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Quantitative morphometry of hippocampal pyramidal cells: differences between anatomical classes and reconstructing laboratories.

The dendritic trees of hippocampal pyramidal cells play important roles in the establishment and regulation of network connectivity, synaptic plasticity, and firing dynamics. Several laboratories routinely reconstruct CA3 and CA1 dendrites to correlate their three-dimensional structure with biophysical, electrophysiological, and anatomical observables. To integrate and assess the consistency of the quantitative data available to the scientific community, we exhaustively analyzed 143 completely reconstructed neurons intracellularly filled and digitized in five different laboratories from 10 experimental conditions. Thirty morphometric parameters, including the most common neuroanatomical measurements, were extracted from all neurons. A consistent fraction of parameters (11 of 30) was significantly different between CA3 and CA1 cells. A considerably large number of parameters was also found that discriminated among neurons within the same morphological class, but reconstructed in different laboratories. These interlaboratory differences (8 of 30 parameters) far outweighed the differences between experimental conditions within a single lab, such as aging or preparation method (at most two significant parameters). The set of morphometrics separating anatomical regions and that separating reconstructing laboratories were almost entirely nonoverlapping. CA3 and CA1 neurons could be distinguished by global quantities such as branch order and Sholl distance. Differences among laboratories were largely due to local variables such as branch diameter and local bifurcation angles. Only one parameter (a ratio of branch diameters) separated both morphological classes and reconstructing laboratories. Compartmental simulations of electrophysiological activity showed that both differences between anatomical classes and reconstructing laboratories could dramatically affect the firing rate of these neurons under different experimental conditions.

Action Potentials↗

A quality assessment survey of SNP genotyping laboratories.

To survey the quality of SNP genotyping, a joint Nordic quality assessment (QA) round was organized between 11 laboratories in the Nordic and Baltic countries. The QA round involved blinded genotyping of 47 DNA samples for 18 or six randomly selected SNPs. The methods used by the participating laboratories included all major platforms for small- to medium-size SNP genotyping. The laboratories used their standard procedures for SNP assay design, genotyping, and quality control. Based on the joint results from all laboratories, a consensus genotype for each DNA sample and SNP was determined by the coordinator of the survey, and the results from each laboratory were compared to this genotype. The overall genotyping accuracy achieved in the survey was excellent. Six laboratories delivered genotype data that were in full agreement with the consensus genotype. The average accuracy per SNP varied from 99.1 to 100% between the laboratories, and it was frequently 100% for the majority of the assays for which SNP genotypes were reported. Lessons from the survey are that special attention should be given to the quality of the DNA samples prior to genotyping, and that a conservative approach for calling the genotypes should be used to achieve a high accuracy.

Clinical Laboratory Techniques↗

Effect of type of screening laboratory on population-based occurrence of cervical lesions in Finland.

The incidence of cervical cancer decreased in Finland over a 30-year period because of an effective screening program, but in the beginning of the 1990s it began to increase. Reasons for such an increase are variable: changes in sexual habits, shortcomings in attendance for screening and possibly variation in laboratory quality. We evaluated the impact of 3 laboratories in the greater Helsinki area on screening performance and on the incidence of invasive cervical cancer and preinvasive cervical lesions in the target population. We studied time trends, geographic differences in attendance and detection rates from screening and the incidence of invasive cancer in the greater Helsinki area (population about 1 million) during the 1990s, when screening was reorganized from the Cancer Society of Finland laboratory to the municipal one (Helsinki) and to a private laboratory (Espoo), while in Vantaa screening remained with the same Cancer Society laboratory. The attendance rate for screening increased during the study period in all 3 cities. The numbers of cytologically suspected and histologically confirmed precancerous lesions found, including severe lesions, decreased significantly with the change of laboratory in Espoo; but in Helsinki and Vantaa, they increased. The overall incidence of invasive cervical cancer increased in all cities in the age groups screened but mostly in Espoo. The rather rapid changes and variation in trends in the number of screening findings cannot be explained by changes in etiologic factors or attendance. They may be related more to the quality of the laboratory performance and perhaps to the criteria used in cytology and colposcopy. A well-organized auditing system is proposed to maintain high quality in screening.

