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A model for harmonization of routine clinical chemistry results between clinical laboratories.

Clinical chemistry laboratory results from different laboratories often show large between-laboratory variation due to factors such as differences in method principles, method applications, calibration procedures or the application of different instrument factor settings within the same calibration procedure. We have examined the possible use of common calibrators to reduce this variation. Three different calibrators were compared: A, freeze-dried preparations of pooled patients' serum samples, spiked to give three concentration levels; B, freeze-dried preparations of pooled patients' serum samples selected on the basis of elevated enzyme activities at three levels; C, a single calibrator consisting of frozen pooled serum samples. These calibrators were sent to 11 participating laboratories together with 14 fresh patients' serum samples. We report the variation of the results of 21 general clinical chemistry analytes obtained in the patients' serum samples before and after recalculation on the basis of the results of the calibrators. For most analytes the use of a multiple point linear regression calibration function is able to reduce the between-laboratory variation considerably from more than 30% (enzymes) to values well within the bias limits set by European quality specifications, when the necessary conditions are met. These conditions include the commutability of the calibrator(s) with fresh patients' material. For the enzymes, calibrator material originating from selectively pooled patients' samples appeared to be necessary, whereas for the substrates selectively pooled serum calibrators spiked with exogenous supplements may be used. For harmonization to be effective in practice, calibrators need to be stable over time and to carry assigned values set by certified reference laboratories, and the quality performance of participating laboratories should be appropriately monitored.

Calibration↗

Laboratory diagnosis of von Willebrand disorder. Current practice in the southern hemisphere.

A survey of 44 laboratories was conducted to evaluate current testing proficiency in the diagnosis of von Willebrand disorder (vWD) and to assess recent changes in test practices. Laboratories performed their usual panel of tests for vWD and interpreted results for the likelihood of vWD and potential subtype. Samples were as follows: normal plasma; borderline normal or abnormal levels of von Willebrand factor (vWF) and factor VIII; type 3 vWD; type 2A vWD; and 2 samples from a healthy person, processed after handling at 22 degrees C and 4 degrees C, respectively. Interassay and within-method coefficients of variation were similar for all assays (approximately 15%-25%). Most laboratories reported test values consistent with expected findings and made correct interpretations, although discrepant results for 5% to 10% of responses are of concern. For the sample stored at 4 degrees C, all laboratories detected low or borderline levels of vWF and factor VIII coagulant, and no laboratory identified this sample as from a healthy person. In contrast, for the sample stored at 22 degrees C, most laboratories reported normal results. Compared with previous results, performance of some assays has declined while that of others has increased. Laboratories generally are proficient in tests for vWD, and transport of samples at 4 degrees C before processing may lead to false identification of vWD, suggesting that NCCLS guidelines should be reviewed.

Antigens↗

How often do GPs use rapid computer access to laboratory results? A description of 18 months' use by 72 practices in Tayside.

This paper describes the uptake and usage by a group of general medical practices in Tayside, Scotland of a novel system designed to give rapid access to laboratory results in primary care. The speed of access to laboratory results from primary care is one factor that determines how laboratory results are both requested and used. Without easy and timely access to laboratory results, general practitioners (GPs) are not able to make the most efficient use of laboratory tests, and this therefore impinges on whether those tests are requested. Fountain was designed to provide a front end for GPs to gain rapid and easy access to laboratory results in a manner familiar to them. It was initially made available in primary care in the region to 72 practices, with 272 GP desktops having immediate access to results when they are ready. The pattern of use and uptake was monitored remotely after the system was introduced, and the first 18 months of use are described here. Initial use varied widely between practices with rates of access varying from 160 hits per 1000 population to none at all. However, the access rate gradually conformed to a more standard rate of around 20 hits per 1000 population per month, regardless of the initial rate of use. This pattern conforms to that describing the introduction of new technologies in other settings. Continued use in practice and the concordance of usage between practices confirms that rapid and reliable access to laboratory reports from primary care is both useful and used.

Clinical Laboratory Information Systems↗

The origin of clinical laboratories.

