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Biomedical subjects

W P Oosterhuis

Publications and source records attributed to W P Oosterhuis.

At least 19 recordsLinked to original sources

Diagnostic value of the mean corpuscular volume in the detection of vitamin B12 deficiency.

In clinical practice, the finding of an elevated mean corpuscular volume (MCV), macrocytic anaemia or specific neurological symptoms is often the reason to test for vitamin B12 (B12) deficiency. Use of the MCV as a test for the detection or exclusion of B12 deficiency is only justified if the diagnostic accuracy is sufficiently high. However, the sensitivity and specificity are not well known. We performed a systematic review of the diagnostic value of an elevated MCV for B12 deficiency in both anaemic and non-anaemic patients. Of approximately 3500 titles and/or abstracts that were screened, 37 original papers contained usable data. The population under study proved to be the characteristic of major influence on the study outcome. Pooling of data from different studies was performed in subsets of the data corresponding to the different populations studied. The cut-off levels of both MCV and serum B12 had a significant influence on the study outcomes. The data, however, were pooled without taking these cut-off levels into account. The pooled estimates should be interpreted with this limitation in mind. The reference standards were (1) a low serum B12 concentration and (2) a B12 deficiency confirmed by low serum B12 combined with additional diagnostic investigations. In the population that was randomly screened for low serum B12, the sensitivity of the MCV for B12 deficiency was 17%, whereas the sensitivity was 30% for B12 deficiency in patients with anaemia. When measurement of serum B12 was ordered to exclude B12 deficiency as part of the patients' treatment, the sensitivity was 30% for low serum B12 concentration, 58% for B12 deficiency and 75% for B12 deficiency in patients with anaemia. In the population with pernicious anaemia, the sensitivity was far from perfect (77%). In the five studies that reported data on the positive predictive value of the MCV for B12 deficiency, this ranged from 0% (0/6) to 55% (11/20). This systematic review shows that a considerable number of B12-deficient patients will remain unnoticed when the MCV is used to rule in patients for further evaluation. Depending on the population studied, up to 84% of cases will than be missed. The MCV can be used to make the diagnosis of B12 deficiency more--or less--probable. An elevated MCV justifies the measurement of serum B12. The MCV should not be used as the only parameter ruling out the diagnosis of B12 deficiency.

Erythrocyte Indices↗

The science of systematic reviewing studies of diagnostic tests.

BACKGROUND: Systematic reviews have gradually replaced single studies as the highest level of documented effectiveness of health care interventions. Systematic reviewing is a new scientific method, concerned with the development and application of methods for identifying relevant literature, analysing the material while increasing validity and precision, and presenting and discussing the results in a way that does justice to the research question and to the available evidence. The objective of this study was to review the systematic reviews in laboratory medicine, to evaluate the methods applied in these reviews and the applicability of guidelines of the Cochrane Methods Working Group on Screening and Diagnostic Tests, and identify areas for future research. METHODS: All the systematic reviews in the field of clinical chemistry and laboratory haematology that could be identified in Medline, EMBASE and other literature databases up to December 1998, were evaluated. RESULTS: We studied 23 reviews of diagnostic trials. Although all reviews share the same basic methodology, there was a wide variation in the methods applied. There was no consensus on the quality criteria for inclusion of primary studies. The results of the primary studies were heterogeneous in most cases. This was partly due to design flaws in the primary studies, but was also inherent in the diverse study designs in diagnostic trials. We observed differences in the analysis of the factors that cause heterogeneity of the results, and in the summary statistics used to pool the data from the primary studies. The additional diagnostic value of a test, after other test results are taken into consideration, was only addressed in one study. CONCLUSION: This overview of 23 reviews of diagnostic trials identifies areas in the methods of systematic reviewing where consensus is lacking, such as quality rating of primary studies, analysis of heterogeneity between primary studies and pooling of data. Guidelines need to be improved on these points.

