?

Reading and arithmetic are core domains of academic achievement with marked impact on career opportunities and socioeconomic status. While associations between reading and arithmetic are well established, evidence on underlying mechanisms is inconclusive. The main goal of this study was to reevaluate the domain-specificity of established predictors and to enhance our understanding of the (co-)development of reading and arithmetic. In a sample of 885 German-speaking children, standard domain-specific predictors of reading and arithmetic were assessed before and/or at the onset of formal schooling. Reading and arithmetic skills were measured at the beginning and end of second grade. Latent variables were extracted for all relevant constructs: Grapheme-phoneme processing (phonological awareness, letter identification), RAN (RAN-objects, RAN-digits), number system knowledge (number identification, successor knowledge), and magnitude processing (non-symbolic and symbolic magnitude comparison), as well as the criterion measures reading and arithmetic. Four structural equation models tested distinct research questions. Grapheme-phoneme processing was a specific predictor of reading, and magnitude processing explained variance specific to arithmetic. RAN explained variance in both domains, and it explained variance in reading even after controlling for arithmetic. RAN and number system knowledge further explained variance in skills shared between reading and arithmetic. Reading and arithmetic entail domain-specific cognitive components, and they both require tight networks of visual, verbal, and semantic information, as reflected by RAN. This perspective provides a useful background to explain associations and dissociations between reading and arithmetic performance.

Benchmarking diagnostic laboratory performance: Survey results for Germany, Austria, and Switzerland.

BACKGROUND AND AIMS: The need for patient safety through consistent diagnostic performance has increasingly been brought into focus during the last two decades. Around the globe operational efficiency of diagnostic laboratories plays a key role in satisfying this need, which has impressively been shown during the recent months of the SARS-CoV­2 pandemic. On a global level, however, there has been a lack to collate and benchmark data for diagnostic laboratories. The goals of this study were to design and pilot a questionnaire addressing key aspects of diagnostic laboratory management. METHODS: The questionnaire was designed using an iterative process and taking into consideration information that could be extracted from the literature, author experience and feedback from informal focus groups of laboratory professionals. The resulting tool consisted of 50 items, either relating to general information or more specifically addressing the topics of "operational performance", "integrated clinical care performance", and "financial sustainability". A limited number of laboratories were surveyed to be able to further improve the newly developed tool and motivate the global laboratory community to participate in further benchmarking activity. RESULTS AND CONCLUSION: Altogether, 65 laboratories participated in the survey, 42 were hospital laboratories and 23 were commercial laboratories. Potential for further improvement and standardization became apparent across the board, e.g. use of IT for order management, auto-validation, or turn-around time (TAT) monitoring. Notably, a gap was identified regarding services provided to physicians, in particular "reflexive test suggestions", "proactive consultation on complex cases", and "diagnostic pathways guidance", which were only provided by about two thirds of laboratories. Concordantly, within-laboratory TAT (Lab TAT) was monitored by about 80% of respondents, while sample-to-result TAT, which is arguably the TAT most relevant to clinicians, was only monitored by 32% of respondents. Altogether, the need for stronger integration of the laboratory into the clinical care process became apparent and should be a main trajectory of future laboratory management.

Drawing and handedness of preschoolers: a repeated-measurement approach to hand preference.

This study investigated handedness and drawing by preschoolers. An observational method for repeated measurement of hand preference is presented. A sample of 381 children (191 girls, 190 boys) ranging in age from 48 to 71 mo. was tested for drawing and hand preference on 14 tasks. Consistent hand preference was defined as always using a particular hand (left or right) for the same task. Girls with consistent hand preference showed better drawing scores compared to girls with inconsistent hand preference. The results showed the importance of a reliable method for measuring hand preference within a single task as early as preschool age.

Analytical Performance of 10 High-Volume Clinical Chemistry Assays on the Alinity c System.