Clinical laboratories are a main attribute of clinical chemistry. Their historical development is therefore of great interest in the history of clinical chemistry. The results of a study are given which was undertaken to trace the establishment of clinical laboratories in central Europe, mainly in France, England and in the German-speaking countries. Presuppositions for the creation of these laboratories were: (i) The idea that the results of laboratory examinations can be used as "chemical signs" in medical diagnosis, and (ii) a new concept of disease which was the result of the "birth of the clinic" at the end of the 18th century. The study shows that the development of clinical laboratories began 200 years ago. Up to the end of the 19th century, three development phases can be distinguished: an early phase from 1790 to 1840, a phase of institutionalization from 1840 to 1855, and a phase of extension between 1855 and 1890. To characterize these three phases, the foundation of the laboratories, the layout of the laboratory rooms, their equipment and instrumentation, and the usual staff are described with the aid of typical examples.

Chemistry, Clinical↗

[Parity of Ochlerotatus scapularis in laboratory and field conditions].

OBJECTIVE: To identify the parity status of Ochlerotatus scapularis females in laboratory and field conditions. METHODS: Field collections were carried out fortnightly using a hand-held aspirator in Vale do Ribeira, Southeastern Brazil, from April 2003 to March 2004. In laboratory, 100 Ochlerotatus scapularis F1 females were obtained and followed up individually, reporting the number of blood meals, the length of gonotrophic cycle, survival and number of eggs laid. The parity status and ovarian development were observed through ovarian dissection of 90 field females for each collection and all females reared in laboratory. RESULTS: The parity status diagnoses of the 100 females reared in laboratory and dissected agreed with 55% of the oviposition data, and it was underestimated in 37% and overestimated in 2%. Also in the laboratory, 106 gonotrophic cycles were completed, around 55% of females needed more than one blood meal before laying eggs. In laboratory conditions the species survival was 26 days. A total of 1,180 field females of Ochlerotatus scapularis were dissected: 418 (35.4%) nulliparous, 655 (55.5%) uniparous, 46 (3.9%) biparous and 61 (5.2%) could not be evaluated. Ninety field females were found in Christophers and Mer's phase III-V. CONCLUSIONS: The gonotrophic discordance hypothesis could be confirmed based on field and laboratory observations of Ochlerotarus scapularis females.

Animals↗

A meta-analysis comparing the toxicity of sediments in the laboratory and in situ.

Sediment toxicity tests in the laboratory are an important part of ecological risk assessments, yet how they relate to sediment toxicity in situ has rarely been explored. Using meta-analysis, we examined differences in the toxicity of sediment tested in the laboratory and in situ. Data from four published studies were subjected to rigorous statistical analyses. Overall, the toxicity of sediments in laboratory tests was substantially less than their toxicity in situ. Differences between laboratory and in situ toxicity, expressed using the log odds ratio effect size, varied significantly among published studies. Effect size increased significantly with increasing sediment toxicity, showing that the more toxic the sediment, the greater the disparity between laboratory and field toxicities. Our findings may not apply to all laboratory/field comparisons; however, we consider that the overlying water in field situations is a significant contributor to this relationship through additional contamination and toxicity. Our findings also have important implications for the use of laboratory tests to assess improvements in sediment quality and remediation, because changes in laboratory toxicity may not reflect the true improvements to sediment quality in situ.

Geologic Sediments↗

Transferability of clinical laboratory data within a health care region.

Analytical data for S-Creatinine and S-Urate are presented from seventeen laboratories in the Swedish Uppsala-Orebro regional quality assessment program. The bias and imprecision as well as the instability of the measurement procedures in the participating laboratories were estimated over three 14-week periods. Bias was estimated by a linear least squares fit of the difference between measured and assigned values vs. assigned values, and expressed in absolute and relative terms. Instability of the measurement procedures was estimated by comparing slope and intercept of regression lines of measured vs. assigned values from three fourteen week periods. According to our experiences we recommend regression analysis to describe the performance of the analytical methods of a laboratory over time. The results show that most laboratories fell within the limits of +/- 15% bias for S-Creatinine above 100 mumol l-1 and +/- 17% for S-Urate at concentrations above 250 mumol l-1. Various steps to reduce the inter-laboratory variability are suggested, including numerical correction of individual laboratory results using correction functions. In a few laboratories, instability was too high to allow for numerical corrections of analytical results.