Clinical Chemistry Tests↗

Evaluation of LabRespond, a new automated validation system for clinical laboratory test results.

BACKGROUND: Manual validation of laboratory test results is time-consuming, creating a demand for expert systems to automate this process. We have started to set up the program "LabRespond", which covers five validation levels: administrative, technical, sample, patient, and clinical validation. We present the evaluation of a prototype of an automated patient validation system based on statistical methods, in contrast to the commercially available program "VALAB", a rule-based automated validation system. METHODS: In the present study, 163 willfully altered, erroneous test results out of 5421 were submitted for validation to LabRespond, VALAB, and to a group of clinical chemists (n = 9) who validated these test results manually. The test results rejected by three or more clinical chemists (n = 281) served as a secondary reference standard. RESULTS: The error recovery rates of clinical chemists ranged from 23.9% to 71.2%. The recovery rates of LabRespond and VALAB were 77.9% and 71.8%, respectively (difference not significant). The false-positive rates were 82.7% for LabRespond, 83.6% for VALAB, and 27.8-86.7% for clinical chemists. Using the consensus of three or more clinical chemists as the secondary reference standard, we found error recovery rates of 64.8% for LabRespond and 72.2% for VALAB (P = 0.06). Compared with VALAB, LabRespond detected more (P = 0.003) erroneous test results of the type that were changed from abnormal to normal. CONCLUSIONS: The statistical plausibility check used by LabRespond offers a promising automated validation method with a higher error recovery rate than the clinical chemists participating in this study, and a performance comparable to VALAB.

Clinical Laboratory Techniques↗

Reflex sympathetic dystrophy: is the immune system involved?

OBJECTIVE: Evaluation of immune system function in patients with reflex sympathetic dystrophy (RSD). DESIGN: Survey on blood samples obtained from RSD patients and from a randomly selected control group. The lymphocyte populations (T, B, NK cells), and the activated T cells (CD25, and HLA-Dr-positive CD4 and CD8 cells) were analyzed by flow cytometry with dual-color direct immunofluorescence after whole-blood lysis. Clinical chemistry parameters were analyzed in additional serum samples. SETTING: Tertiary care center (outpatient rehabilitation clinic). SUBJECTS: Thirteen patients (nine women) with RSD and a control group of 21 healthy individuals. MAIN OUTCOME MEASURES: The results of the flow cytometry analysis of RSD patients were related to those of the control subjects. Means were analyzed, and confidence intervals for differences of the means were calculated. The means of the clinical chemical analysis were related to local reference values. RESULTS: The flow cytometry analysis did not differ between RSD patients and healthy controls. Although in some patients an individual parameter of clinical chemical analysis differed from its reference value, all of the mean values were within reference limits. Stratification on medications with immunomodulatory effects and on probability of a definite diagnosis of RSD had no influence on the results. CONCLUSION: No association between immunologic indices and RSD was found. This finding is relevant, because recent theories stress that it is not the sympathetic nervous system but a local inflammatory reaction that is fundamental in the pathogenesis of RSD. The results of this study do not support this theory.

Adult↗

Patients with a normal exercise thallium-201 myocardial scintigram: always a good prognosis?

The prognostic value of a normal exercise thallium-201 scintigram was determined in 211 patients with a normal exercise and resting scintigram. Endpoints were sudden cardiac death, non-fatal acute myocardial infarction and coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. Forty patients (19%) had a history of a previous myocardial infarction and 40 (19%) were known to have had a previous percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. Sixty-four patients (31%) were on treatment with beta-blocking agents. After a mean follow-up period of 23.5 months, 22 patients had had a cardiac event (1 cardiac death, 6 myocardial infarction, 15 revascularization). For the total group, the 1-year event rate for cardiac death, myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass grafting was 7.0%. For cardiac death or myocardial infarction alone the event rate was 2.8%. The only parameter independently predictive for cardiac events was the regular use of beta-blocking agents. The high event rate in patients on beta-blocking treatment is partly due to the fact that these patients were more symptomatic for coronary artery disease. The sustained beta-adrenergic blockade in this patient group, even in patients advised to stop medication, was suspected to interfere with the results of 201Tl scintigraphy. Therefore, more attention should be paid to patient instruction regarding the discontinuation of medication before the test.