BACKGROUND: Early access for routine testing with the Alinity c clinical chemistry system (Abbot Laboratories) presented the opportunity to characterize the analytical performance of multiple analytes across clinical laboratories in Europe. METHODS: A total of 8 laboratories from 7 European countries evaluated 10 high-volume chemistry assays on the Alinity c system for imprecision, linearity, and accuracy by method comparison to the routine ARCHITECT (Abbott Laboratories) method. RESULTS: Within-run precision was less than 4% coefficient of variation (CV), with total imprecision less than 5.6% CV for 5- and 20-day evaluations. Linearity met expectations, and method comparison showed strong correlation between the Alinity and ARCHITECT methods, with overall linear correlation coefficient between 0.980 to 1.000 and slopes of the regression line between 0.963 and 1.034. Mean percentage difference between the results of assays run on the ARCHITECT and the Alinity ranged between -1.7% and 2.15%. CONCLUSIONS: Our results demonstrated acceptable key analytical performance across all assays tested at each participating laboratory.

Reliable and Valid Coding of Thin Slices of Video Footage: Applicability to the Assessment of Mother-Child Interactions.

When using behavioral-observation methods for coding video footage, it is unknown how much time of an interaction needs to be coded to gain results that are representative for the behavior of interest. The current study examined this problem using the INTAKT, a standardized observational measure for assessing the quality of mother-child interactions. Results from coding only 10 min of each video (i.e., thin slices) were compared with results from coding the remaining parts (averaging about 40 min) of the interaction. Inter-rater agreement for the short versions taken from the beginning or the middle, but not the end of the interactions indicated satisfactory observer accuracy. Coding results did not differ between short and long video sequences, when sequences were taken from the middle of the interactions. Importantly, characteristic differences between different interactive situations were equally well represented in the short and long video sequences. Therefore, our results show that coding only 10 min of an interaction is as reliable and valid as coding full-length videos, if those short sequences are taken from the middle of an interaction. Our findings support the idea that for every method, it is necessary to individually determine the window duration that is long enough to gain results that are reliable and valid.

No evidence of hepatitis B virus activity in patients with anti-HBc antibody positivity with or without anti-hepatitis C virus antibody positivity.

BACKGROUND: The serological pattern of anti-HBc antibody positivity without both, HBsAg and anti-HBs antibody positivity may be present in up to 4% of the population of Europe and the United States. OBJECTIVES: The aim of the present study was to determine the hepatitis B virus (HBV) activity by detection of serum HBV DNA in patients with anti-HBc antibody positivity only and with confirmed anti-hepatitis C virus (anti-HCV) antibody positivity or without anti-HCV antibody positivity. STUDY DESIGN: A total of 141 patients positive for anti-HBc antibodies only, were investigated on serum HBV DNA load. Patients were classified into two groups: patients with confirmed positive anti-HCV antibodies (group 1) and patients without anti-HCV antibodies (group 2). RESULTS: Demographic data of patient groups were similar. In 66 of 70 patients with anti-HBc antibodies and anti-HCV antibodies (group 1), serum HCV RNA was detected; the remaining 4 patients were HCV RNA negative but the presence of anti-HCV antibodies was confirmed by the line probe assay. In none of the patients, with anti-HBc antibodies and without anti-HCV antibodies (group 2), serum HCV RNA was detected. In none of the patients, serum HBV DNA was detected. CONCLUSION: In this study, serum HBV DNA could not be detected in patients with anti-HBc antibodies only. There seems to be no need for determination of serum HBV DNA in patients without clinical evidence of chronic liver disease. Nevertheless, it would be useful to test patients with progressive liver disease and those, which belong to high-risk groups such as hemophiliacs, intravenous drug abusers, patients on hemodialysis, and immunocompromised patients.

Hepatitis B virus activity in patients with anti-hepatitis C virus antibody positivity and hepatitis B antigen positivity.