Adult↗

Initial impact of a clinical laboratory computer system. Themes common to expectations and actualities.

A longitudinal study is being conducted of a clinical laboratory computer information system's impact. This paper reports on effects that laboratory directors anticipated prior to installation, and effects reported by laboratory technologists 7 months postimplementation. Primary changes caused by the computer system were increases in the amount of paper work performed by technologists, and improvements in laboratory results reporting. The system generally was well accepted, but laboratory technologists differed in their responses to it. Technologists in some laboratories focused on work increases, whereas in other laboratories they emphasized improved information flow. The paper considers how changes in processes and outcomes of work might affect responses to a computer system. It also considers the implementation process, and suggests some areas where management could benefit from an improved understanding of responses to a computer information system.

Attitude of Health Personnel↗

Forecasting staffing needs for productivity management in hospital laboratories.

Daily and weekly prediction models are developed to help forecast hospital laboratory work load for the entire laboratory and individual sections of the laboratory. The models are tested using historical data obtained from hospital census and laboratory log books of a 90-bed southwestern hospital. The results indicate that the predictor variables account for 50%, 81%, 56%, and 82% of the daily work load variation for chemistry, hematology, and microbiology sections, and for the entire laboratory, respectively. Equivalent results for the weekly model are 53%, 72%, 12%, and 78% for the same respective sections. On the basis of the predicted work load, staffing assessment is made and a productivity monitoring system constructed. The purpose of such a system is to assist laboratory management in efforts to utilize laboratory manpower in a more efficient and cost-effective manner.

Efficiency↗

[Point-of-care-testing--the intensive care laboratory].

After successful centralization of laboratory analyses since more than 30 years, advances in biosensors, microprocessors, measurement of undiluted whole blood and miniaturization of laboratory analyzers are leading nowadays more and more to a re-decentralization in the laboratory medicine. Point-of-care-testing (POCT), which is defined as any laboratory test performed outside central or decentralized laboratories, is becoming more and more popular. The theoretical advantages of POCT are faster turn-around-times (TAT), more rapid medical decisions, avoidance of sample identification and sample transport problems and the need of only small specimen volumes. These advantages are frequently mentioned, but are not associated with a clear clinical benefit. The disadvantages of POCT such as incorrect handling and/or maintenance of the analyzers by nontrained clinical staff, inadequate or even absent calibrations and/or quality controls, lack of cost-effectiveness because of an increased number of analyzers and more expensive reagents, insufficient documentation and difficult comparability of the obtained POCT-results with routine laboratory results, are strongly evident. According to the authors' opinion the decision for the establishing of POCT has only to be made in a close co-operation between physicians and laboratorians in order to vouch for necessity and high quality of the analyses. Taking the local situation into consideration (24-h-central laboratory, etc.) the spectrum of parameters measured by means of POCT should be rigorously restricted to the vital functions. Such analytes should be: hemoglobin or hematocrit, activated whole blood clotting time, blood gases, sodium, potassium, ionized calcium, glucose, creatinine, ammonia and lactate.

Clinical Laboratory Techniques↗

[The incorrect laboratory result. Part 1: Pre- and postanalytical phase].

Laboratory results play a key role in the diagnostic procedure, the decision of treatment and the follow up of diseases. A high validity of the laboratory result is an important precondition for the efficacy in clinical medicine. Analytical standards have been developed under strong quality control criteria, however, there are no sufficiently defined standards for the pre- and postanalytical phase in laboratory diagnostics. Thus, most of laboratory errors are caused by pre- and postanalytical mistakes. The competent knowledge of possible sources for laboratory errors is a critical precondition for their avoidance. Diagnostic sensitivity and specificity play an important role for the choice of a laboratory test, whereas the predictive value should be considered for the medical relevance of the test result. In addition, many interference factors, which may influence the results of the laboratory tests have to be considered as age, sex, race, lifestyle, drugs, pregnancy, specimen collection, quality and handling as well as special factors, which may influence the complex of immunological and molecular diagnostics.