Bias↗

Do out-of-office laboratory tests affect diagnoses in general practice?

OBJECTIVE: To find out whether the GP diagnosis changed by out-of-office laboratory test results and whether his diagnosis became more certain. DESIGN: Descriptive study. SETTING: Dutch survey of morbidity and interventions in general practice: stratified random sample of 161 GPs with a total list of 335,000 patients. SUBJECTS: 2,081 episodes of illness with at least one consultation with clinical chemistry, haematology, or serology tests and at least one follow-up consultation. MAIN OUTCOME MEASUREMENTS: Change in ICPC component or chapter between the consultation in which a laboratory test was ordered and the follow up contact; change in exact ICPC code in cases with important diseases (infectious diseases, haematological disorders, endocrine abnormalities, auto-immune processes and malignancies (n = 330)); change in certainty of a diagnosis and change in somatic/psychosocial orientation. RESULTS: After laboratory tests done in the first consultation the ICPC component changed in 46% of the diagnoses. Of the diagnoses made in first consultations without laboratory tests 41% changed in the follow up consultation. The diagnosis after laboratory tests was the same as before in 51% of the consultations with important diseases. Certainty about a diagnosis increased significantly after laboratory tests (p < 0.001). An abnormal laboratory result did not affect the clinical certainty of the general practitioner or the percentage of altered diagnoses. CONCLUSION: The usefulness of tests should be assessed not only in terms of the number of diagnoses changed or of the percentage of abnormal results, but also in terms of the changed certainty concerning a diagnosis.

Clinical Laboratory Techniques↗

Report of the Australian National Polio Reference Laboratory. 1 July to 31 December 1999.

Since 1994, as part of the global eradication of poliomyelitis, the Australian National Polio Reference Laboratory (NPRL) at the Victorian Infectious Diseases Reference Laboratory (VIDRL) has been responsible for virological testing to confirm the absence of poliomyelitis in Australia. Samples from patients with acute flaccid paralysis are transported to VIDRL for viral culture. Polio and enteroviruses are referred for intratypic differentiation as wild or Sabin (vaccine) strains. A total of 23 faecal specimens from 17 patients were processed for enterovirus culture in the period 1 July to 31 December 1999. Since 1995, 1,078 enterovirus isolates from six states have been tested for the presence of wild poliovirus. To date, 562 strains were confirmed as Sabin vaccine-like, one non Sabin-like strain was identical with a laboratory control virus and the other strains were non-polio enteroviruses or other viruses. A World Health Organization (WHO) workshop in diagnostic polio polymerase chain reaction techniques was held at VIDRL in November 1999. The laboratory was reaccredited as a regional polio reference laboratory for the WHO Western Pacific region and a national laboratory for Australia, the Pacific Island countries and Brunei Darussalam. Planning is proceeding for the polio-free certification and containment of laboratory stocks of wild poliovirus infectious materials in Australia.

Australia↗

Annual report of the Australian National Poliovirus Reference Laboratory, 2004.

The Australian National Poliovirus Reference Laboratory at the Victorian Infectious Diseases Reference Laboratory is the World Health Organization designated laboratory for the isolation and testing of poliovirus from clinical specimens within Australia, the Pacific Island countries and Brunei Darussalam. Surveillance for acute flaccid paralysis (AFP) within Australia, the main clinical manifestation of poliomyelitis, is also coordinated at the Victorian Infectious Diseases Reference Laboratory in conjunction with the Australian Paediatric Surveillance Unit. The annual non-polio acute flaccid paralysis rate after classification of cases by the Polio Expert Committee was 1.0 per 100,000 population, reaching the expected World Health Organization annual target for a non-polio endemic country. During 2004, 64 specimens from 30 AFP cases were referred to the National Polio Reference Laboratory. A mixture of poliovirus types 1 and 2 was isolated from an infant with AFP from New South Wales. Both isolates tested as Sabin-like and the case was subsequently classified as infant botulism by the Polio Expert Committee. The laboratory isolated adenoviruses from seven AFP cases. A coxsackievirus B5 and an echovirus 18 were identified from a further two AFP cases. During 2004, 1,266 cases of poliomyelitis due to wild poliovirus were reported world-wide. Many of these resulted from wild poliovirus importations, which continued in 2005, including to Indonesia. This highlights the need for maintaining high poliovirus vaccination coverage to prevent the transmission of poliovirus and high quality AFPand laboratory surveillance for the detection of poliomyelitis due to an imported wild poliovirus.