BACKGROUND: Co-infection with hepatitis B virus (HBV) and HCV seems to be relatively frequent. There might be a mutual influence on replication activity of HBV and HCV. OBJECTIVES: To determine the HBV activity in patients with serum HCV RNA and HBsAg positivity and in those with confirmed anti-HCV antibody and HBsAg positivity but serum HCV RNA negativity. STUDY DESIGN: A total of 1,200 anti-HCV antibody positive samples were investigated. Samples of HCV RNA and HBsAg positive patients were compared with those of confirmed anti-HCV and HBsAg positive but serum HCV RNA negative patients. HBV activity was tested with the quantitative Cobas Amplicor HBV Monitor Test (Roche Diagnostic Systems, Pleasanton, CA). RESULTS: Of all studied patients with chronic hepatitis C (serum HCV RNA positivity) only 1.0% were found to be HBsAg positive. In contrast, of all patients with confirmed anti-HCV positivity but serum HCV RNA negativity, 11.9% tested HBsAg positive. The median of HBV DNA levels of patients with serum HCV RNA positivity and HBeAg seroconversion (4.0 x 10(2) HBV DNA copies per ml) was found to be slightly lower than that of patients with serum HCV RNA negativity and HBeAg seroconversion (2.5 x 10(3) HBV DNA copies per ml; P>0.05). The median of HBV DNA levels of patients with serum HCV RNA positivity but without HBeAg seroconversion (1.1 x 10(4) HBV DNA copies per ml) was found to be significantly lower than that of patients with serum HCV RNA negativity but without HBeAg seroconversion (2.6 x 10(7) HBV DNA copies per ml; P<0.05). CONCLUSION: A mutual effect on HBV and HCV replication could be observed. The molecular assay for quantification of serum HBV DNA was found to be useful for the routine diagnostic laboratory.

HLA-DR as a marker for increased risk for systemic inflammation and septic complications after cardiac surgery.

OBJECTIVE: This study investigated the predictive value of a decrease in monocyte HLA-DR expression as an early marker for postoperative SIRS and septic complications. We hypothesized that decreased HLA-DR levels in the first 24 h after cardiac surgery is not related to postoperative SIRS/sepsis. We also compared HLA-DR levels of patients with postoperative complications to those with an uncomplicated course. DESIGN AND SETTING: Prospective observational study in a tertiary care postoperative intensive care unit. PATIENTS: Eighty five consecutive patients undergoing cardiac surgery. MEASUREMENTS AND RESULTS: Expression of HLA-DR on monocytes was analyzed by flow cytometry using a new quantitative and well standardized technique. Arterial blood samples were collected before induction of anesthesia, immediately after admission to the ICU, and on the first postoperative day. Postoperative HLA-DR expression was significantly decreased in all patients. There were no significant differences in HLA-DR expression during the first 24 h after surgery in patients with uncomplicated course and those developing SIRS or septic complications. CONCLUSIONS: In patients undergoing cardiac surgery the monitoring of pre- and immediate postoperative HLA-DR levels during the first 24 h does not help to predict increased risk for postoperative SIRS/sepsis or infectious complications.

[The enhancement of development at nursery school age]. / Entwicklungsförderung im Kindergartenalter.

A scientifically based synthesis of diagnostic inventaries and intervention measures would be desirable for the practice of the enhancement of development. Recent research on preschool training, however, has hitherto tended to deal with the development and testing of the effectiveness of training programmes without linking them explicitly to a diagnosis of the abilities which are to be promoted. This article presents two studies that are part of a major project to connect the assessment and enhancement of development. The objective was to develop and empirically test intervention measures for two functional areas of the Wiener Entwicklungstest (WET, Kastner-Koller and Deimann 1998, 2002). Two training conditions were developed for the area of language, i.e. a specific encouragement of vocabulary and conceptualisation and general linguistic promotion. Similarly, two different promotion strategies were realized for the functional area Visual Perception, i.e. a conventional means of promotion using work sheets and a form of promotion utilizing games. According to area, these treatments were tested for their differential effectiveness in an experimental design (linguistic training N = 42; training of perception N = 51), using the Wiener Entwicklungstest (WET) for the pre- and posttests, the intermediate programme comprising 16 units and a control group meantime taking part in the educational programme of the nursery school in both studies. The results showed that both forms of linguistic training and the promotion of perception through games were highly effective in their areas, but that the effect of work sheets could not be definitively assessed. The different effects of the training programmes on children with and without a general developmental lag in the Wiener Entwicklungstest (WET) were particularly interesting.