Blood Chemical Analysis↗

A study of quality assessment in clinical microbiology performance of independent laboratories in Tokyo: 18-year participation in the Tokyo Metropolitan Government External Quality Assessment Program.

We evaluated the performance of independent microbiology laboratories in Tokyo over an 18-year period of participation in the external quality assessment (EQA) program, and we estimated the impact of the EQA program. The study design was a longitudinal retrospective analysis of performance, including isolation, identification, and antimicrobial susceptibility testing of bacteria from simulated patients' samples, in "open" surveys compared with "blind" surveys. Independent microbiology laboratories, licensed by the Tokyo Metropolitan Government, have been subject to mandatory evaluation by the EQA program since 1982. Survey reports, correspondence, annual guidance meetings, and inspections are used as quality improvement strategies. The performance for identification in "blind" surveys was significantly worse than that in "open" surveys (P < 0.001). Poorly performing laboratories had common features, including inadequate supervision by physicians and lack of familiarity with the impact of variations on the use of the standards. However, there were improvements in the performance of identification of some pathogens. The performance of susceptibility testing has not yet reached the relatively high level seen for identification. Some of the smaller laboratories have been gradually acquired by commercial chains operating outside Tokyo. The EQA program has established a role both in regard to laboratory improvement and as an educational tool. However, the program lags behind these of other developed countries in regard to the practical sciences. The main problems in regard to laboratory improvements are a shortage of human resources in clinical microbiology, lack of standardization of laboratory methods, and the pressures of financial constraints in the Japanese medical insurance system.

Data Collection↗

The isolation of fungi from laboratory dental pumice.

Samples of used dental laboratory pumice from the two dental laboratories were cultured for the isolation of fungi. The resulting supernatant fluid from sedimentation of each pumice sample after suspension in sterile saline was serially diluted and plated onto Sabouraud agar. After incubation, fungal colonies observed were enumerated, isolated, and identified. The mean number of fungal colonies recovered from 10 pumice samples in laboratories I and II was 51.0 X 10(2) and 22.6 X 10(2), respectively. In both laboratories the predominant fungi recovered were Aspergillus niger and Fusarium sp. Other fungi recovered included Cephalosporium and Penicillium species and A. flavus. Many of these organisms have been involved in human disease. It is suggested that the presence of fungi in used dental laboratory pumice presents an unhygienic condition in the dental laboratory and may place dental laboratory technicians and denture patients at increased risk of fungal sensitization and disease.

Aspergillus niger↗

Characteristics and capabilities of U.S. commercial toxicological testing laboratories.

About 800 commercial chemical testing laboratories were surveyed by telephone to determine how many provide toxicological testing services and what characteristics the toxicological testing laboratories portrayed. The survey identified 274 laboratories that performed toxicological testing in 1981. These are estimated to account for 94 to 98% of the toxicology laboratory population. The survey data provided a general profile of these laboratories, showed the number of laboratories capable of performing different types of tests, indicated the amount of excess capacity, and identified the most critical constraints to future expansion of testing. There were an estimated 180 laboratories providing mammalian toxicological tests, 150 providing in vitro tests, 150 providing environmental effects tests, and 140 providing chemical fate tests. At the time of the survey, the industry appeared able to do about 20% additional testing before reaching capacity.

Animals↗

Laboratory data predicts survival post hospitalization.

