Two-stage transformation systems for normalization of reference distributions evaluated

In two-stage transformation systems for normalization of reference distributions, the asymmetry is first corrected, and any deviation of kurtosis is then adjusted. The simulation studies reported here show that these systems have previously been assessed too optimistically because the sample variation of the transformation parameters was neglected. Applying a goodness-of-fit test to transformed values shows that one should accept gaussianity only for p-values greater than 0.15 instead of those greater than 0.05. Further, the calculated 90% confidence intervals of reference limits should be expanded by 25%. When the correct level of significance is used, only real reference distributions that deviate moderately from the gaussian form are normalized. Calculation of confidence intervals demonstrated that 50 to 450 subjects are needed for a precise parametric estimation of the 95% reference interval. For the nonparametric approach, 125 to 700 reference subjects are necessary. The larger sample sizes are needed when distributions show pronounced skewness.     

Influence of complement on sperm motility

Isolated sperm from normo-, oligo- and astheno-spermic men were incubated for 20 h in medium supplemented with 8% heat-inactivated or untreated human serum, and in medium with heated or untreated serum deficient in complement factor C3. Before and after incubation, sperm motility was assessed by means of a computer-assisted semen analyser. The results did not show significant differences between the motility of sperm incubated in heated or untreated serum. It is concluded that heating of homologous serum is not necessary for preserving sperm motility and in some cases may even be disadvantageous.     

A review on the methodology for assessing diagnostic tests

Evaluation of diagnostic tests by the following principles are reviewed: error rates, scores based on posterior probabilities, and the excess loss considered in a decision theoretic context. Error rates or the complementary non-error rates, specificity and sensitivity, are simple measures which provide a rough indication of the discriminative value. In clinical practice, where a test serves as a decision support together with other information, conversion of test results to posterior probabilities is recommended. An aggregate score of these probabilities expresses the value of the test. Finally, in simple, well-defined cases--for example, screening situations, where the prevalence of disease and the relative consequences of false-positive and -negative classifications can be estimated--a Bayesian decision analysis is appropriate. The optimal discrimination limit is selected, and the total loss is minimized. The likelihood ratio LR(x) plays a central role in probability calculations and in the decision analysis. An example illustrates application of the procedures.     

Image-directed percutaneous biopsies with a biopsy gun

Core tissue for histologic study is believed by many pathologists to be more diagnostic than material from needle aspiration. Recently, a biopsy "gun" has been introduced, which simplifies core biopsies. With this device, 182 biopsies of multiple anatomic sites were performed with ultrasonic, computed tomographic, and fluoroscopic guidance and 18-gauge needles. High-quality histopathologic specimens were obtained in 177 of the biopsies, and diagnostic target tissue was obtained in 167. Only three significant complications occurred: one bleeding complication that required transfusion and two cases of pneumothorax that necessitated placement of chest tubes. The biopsy gun eliminated the disjointed movements of conventional "skinny" needle biopsies, and none of the samples demonstrated significant "crush" artifact or obscuring blood, problems that are commonly associated with manual biopsy techniques. Patient discomfort was decreased with this system compared with that of manual biopsies, and the total procedure time was reduced. Because of these distinct advantages, the authors now use the biopsy gun exclusively for all percutaneous biopsies and recommend that other institutions consider the use of this biopsy method.     

Mean and variance rules are more powerful or selective than quality control rules based on individual values

Quality control rules based on individual values are compared with mean and variance rules using theoretical computations and simulations. Simple (1(3)s) and combined individual value rules, e. g. a 1(3)s/2(2)s/4(1)s/6 means rule, are all less powerful for detection of shifts of location than a mean rule, given identical type I errors. The mean rule is also more robust towards non-normality of data distributions. In most cases, the variance rule has more power towards increased scatter than individual value rules, and it always has the highest selectivity. Thus, the simple computations that are required for derivation of the mean and variance result in increased power or selectivity. In particular, in the computerization of quality control, the traditional mean and variance rules are preferable to more or less complicated "multi-rules" proposed for computerized quality control.     

Gestational age, birth weight, and the risk of hyperkinetic disorder.

AIMS: To study the association between gestational age and birth weight and the risk of clinically verified hyperkinetic disorder. METHODS: Nested case-control study of 834 cases and 20 100 controls with incidence density sampling. RESULTS: Compared with children born at term, children born with gestational ages of 34-36 completed weeks had a 70% increased risk of hyperkinetic disorder (rate ratio (RR) 1.7, 95% confidence interval (CI) 1.2 to 2.5). Children with gestational ages below 34 completed weeks had an almost threefold increased risk (RR 2.7, 95% CI 1.8 to 4.1). Children born at term with birth weights of 1500-2499 g had a 90% increased risk of hyperkinetic disorder (RR 1.9, 95% CI 1.2 to 2.9), and children with birth weights of 2500-2999 g had a 50% increased risk (RR 1.5, 95% CI 1.2 to 1.8) compared with children born at term with birth weights above 2999 g. The results were adjusted for socioeconomic status of the parents, family history of psychiatric disorders, conduct disorders, comorbidity, and maternal smoking during pregnancy. Results related to birth weight were unchanged after adjusting for differences in gestational age. CONCLUSIONS: Children born preterm, also close to term, and children born at term with low birth weights (1500-2499 g) have an increased risk of clinically verified hyperkinetic disorder. These findings have important public health perspectives because the majority of preterm babies are born close to term.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.