Falsely normal anion gap in severe salicylate poisoning caused by laboratory interference.

Severe salicylate poisoning is classically associated with an anion gap metabolic acidosis. However, high serum salicylate levels can cause false increase of laboratory chloride results on some analyzers. We present 2 cases of life-threatening salicylate poisoning with an apparently normal anion gap caused by an important laboratory interference. These cases highlight that the diagnosis of severe salicylism must be considered in all patients presenting with metabolic acidosis, even in the absence of an increased anion gap.

Intra-individual variation in serum C-reactive protein over 4 years: an implication for epidemiologic studies.

BACKGROUND: Data on long-term intra-individual variability in high-sensitivity C-reactive protein (hsCRP) are needed to determine whether one measurement adequately reflects usual levels in prospective studies of on the etiology of cancer and other chronic diseases; when not reflective, the ability to statistically detect modest to moderate associations is reduced. The authors estimated the size of this source of variability and consequent attenuation of the relative risk (RR). METHODS: High-sensitivity C-reactive protein (hsCRP) concentration was measured using a high-sensitivity immunoturbidometric assay in sera collected at years 2, 4, and 6 from 50 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). After natural logarithm-transformation of hsCRP, analysis of variance was used to estimate the within- and between-individual variances from which the intra-class correlation coefficient (ICC) was calculated. RESULTS: The observed RR due to an ICC < 1 was calculated by e((ln true RR*ICC)) for a range of true RRs. The 4-year ICC was 0.66. Measuring hsCRP once and assuming no other error, if the true RRs were 1.50, 2.00, and 3.00 when comparing high with low concentration, then the observed RRs would be 1.31, 1.58, and 2.06, respectively. CONCLUSION: Investigators planning to measure hsCRP only once should design adequately sized studies to preserve inferences for hypothesized modest to moderate RRs.

The laboratory and patient safety.

Laboratory data are used extensively in patient care; consequently, laboratory errors have a tremendous impact on patient safety. Clinical laboratories were early leaders in efforts to minimize medical errors and improve patient safety. These efforts continue in many areas, including patient and specimen identification, laboratory result notification, and assistance in laboratory data interpretation. Emerging ideas on identifying and reducing laboratory errors, as well as specific strategies are reviewed and discussed with examples.

Laboratory testing in the intensive care unit.

Laboratory testing is ubiquitous among hospitalized patients and is more common among patients in the intensive care unit (ICU). Despite its high cost and prevalence, there are few data to support the current practice of laboratory testing in most ICUs. Although testing offers considerable potential benefits, it is not without risk, including misleading results, iatrogenic anemia, and therapeutic actions of uncertain benefit. Laboratory testing should be conducted as part of a therapeutic approach to a clinical problem, mindful of pretest probability of disease, the performance of the selected test, and the relative benefits and risks of testing. Considering the indication for a particular test can lead to a more rational approach to laboratory testing and better use of available tests.

[Laboratory diagnosis: correlated health and environmental risks]. / La diagnostica di laboratorio: rischi sanitari e ambientali correlati.

Method description and initial results of a study to assess risks to health sector workers and environment due to chemical agents used and waste products generated in diagnostic clinical chemical laboratories, and image diagnostic testing. A survey was conducted of the methods and agents used and their toxicological classification, the number of workers exposed and an analytical profile of the waste produced. The assessment of risk to workers was based on cytogenetic tests (chromosome aberrations and micronuclei); the assessment of environmental risk from waste disposal was based on tests on plant systems.

Physiological changes in membrane-expressed platelet factor 4: implications in heparin-induced thrombocytopenia.

BACKGROUND: Many heparin-induced thrombocytopenia (HIT) antibodies cause platelet activation in the serotonin release assay (SRA) in the absence of heparin. This in vitro observation may help unravel the mechanism of delayed-onset HIT, where seropositive patients develop thrombocytopenia and associated thrombosis after cessation of heparin. OBJECTIVE: Studies were conducted to examine the relationship between platelet environment, surface PF4 expression, and the extent of heparin-independent platelet activation in the SRA. METHODS: Ex vivo platelets were washed and labeled for SRA, then used either before or after 45 minutes of recovery at 37 degrees C. HIT antibody-mediated serotonin release in the absence of heparin was compared to the extent of surface staining of the platelets with fluorescent anti-human PF4 antibodies. RESULTS: Handling of platelets for in vitro studies resulted in transient expression of surface PF4, and it was during this interval that platelets were most sensitive to activation by HIT antibodies in the absence of heparin. Heparin-independent platelet activation was attenuated when SRA-positive specimens were retested after platelets were incubated 45 minutes at 37 degrees C. Surface PF4 expression was diminished on the rested platelets, compared to the same platelets labeled immediately after handling. Thus compared to rested platelets, mildly activated platelets had elevated surface PF4 expression and a higher level of HIT antibody-mediated, heparin-independent platelet activation. CONCLUSION: Surface expression of PF4 reflects HIT antigen presentation, and varies with the physiological state of platelets. Thus there can be differences in HIT antibody target availability among patients which may explain the variability in consequences of HIT antibody seropositivity.

How can we make laboratory testing safer?