EC4 European Syllabus for Post-Graduate Training in Clinical Chemistry and Laboratory Medicine: version 3 - 2005.

The EC4 Syllabus for Postgraduate Training is the basis for the European Register of Specialists in Clinical Chemistry and Laboratory Medicine. The syllabus: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. The syllabus is not primarily meant to be a training guide, but on the basis of the overview given (common minimal programme), national societies should formulate programmes that indicate where knowledge and experience is needed. The main points of this programme are: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. Knowledge in biochemistry, haematology, immunology, etc.; Pre-analytical conditions; Evaluation of results; Interpretations (post-analytical phase); Laboratory management; and Quality insurance management. The aim of this version of the syllabus is to be in accordance with the Directive of Professional Qualifications published on 30 September 2005. To prepare the common platforms planned in this directive, the disciplines are divided into four categories: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. Knowledge in biochemistry, haematology, immunology, etc.; Pre-analytical conditions; Evaluation of results; Interpretations (post-analytical phase); Laboratory management; and Quality insurance management. General chemistry, encompassing biochemistry, endocrinology, chemical (humoral), immunology, toxicology, and therapeutic drug monitoring; Haematology, covering cells, transfusion serology, coagulation, and cellular immunology; Microbiology, involving bacteriology, virology, parasitology, and mycology; Genetics and IVF.

N-terminal pro-B-type natriuretic peptide as an indicator of possible cardiovascular disease in severely obese individuals: comparison with patients in different stages of heart failure.

BACKGROUND: Mild stages of heart failure might be difficult to diagnose in severely obese individuals with a body mass index (BMI) >40 kg/m(2). Measurement of the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is feasible for detecting cardiac impairment. The aims of our study were to measure NT-proBNP in plasma of severely obese patients and to compare the results with results for patients in different stages of manifest cardiac dysfunction. METHODS: In 61 severely obese individuals (median BMI, 43.2 kg/m(2)) and 96 nonobese patients with existing heart failure [classified into New York Heart Association (NYHA) classes I-IV], NT-proBNP was measured in the fasting condition. A medical history, physical examination, electrocardiography, blood chemistry, and chest x-ray were performed in the obese group. In addition, echocardiography was performed in the NYHA group. RESULTS: In obese individuals, NT-proBNP was increased to a median of 356 (interquartile range, 221-458) pmol/L [854 (530-1099) ng/L] and was comparable (P >0.05) to the median value for NYHA I patients {289 (258-451) pmol/L [694 (619-1082) ng/L]}, but was significantly lower than in the other NYHA groups (P <0.001 for each). CONCLUSION: The prognostic relevance of increased NT-proBNP for risk of developing cardiac insufficiency in severely obese patients needs to be further evaluated.

Passive immunization with the anti-HIV-1 human monoclonal antibody (hMAb) 4E10 and the hMAb combination 4E10/2F5/2G12.