Adolescent↗

Adverse reproduction outcomes among employees working in biomedical research laboratories.

OBJECTIVES: The aim of the study was to investigate reproductive outcomes such as birthweight, preterm births, and postterrm births among women working in research laboratories while pregnant. METHODS: Female university personnel were identified from a source cohort of Swedish laboratory employees, and the database was linked to the medical birth register. The first births of the women were included in the analysis, 249 pregnancies among the women with laboratory work and 613 pregnancies among the women without laboratory tasks. Information about exposure to various laboratory agents was obtained from a previous questionnaire investigation at the research group level according to a specific definition. The ponderal index and ratio between observed and expected birthweights were calculated. Logistic regression models were used for analyses of dichotomous outcomes (preterm, postterrm and birthweight). RESULTS: Exposure to laboratory work with solvents was associated with an increased risk of preterm births, the estimated odds ratio (OR) being 3.4 (1.0 < 95% confidence interval < 11.9). An association with work with bacteria was also observed for postterm births (OR 2.7, 1.0 < or = 95% confidence interval < 7.4). CONCLUSIONS: There was a slightly elevated risk for some reproductive outcomes among the women working with certain laboratory tasks, specifically for preterm and postterm births in relation to work with solvents and bacteria.

Birth Weight↗

Health Care Financing Administration/clinical laboratory improvement amendments of 1988.

The Health Care Financing Administration has introduced new concepts for the Clinical Laboratory Improvement Amendments of 1988 survey program. Surveyors now look at the laboratory as a whole as opposed to each regulatory requirement independently. This quality assurance approach allows the surveyor to assess the laboratory's ability to provide quality test results as well as identify and correct its own problems. Significant problems in laboratories are more easily identified using this method. Another new concept allows good performing laboratories to go longer between on-site surveys by completing a self-assessment questionnaire on alternate cycles. The Health Care Financing Administration is asking both surveyors and laboratories to evaluate these new approaches. The Health Care Financing Administration continues to work with the Food and Drug Administration through our Memorandum of Understanding to assess Food and Drug Administration requirements in hospitals and laboratories that provide transfusion services. Transfusion-related fatalities must be reported to the Food and Drug Administration and may be investigated by either the Health Care Financing Administration or the Food and Drug Administration. For fatalities needing investigation by both agencies, every effort will be made to conduct these jointly.

Accreditation↗

Quality control of test systems waived by the Clinical Laboratory Improvement Amendments of 1988. Perceptions and practices.

CONTEXT: Recent advances in laboratory testing technology have resulted in a rapidly increasing number of test systems targeted for physician office, point-of-care, and home health care settings. With enhanced error detection mechanisms and unitized reagents, these new systems simplify the testing process and the assessment of analytical test performance. Many also meet the criteria set by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to qualify as waived test systems, and laboratories using only waived tests are subject to very limited regulatory oversight. OBJECTIVE: To evaluate use patterns and perceptions about quality control requirements with respect to waived testing. DESIGN AND SETTING: Survey of a network of 431 hospital, independent, and physician office laboratories in the US Pacific Northwest. RESULTS: Responding laboratories (n = 221) were taking advantage of the availability of waived tests and using them to make definitive diagnoses. We found considerable differences between quality control practices and the laboratories' perceptions of quality control requirements. Most respondents were performing traditional quality control on waived tests, influenced by their interpretation of regulations, the intended use of the test, and the testing personnel employed. CONCLUSIONS: Technology optimized for alternate quality control can represent an improvement in ease of use while meeting expectations for accuracy and providing relief from regulatory burdens. However, laboratory personnel exhibit confusion in applying new quality control systems.