Adrenergic beta-Antagonists↗

C reactive protein in the diagnosis of acute appendicitis.

OBJECTIVE: To find out if the C reactive protein concentration is of any value in the diagnosis of acute appendicitis, either alone or in combination with other laboratory tests. DESIGN: Open study. SETTING: Drechtsteden Hospital, Dordrecht, and Spaarne Hospital, Heemstede, The Netherlands. SUBJECTS: 209 consecutive patients admitted with suspected appendicitis. MAIN OUTCOME MEASURES: Correlation of C reactive protein concentration with age, sex, body temperature, duration of abdominal pain, anorexia, nausea, vomiting, white cell count, neutrophil count, erythrocyte sedimentation rate, and histological appearance of the appendix. RESULTS: 125 patients of the 209 patients had their appendixes removed, and of these 101 had histologically confirmed appendicitis: A C reactive protein concentration of > or = 6 mg/1 alone had a sensitivity of 87% and a specificity of 50%. When the selected variables were subjected to multivariate analysis the most important, in decreasing order, were white blood cell count, female sex, and C reactive protein concentration. Combining the variables was of no additional value. CONCLUSION: measurement of the C reactive protein concentration can increase the accuracy in the diagnosis of acute appendicitis.

Acute Disease↗

A patient with a variant form of hairy cell leukaemia.

A 57-year-old woman was admitted because of weakness, fatigue, abdominal discomfort, easy bruising and splenomegaly. A highly elevated leukocyte count with hairy-cell-like cells was found, the cells being positive for the monoclonal antibodies CD19, FMC7, CD11c and B-ly-7 and negative for CD24 and CD25. Blood and bone marrow were investigated not only in our own laboratory but also in several other laboratories resulting in a variety of possible diagnoses. Only after combining all data could a definitive diagnosis of variant hairy cell leukaemia be made. The patient was treated initially with a splenectomy and later on with interferon-alpha-2b, resulting in a steady decrease in the leukocyte count. After a follow-up of 2 years a nearly complete remission was obtained with a good quality of life. The differential diagnosis of this rare disorder is discussed with emphasis on the relative contribution of different diagnostic procedures.

Diagnosis, Differential↗

Exercise 201Tl scintigraphy: evaluation of the additional diagnostic value.

The additional diagnostic yield of exercise 201Tl scintigraphy using both visual and quantitative analysis was determined in 221 patients with known or suspected coronary artery disease (CAD). The coronary arteriogram was adopted as the gold standard. After pretest clinical and exercise electrocardiographic data were taken into consideration, scintigraphy added diagnostic accuracy both in the diagnosis of CAD and of multivessel disease. The diagnostic yield of the scintigraphy in terms of sensitivity and specificity was, however, not significant. In 79% (121/153) of the patients, the diagnosis of the presence, or exclusion, of CAD was highly probable (P > 0.80 or P < 0.20) when considering clinical and exercise data. The diagnosis was, however, not significantly improved by the scintigraphic result. Twenty-seven per cent (20/73) returned a negative scintigraphic results with a high (P > 0.80) prescintigraphic probability for CAD and a positive arteriogram. It was concluded that 201Tl scintigraphy has additional diagnostic value after clinical and exercise parameters were taken into consideration in the diagnosis of coronary artery and multiple vessel disease. It is not recommended to refer patients with either a low or high probability of CAD for screening and diagnosis as in a high proportion of patients the diagnosis of CAD could have been made using clinical or exercise data alone.