From a database of 93,077 in-patient admissions, patients assigned to catastrophic, very severe, moderately severe, and average 30-day mortality risk categories (as defined in Medicare Hospital Mortality Information, 1989 release, from the Health Care Financing Administration (HCFA] were selected for study. These admissions account for 30% of all admissions, but 70% of all deaths up to 1 year post admission. To determine whether laboratory information adds to the predictive power of the information used by HCFA, we compare the performance of 1 year survival predictors (Cox model) that use only diagnostic, demographic, and comorbidity information, with the performance of predictors that also include laboratory information. Using a separate set of patients not used for model definition, we find that laboratory data contain significant prognostic information independent of that already available in non-laboratory data. In HCFA's catastrophic disorders for example, non-laboratory information reduces the average risk of predicting a wrong outcome by 17% relative to considering only catastrophic group membership, and adding laboratory data reduces this risk by a further 21%. These improvements result primarily from considering the outcomes of a small set of routine laboratory tests (maximum BUN, AST, and WBC, and minimum CO2, hematocrit, and sodium).

Centers for Medicare and Medicaid Services, U.S.↗

Systematic reviews in laboratory medicine: principles, processes and practical considerations.

BACKGROUND: Systematic reviews and meta-analyses are generally accepted to represent the highest level of evidence, and are a cornerstone in practising evidence-based medicine. So far, these efforts have been largely confined to the evaluation of the efficacy and effectiveness of therapeutic and preventive interventions. Systematic reviews in laboratory medicine are scarce and many of them do not meet essential quality criteria [Clin. Chem. Lab. Med. 38 (2000) 577]. Most of these problems are related to the poor design and heterogeneity of primary research, and that there are no agreed methods or quality standards for making systematic reviews in laboratory medicine. AIMS AND OBJECTIVES: For better evidence in laboratory medicine, not only higher quality primary studies but also standardized methodologies for designing, conducting and reporting systematic reviews in diagnostics are needed. The aim of this review is to present the general principles and provide a step-by-step process of systematic reviewing in laboratory medicine. METHODS: This narrative review is based on the overview of the medical literature on the methodology of systematic reviewing and that of the "state of the art" of evidence-based diagnosis. RESULTS: Systematic reviews of diagnostic interventions differ from that of therapeutic interventions in the methods of question formulation, the choice of study design, the assessment of study quality and the statistical methods used to combine results. Therefore, the general principles of systematic reviewing are adapted to the specialist field of laboratory medicine. The process of systematic reviewing consists of six key steps: (1) preparation for the review, (2) systematic search of the primary literature, (3) selection of papers for review, (4) critical appraisal of the selected literature, (5) analysis and synthesis of data, and (6) interpretation of data. The most important technical and methodological aspects of each step and the essential elements of a good systematic review in laboratory medicine are presented. CONCLUSIONS: Systematic reviews of diagnostic interventions support clinical and policy decisions, the development of practice guidelines, clinical audit, technology assessment, economic evaluations, education and training, and identify gaps in our knowledge for future research. Systematic reviewing of laboratory data is expected to result in better, bigger and more reliable primary studies, which hopefully will support the diffusion of new diagnostic technologies with scientifically proven efficacy and effectiveness in the future.

Clinical Laboratory Techniques↗

Laboratory variables and stratification of metastatic colorectal cancer patients: recommendations for therapeutic trials and for clinical practice guidelines.

OBJECTIVE: To identify, through a systematic review of the literature, the laboratory variables that, in addition to performance status and to the degree of tumor invasion, would allow a more accurate stratification of metastatic colorectal cancer patients who participate in chemotherapy trials, with or without radiotherapy. SECONDARY AIM: To compare the results of our systematic review with the recommendations made in current clinical practice guidelines, and with the results of related systematic reviews. METHODS: Update of two recently published systematic reviews, without metaanalysis, following the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials statement. RESULTS: Of 877 publications retrieved, reasonable exclusion and inclusion criteria allow us to include 15 studies in our systematic review, thus confirming the low quality of clinical research in laboratory medicine. Four variables were most often found "significant" in multivariate statistical analysis: pretherapeutic levels of laboratory tests (13/15, 87%), degree of tumor invasion (9/13, 69%), treatment, or response to treatment (6/9, 67%), and performance status (8/13, 62%). The laboratory variable whose measurements are quite often recommended in the 10 clinical practice guidelines or in the four related systematic reviews that we retrieved are carcinoembryonic antigen (CEA), and liver function tests to a lesser extent. CONCLUSIONS: Available evidence supports the recommendation that in all metastatic colorectal cancer patients who participate in therapeutic trials, the following pretreatment laboratory variables should be systematically measured: blood cell counts, and haemoglobin, plasma prothrombin time, serum alkaline phosphatase (ALP), lactate dehydrogenase, transaminases, albumin, bilirubin, and CEA. If other tests were to be added, gamma glutamyl transferase, and erythrocyte sedimentation rate might perhaps be proposed. Further studies would be necessary to support the addition to this list, of other tests [e.g., cancer antigen (CA) 19-9]. Rather than using laboratory variables according to arbitrary thresholds, it seems recommendable to use them as continuous variables, and if possible, in terms of kinetics. Many clinical practice guidelines do not use levels of evidence in order to grade the strength of their recommendations, but rather seem to be based on experts opinions which are not always in agreement with the results of systematic reviews.