OBJECTIVES: To study the safety, immunogenicity and pharmacokinetics of the human monoclonal antibody (hMAb) 4E10 alone and in combination with the hMAbs 2F5 and 2G12 in HIV-1-infected persons. MATERIALS AND METHODS: Eight healthy volunteers with > or =350 CD4 cells/mm3 and < or =100 000 HIV-1 RNA copies/mL were enrolled, seven finished the study. A single 4E10 infusion was administered on day 0, followed by three doses of the hMAb combination 4E10/2F5/2G12 on days 7, 14 and 21 (total amount 8.5 g). Safety was assessed by physical examination, blood chemistry, complete blood cell count and recording of adverse events. 4E10, 2F5 and 2G12 plasma levels were determined before and at the end of each infusion and during the 7 week follow-up. RESULTS: No drug-related adverse events were observed throughout the study. The median plasma concentrations immediately after the first infusion were 371, 253 and 139 microg/mL for 4E10, 2F5 and 2G12. Multiple infusions resulted in maximum plasma concentrations of 407, 294 and 210 microg/mL for 4E10, 2F5, and 2G12, respectively. The median elimination half-lives (t1/2beta) were 6.6, 3.2 and 14.1 days for 4E10, 2F5 and 2G12. A low level antibody response against 2G12 was found in two patients. CONCLUSION: This Phase I trial showed that the hMAb 4E10 can be safely administered, both alone and in combination with 2F5 and 2G12 to HIV-1-infected patients.

Effect of gastric banding on aminoterminal pro-brain natriuretic peptide in the morbidly obese.

OBJECTIVE: Aminoterminal pro-brain natriuretic peptide (NT-proBNP), like brain natriuretic peptide, might have diagnostic utility in detecting left ventricular hypertrophy and/or left ventricular dysfunction. The aim of the study was to investigate the relationship between morbid obesity and NT-proBNP and the effect of weight reduction on this parameter. RESEARCH METHODS AND PROCEDURES: A total of 34 morbidly obese patients underwent laparoscopic adjustable gastric banding (LAGB). NT-proBNP levels were measured before and 12 months after the surgery. RESULTS: Metabolic features and systolic and diastolic blood pressure were significantly decreased (p < 0.00001 for both) after a cumulative weight loss of 19.55 kg 1 year after LAGB. NT-proBNP concentration was significantly higher in morbidly obese patients before LAGB than in normal-weight control subjects (341.15 +/- 127.78 fmol/mL vs. 161.68 +/- 75.78 fmol/mL; p < 0.00001). After bariatric surgery, NT-proBNP concentration decreased significantly from 341.15 +/- 127.78 fmol/mL to 204.87 +/- 59.84 fmol/mL (p < 0.00001) and remained statistically significantly elevated (204.88 +/- 59.84 fmol/mL vs. 161.68 +/- 75.78 fmol/mL; p = 0.04) compared with normal-weight subjects. DISCUSSION: This investigation demonstrates higher levels of NT-proBNP in morbidly obese subjects and a significant decrease during weight loss after laparoscopic adjustable gastric banding. In obesity, NT-proBNP might be useful as a routine screening method for identifying left ventricular hypertrophy and/or left ventricular dysfunction.

The practice of clinical chemistry in the European Union.

The European Communities Confederation of Clinical Chemistry has been actively engaged in raising the level of clinical chemistry in the European Union. Closer contacts between the national societies for clinical chemistry have resulted in more comparable programs for postgraduate training of clinical chemists, closer similarity of contents and practice of the profession in the different countries, and the official registration of professionals. This article reviews some of the characteristics of professional organisation, practice, and regulation in the fifteen European Union countries. Many similarities appear. In half of the countries microbiology, blood-banking and transfusion medicine fall within the domain of clinical chemistry. The minimum number of years for training (university and postgraduate) is eight, but in practice this will extend to 10 or more years. Official regulation of the profession by law exists in a minority of countries. Continuing education and re-registration have not been officially instituted yet in any country, but these issues will be the next steps forward. In those countries that prepare themselves for entering the European Union, training and practice of clinical chemistry are moving towards the common standards of the European Communities Confederation of Clinical Chemistry.

The European Register for Specialists in Clinical Chemistry and Laboratory Medicine: guide to the Register Version 2-2003 and procedure for re-registration.

The European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) opened a Register for European Chemists in 1997. The operation of the Register is undertaken by a Register Committee (EC4RC). During the last 5 years more than 1,400 clinical chemists entered the register. In this article an update of the first Guide to the Register is given, based on the experience of 5 years of operation and the development of the discipline. The registration is valid for 5 years. In a second part the procedure and the conditions for re-registration are presented.