Coronary Disease↗

The clinical impact of thallium-201 reinjection scintigraphy for detection of myocardial viability.

In a clinical study, the value of thallium-201 reinjection was studied in 139 patients with suspected or known coronary artery disease who showed one or more persistent defects after conventional stress-redistribution imaging. Fifty-nine (42%) patients had sustained a Q-wave myocardial infarction. Sixty-eight (49%) patients showed a reversible defect in at least one myocardial segment at redistribution, while 71 (51%) had persistent defects only. Following reinjection additional segmental filling-in was seen in 95 (68%) patients, including 50 of the 68 (74%) patients with reversible defects and 45 of the 71 (63%) with persistent defects only. On the immediately post-exercise images, 458 (47%) of 973 segments showed perfusion defects. At redistribution 105 (23%) of the 458 defects showed filling-in, whereas of the remaining 353 persistent defects 164 (46%) resolved additionally after reinjection. Thirteen (10%) of 133 Q-wave related defects showed filling-in at redistribution compared with 22 (27%) of 82 remote defects (P = 0.001). After reinjection additional filling-in of defects was seen in 47 (39%) of 120 Q-wave related defects compared with 35 (58%) or 60 remote defects (P = 0.015). Overall, 60 (45%) of 133 Q-wave related defects resolved compared with 57 (70%) of 82 remote defects (P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Evaluation of the incremental diagnostic value and impact on patient treatment of thallium scintigraphy.

The incremental diagnostic yield of exercise 201Tl scintigraphy with visual and quantitative analysis was determined in 191 patients with known or suspected coronary artery disease (CAD). The coronary arteriogram was used as the gold standard. After pre-test clinical and exercise electrocardiographic data were taken into consideration, scintigraphy was found to have additional diagnostic value both in the diagnosis of CAD and of multivessel disease, with quantitative analysis being superior to visual analysis. The impact of 201Tl scintigraphy on the patient's treatment--conservative treatment versus revascularization--was also evaluated. The impact was relatively low, as the decision for revascularization was based primarily on the angiographic result and the severity of the anginal pain. This result reflects only the decision making process used in our clinic and permits no conclusion to be made concerning the possible value of 201Tl scintigraphy in this type of medical decision making process.

Coronary Angiography↗

Multivariate statistical modeling: alternative approach to test evaluation, applied to counting reticulocytes by flow cytometry.

We present a statistical path analysis model for the evaluation of two tests in the absence of a "gold standard" method. This model is applied to the evaluation of flow-cytometric and visual reticulocyte counting by using as the comparison method a combination of three hematological measurements: hemoglobin concentration (HGB), mean cellular volume (MCV), and erythrocyte density width (EDW). We assumed that, in general, a higher reticulocyte count is associated with a lower HGB value and with greater values for MCV and EDW. Applying this assumption and the statistical model, we demonstrated that flow cytometry was superior to visual reticulocyte counting in the low-value range studied. The path analysis model is potentially applicable in other cases where two tests are to be compared, and when no gold standard is available.

Erythrocyte Count↗

Bhattacharya: a new application for quality control.

The Bhattacharya method and the 'average of normals' method for internal quality control were compared. Both are based on unselected patient test results. The Bhattacharya method is mostly used in clinical chemistry for calculation of reference intervals but could be modified for quality control procedures. Using the data of a coagulation test and stimulating systematic errors, it was concluded that the Bhattacharya method is more sensitive to expected shifts and is more flexible than the 'average of normals' method.

Blood Coagulation Tests↗

Reference values: Bhattacharya or the method proposed by the IFCC?

The Bhattacharya method was used to calculate reference values from unselected patient data. These values were compared with reference values obtained from data from a blood donor population group following the recommendations of the IFCC. Differences between the results could be attributed in part to different statistical methods, and in part to differences between populations. With some limitations, the Bhattacharya method can be of help in the determination of reference values and quality control.

Blood Chemical Analysis↗