Attitude of Health Personnel↗

Nongynecologic cytology turnaround time: a College of American Pathologists Q-Probes study of 180 laboratories.

OBJECTIVES: To determine the turnaround time for nongynecologic cytology and to identify laboratory and specimen characteristics associated with variations in turnaround time. DESIGN AND SETTING: Prospective evaluation of nongynecologic cytology turnaround times in 180 laboratories. MAIN OUTCOME MEASURE: Nongynecologic cytology case turnaround time. RESULTS: Participants from 180 laboratories submitted turnaround times for 16 950 nongynecologic cytology cases and submitted information describing their laboratories' practice characteristics relating to the processing of nongynecologic cytology specimens. Half of the participating laboratories had mean receipt to report turnaround times of 1.6 calendar days or less and were able to complete 90% of their cases within 3.0 calendar days. Ten percent of participants had mean turnaround times greater than 3.2 days and required 6.0 or more days to report 90% of their cases. Longer turnaround times were associated with processing fluid and fine-needle aspiration specimens, issuing atypical/suspicious for malignancy and nondiagnostic diagnoses, having cytotechnologist students screen slides, having to contact the physician offices for additional information, having to retrieve prior case material for review, and having to perform cell blocks and/or special stains. CONCLUSION: There is an opportunity for laboratories to shorten nongynecologic turnaround time by altering certain laboratory practices.

Biopsy, Needle↗

Six-year trends in laboratory computer availability.

CONTEXT: Failure of a clinical laboratory computer system can disrupt work flow and charge capture and affect patient care. The first comprehensive survey of computer downtime was conducted in 1995 and demonstrated significant interinstitutional variation in system availability. Despite numerous changes in the laboratory and computer industries since 1995, no follow-up study has been reported. OBJECTIVES: To quantify current laboratory computer availability and compare it with 1995 performance. DESIGN: Ninety-seven laboratories prospectively recorded the frequency and duration of computer downtime during 30 days in 2001. Results were compared with 1995 survey data. RESULTS: For the median facility, the number of downtime episodes decreased from 8 events per 30 days during 1995 to 3 events per 30 days during 2001 (P <.01). The frequency of unscheduled downtime also improved, from a median of 2 to 0.5 events per 30 days (P <.01). Reduced downtime events were paralleled by reduced cumulative downtime (14.3 vs 4.0 hours per 30 days; P <.01). Improvements were not restricted to the median facility; laboratories performing in the bottom quartile in 2001 recorded substantially less downtime than laboratories in the bottom quartile in 1995. When the comparison was restricted to the 37 institutions that participated in both the 1995 and 2001 surveys, a significant reduction in overall downtime and unscheduled downtime events was still evident (P <.01). More recent installation of vendor software patches was associated with a reduced frequency of downtime events in the 2001 data set. CONCLUSION: Laboratory computer downtime was less frequent in 2001 than in 1995; industry performance appears to be improving.

Clinical Laboratory Information Systems↗

Age and laboratory costs for hospitalized medical patients.

OBJECTIVE: To examine the hypothesis that older hospitalized patients have higher laboratory costs than younger patients in the same severity-adjusted diagnosis-related group (DRG). DESIGN: We obtained hospital case mix data sets (1995-1997) from the Massachusetts Division of Health Care Finance and Policy. We selected discharge abstracts from 4 medical DRGs, at 5 large academic hospitals (n = 15,265) and 5 midsized community hospitals (n = 10,540), for analysis. We converted laboratory and blood product charges to direct costs using the department-specific ratio of cost to charges. We adjusted diagnostic groups for severity of comorbid conditions and complications using the refined DRG method. MAIN OUTCOME MEASURES: Hospital length of stay (LOS), laboratory direct cost (LDC) per hospitalization, LDC per hospital day, and ratio of LDC to total direct cost. RESULTS: Hospital LOS was longer for older patients in all comparisons. Laboratory direct cost per hospitalization was higher for older patients in some DRGs, but lower in other DRGs. Laboratory direct cost per hospital day was almost always less for older patients than for younger patients, both at academic and community hospitals. Data stratification by gender, admission status, and principal diagnosis yielded substantially the same pattern of cost differences observed within the larger data set. CONCLUSIONS: Older medical patients have longer hospital stays and generally higher costs. These patients also have a significantly decreased rate of laboratory resource consumption over the course of hospitalization (LDC per hospital day), as well as lower laboratory costs as a proportion of total costs. Age-specific differences in LOS and cost parameters were essentially unchanged after controlling for several potential sources of bias.