Antineoplastic Agents↗

The current status of forensic science laboratory accreditation in Europe.

Forensic science is gaining some solid ground in the area of effective crime prevention, especially in the areas where more sophisticated use of available technology is prevalent. All it takes is high-level cooperation among nations that can help them deal with criminality that adopts a cross-border nature more and more. It is apparent that cooperation will not be enough on its own and this development will require a network of qualified forensic laboratories spread over Europe. It is argued in this paper that forensic science laboratories play an important role in the fight against crime. Another, complimentary argument is that forensic science laboratories need to be better involved in the fight against crime. For this to be achieved, a good level of cooperation should be established and maintained. It is also noted that harmonization is required for such cooperation and seeking accreditation according to an internationally acceptable standard, such as ISO/IEC 17025, will eventually bring harmonization as an end result. Because, ISO/IEC 17025 as an international standard, has been a tool that helps forensic science laboratories in the current trend towards accreditation that can be observed not only in Europe, but also in the rest of the world of forensic science. In the introduction part, ISO/IEC 17025 states that "the acceptance of testing and calibration results between countries should be facilitated if laboratories comply with this international standard and if they obtain accreditation from bodies which have entered into mutual recognition agreements with equivalent bodies in other countries using this international standard." Furthermore, it is emphasized that the use of this international standard will assist in the harmonization of standards and procedures. The background of forensic science cooperation in Europe will be explained by using an existing European forensic science network, i.e. ENFSI, in order to understand the current status of forensic science in Europe better. The Council of Europe and the European Union approaches to forensic science will also be discussed by looking at the legal instruments and documents published by these two European organizations. Data collected from 52 European forensic science laboratories will be examined and findings will be evaluated from a quality assurance and accreditation point of view. The need for harmonization and accreditation in forensic science will be emphasized. The steps that should be taken at the European level for increasing and strengthening the role of European forensic science laboratories in the fight against crime will be given as recommendations in the conclusion.

Accreditation↗

Reliability of extracranial carotid artery duplex ultrasound scanning: value of vascular laboratory accreditation.

OBJECTIVES: The purpose of this study was to evaluate the reliability of carotid duplex ultrasound scanning performed by nonaccredited vascular laboratories and to assess the clinical effect on patient management. METHODS: We retrospectively reviewed concordance of findings of carotid duplex ultrasound scanning between laboratories accredited by the Intersocietal Commission for Accreditation of Vascular Laboratories and nonaccredited laboratories in 174 patients with asymptomatic disease referred to tertiary care community hospitals for surgical evaluation for carotid endarterectomy (CEA) between January 2001 and December 2002, and evaluated changes in clinical management made on the basis of repeat examinations. RESULTS: Concordant findings were noted in 171 of 348 arteries (49%), predominantly those with minimal or mild disease (114 arteries; 67%). Discordant findings of no clinical significance were found in 54 arteries (16%). Clinically significant discordant findings were noted in 123 arteries (35%) in 107 patients (61%). In 104 arteries (88 patients) stenosis was overestimated by the nonaccredited laboratory secondary to technical error (19 arteries), use of B-mode imaging data alone (36 arteries), and use of inappropriate velocity criteria (49 arteries). None of these patients underwent CEA. Stenosis was significantly underestimated in 19 arteries (19 patients); all of these patients underwent uncomplicated CEA. CONCLUSIONS: Incorrect physician interpretation of data is the most common cause of error in carotid duplex ultrasound scanning performed in nonaccredited vascular laboratories. Results of carotid duplex ultrasound scanning from nonaccredited laboratories should be considered with extreme caution, and do not appear reliable in planning treatment of obstructive disease.