BACKGROUND: Diagnostic errors occur in laboratory medicine resulting from an error or delay in diagnosis, a failure to employ indicated tests, and the use of outmoded tests. Since laboratory tests provide essential information used by physicians to make medical decisions, it is important to determine how often laboratory testing mistakes occur, whether they cause patient harm, where they are most likely to occur in the testing process, and how to prevent them from occurring. METHODS: The US Quality Institute Conference in 2003 and the Institute for Quality in Laboratory Medicine in 2005 brought together providers of, users of, and payers for laboratory services to explore how working together they could help to reduce laboratory testing errors and enhance patient safety. RESULTS AND CONCLUSIONS: Users of and payers for laboratory services must become partners in the laboratory's efforts to reduce laboratory testing errors and enhance patient safety. They must be linked to a laboratory information system that provides assistance in decisions on test ordering, patient preparation, and test interpretation. Laboratory quality assessment efforts need to be expanded to encompass the detection of non-analytical mistakes. Healthcare institutions need to adopt a culture of safety that is implemented at all levels of the organization.

Automating identification of adverse events related to abnormal lab results using standard vocabularies.

Laboratory data need to be imported automatically into central Clinical Study Data Management Systems (CSDMSs), and abnormal laboratory data need to be linked to clinically related adverse events. This import of laboratory data can be automated through mapping to standard vocabularies with HL7/LOINC mapping to the metadata within a CSDMS. We have designed a system that uses the UMLS metathesaurus as a common source to map or link abnormal laboratory values to adverse event CTCAE coded terms and grades in the metadata of TrialDB, a generic CSDMS.

False-positive results and contamination in nucleic acid amplification assays: suggestions for a prevent and destroy strategy.

Contamination of samples with DNA is still a major problem in microbiology laboratories, despite the wide acceptance of PCR and other amplification techniques for the detection of frequently low amounts of target DNA. This review focuses on the implications of contamination in the diagnosis and research of infectious diseases, possible sources of contaminants, strategies for prevention and destruction, and quality control. Contamination of samples in diagnostic PCR can have far-reaching consequences for patients, as illustrated by several examples in this review. Furthermore, it appears that the (sometimes very unexpected) sources of contaminants are diverse (including water, reagents, disposables, sample carry over, and amplicon), and contaminants can also be introduced by unrelated activities in neighboring laboratories. Therefore, lack of communication between researchers using the same laboratory space can be considered a risk factor. Only a very limited number of multicenter quality control studies have been published so far, but these showed false-positive rates of 9-57%. The overall conclusion is that although nucleic acid amplification assays are basically useful both in research and in the clinic, their accuracy depends on awareness of risk factors and the proper use of procedures for the prevention of nucleic acid contamination. The discussion of prevention and destruction strategies included in this review may serve as a guide to help improve laboratory practices and reduce the number of false-positive amplification results.

Trusting numbers: uncertainty and the pathology laboratory.

Diagnostic laboratories are increasingly seen as no more than "factories" that generate fast, reliable test results. The dangers of complacency about the use of tests are highlighted by recent cases of unnecessary surgery and chemotherapy based solely on false-positive test results. There are many causes of misleading laboratory data that can potentially lead to clinical mismanagement. Re-emphasis of the value of patient-relevant communication between the requesting doctor and the laboratory, and better undergraduate and postgraduate education about the appropriate use of tests, will help reduce the risks of test results leading to harm.

Adolescents with atopic disorders have an attenuated cortisol response to laboratory stress.

BACKGROUND: Patients with allergic disorders have been noted to have variations in cortisol patterns under natural conditions as well as a differential cortisol response to stress. OBJECTIVE: The main goal of this study was to examine hypothalamic-pituitary-adrenal (HPA) axis differences in atopic adolescents. METHODS: Subjects were a community sample of 202 adolescents (52% male; mean age, 16.2 years). Atopic status was determined by skin testing and clinical history. Saliva samples for cortisol assay were obtained 4 times during a "typical day" and at 4 time points during laboratory procedures. RESULTS: One third of the sample (33%) had a clinical atopic disorder, primarily allergic rhinitis; 39% had positive skin test results without clinical symptoms; and 27% had no signs or symptoms of allergic disorders. There were no significant effects of atopic status on home cortisol patterns. Presence of clinical atopy was significantly (P <.05) associated with lower cortisol levels in response to laboratory stressors. CONCLUSIONS: Adolescents with a history of atopic illnesses had an attenuated cortisol response to the stress of laboratory procedures compared with adolescents with positive skin test results alone or nonatopic adolescents. An attenuated cortisol response to a stressor may help us understand the link between stress and exacerbation of atopic illness.

Métodos laboratoriais disponíveis para o diagnóstico da filariose linfática / Available laboratorial diagnostic methods of the lymphatic filariasis

O presente trabalho tem como objetivo revisar os métodos laboratoriais disponíveis para se diagnosticar a filariose linfática bancroftiana. Doença transmitida pelo vetor Culex quinquesfasciatus, e que é encontrada no Brasil, na Regiäo Metropolitana de Recife - PE, Maceió - AL, e Belém - PA. Apesar de existir uma variedade de testes utilizando a pesquisa do parasito, anticorpo, antígeno e DNA, na rotina diagnóstica, um cuidado deve ser tomado pelo profissional de saúde na interpretaçäo dos resultados, quer para diagnóstico ou descarte de infecçäo filarial, quer principalmente para atribuir ou näo à filariose, um quadro de adenopatia, linfedema ou hidrocele de que o paciente seja portador