Adolescent↗

The variability of results between point-of-care testing glucose meters and the central laboratory analyzer.

CONTEXT: Point-of-care testing glucose meters are strongly recommended in the management of diabetes and are increasingly being used for making therapeutically important decisions. Thus, it is essential that their results correlate well with those of laboratory analyzers. OBJECTIVES: To test the reliability of point-of-care testing glucose meters. DESIGN: Two studies were performed: (1), an in-house study comparing accuracy of point-of-care testing glucose meters with a reference analyzer using fresh whole blood specimens (2), a real-time comparison of (a) 2 successive glucose meter readings and (b) glucose meter reading to central laboratory analyzer reading. SETTING: (1), Seven glucose meters from 4 manufacturers were compared with the Yellow Springs YSI 2300 blood glucose analyzer using whole blood without preservative. (2), (a) Whole blood samples were read within 5 minutes of each other using Accu-Chek meters and (b) between a glucose meter and a Hitachi laboratory analyzer. RESULTS: (1) Within the Accu-Chek group of glucose meters, fresh, preservative-free whole blood samples showed the lowest bias. (2) At the hypoglycemic level, successive glucose meter readings agreed well, but there was considerable disagreement between glucose meter and central laboratory values. Because laboratory analyzers are of proven accuracy, they are used as the reference. In the glucose meter-central laboratory analyzer correlation, for both hypoglycemic and hyperglycemic values, readings in which the differences were greater than 10% occurred more than 61% of the time. In the hypoglycemic range, differences greater than 20% occurred 57% of the time. CONCLUSIONS: One should scrutinize point-of-care testing glucose meter readings at the hypoglycemic and hyperglycemic levels and whenever possible to corroborate these clinical results with central laboratory analyzers.

Blood Chemical Analysis↗

Herbal remedies: effects on clinical laboratory tests.

CONTEXT: Complementary and alternative medicine (herbal medicines) can affect laboratory test results by several mechanisms. OBJECTIVE: In this review, published reports on effects of herbal remedies on abnormal laboratory test results are summarized and commented on. DATA SOURCES: All published reports between 1980 and 2005 with the key words herbal remedies or alternative medicine and clinical laboratory test, clinical chemistry test, or drug-herb interaction were searched through Medline. The authors' own publications were also included. Important results were then synthesized. DATA SYNTHESIS: Falsely elevated or falsely lowered digoxin levels may be encountered in a patient taking digoxin and the Chinese medicine Chan Su or Dan Shen, owing to direct interference of a component of Chinese medicine with the antibody used in an immunoassay. St John's wort, a popular herbal antidepressant, increases clearance of many drugs, and abnormally low cyclosporine, digoxin, theophylline, or protease inhibitor concentrations may be observed in a patient taking any of these drugs in combination with St John's wort. Abnormal laboratory results may also be encountered owing to altered pathophysiology. Kava-kava, chaparral, and germander cause liver toxicity, and elevated alanine aminotransferase, aspartate aminotransferase, and bilirubin concentrations may be observed in a healthy individual taking such herbal products. An herbal product may be contaminated with a Western drug, and an unexpected drug level (such as phenytoin in a patient who never took phenytoin but took a Chinese herb) may confuse the laboratory staff and the clinician. CONCLUSIONS: Use of alternative medicines may significantly alter laboratory results, and communication among pathologists, clinical laboratory scientists, and physicians providing care to the patient is important in interpreting these results.

Clinical Laboratory Techniques↗