Accreditation↗

Performance of a point-of-care qualitative triple cardiac marker screen under controlled laboratory conditions and in an emergency department setting.

BACKGROUND: The performance of point-of-care testing under controlled laboratory conditions may vary from results obtained in actual patient care settings. User errors are a major cause of this discrepancy. METHODS: We studied the clinical performance of the Cardiac STATus (Spectral USA, Frederick, MD), a qualitative triple cardiac marker point-of-care test, under controlled laboratory conditions and in actual practice in an emergency department (ED) satellite laboratory. First-draw samples obtained from patients presenting to the hospital emergency department with chest pain were used for the study. Tests were performed in the chemistry research laboratory by a company product specialist or in an emergency department satellite laboratory by hospital staff. Test results were analyzed by correlation to the clinical discharge diagnosis. RESULTS: In the emergency department, for the test system as a whole (any one or more marker(s) positive versus all three markers negative), sensitivity was 63%, specificity was 81%, positive predictive value was 26%, and negative predictive value was 95%. A manufacturer-supplied product specialist in a laboratory setting achieved very similar sensitivity, specificity, and positive and negative predictive values. CONCLUSIONS: The performance of this system under controlled laboratory conditions can be applied to estimate its performance at the point of care.

Adult↗

The laboratory and the general practitioner.

Clinical laboratories provide vital services for primary care and such work will inevitably increase with the moves to increase the extent to which patients are treated in the primary care setting, an increase in day-case surgery and shorter in-patient stay. The relationship between clinical laboratories and general practitioners should be a partnership with both the parties communicating efficiently in the interest of the patient. In particular, a close relationship between general practitioners and specialists in laboratory medicine is mandatory for handling the increasing number and complexity of laboratory tests, assuring the appropriateness of their request and utilization. In addition, the enormous increase in near-patient testing procedures claims for joint efforts to assure the quality of laboratory results. The General Practitioner always has the responsibility to understand the relevance of a test result and, where appropriate, to investigate further or to refer, irrespective of where the test has been done, but laboratory consultation can assure a better utilization of laboratory services for improving patient outcomes.

Family Practice↗

A study to examine the accuracy of potassium measurements in clinical laboratories across Canada.

OBJECTIVE: To assess the accuracy of potassium measurements in clinical laboratories across Canada. DESIGN AND METHOD: The flame atomic emission spectrophotometry reference method for the determination of potassium was established at the Canadian Reference Laboratory by using National Institute of Science and Technology standard reference materials. The method was subsequently used to assign target values for potassium to Canadian Reference Laboratory's External Quality Assessment human-serum-based testing material. A total of 503 laboratories participated and 9,279 individual External Quality Assessment test results were included in the study. Bias was determined by using difference plots. RESULTS: Clinically significant bias (>1.6%) was observed in 45.9% of the laboratories. Bias ranged from 0.34 mmol/L to -0.54 mmol/L. At low concentrations (<3.5 mmol/L) a positive bias was most frequently observed (14.7% of analytical systems). At high potassium concentrations (>5.1 mmol/L) a negative bias was most frequently observed (31.4% of analytical systems). CONCLUSION: Inaccuracy in potassium results can contribute to test redundancy and mismanagement of patients, while prohibiting the merger of laboratory data from disparate testing sites for the purpose of trending and consolidation within a "universal health record." Inaccurate test results and the lack of standardization among laboratories adversely impact our ability to establish common reference intervals and critical limits. This inability has an adverse effect on medical decisions and patient care.

Bias↗