How a sequential design would have affected the GAIN International Study of gavestinel in stroke

While planning the GAIN International Study of gavestinel in acute stroke, a sequential triangular test was proposed but not implemented. Before the trial commenced it was agreed to evaluate the sequential design retrospectively to evaluate the differences in the resulting analyses, trial durations and sample sizes in order to assess the potential of sequential procedures for future stroke trials. This paper presents four sequential reconstructions of the GAIN study made under various scenarios. For the data as observed, the sequential design would have reduced the trial sample size by 234 patients and shortened its duration by 3 or 4 months. Had the study not achieved a recruitment rate that far exceeded expectation, the advantages of the sequential design would have been much greater. Sequential designs appear to be an attractive option for trials in stroke.     

Responses of earthworms (Lumbricus rubellus) to copper and cadmium as determined by measurement of juvenile traits in a specifically designed test system

In this study, the effects of two metals, copper and cadmium, on the growth and development of juvenile Lumbricus rubellus were measured in a toxicity test in which individuals were grown in isolation. This design had a number of advantages over traditional test systems for earthworms. Importantly, the test is specifically designed to measure two juvenile traits (survival over and length of the juvenile period) that have been shown to have a high sensitivity for determining population growth rate. The test system also maximizes replication, while allowing time-series-based monitoring of individual growth. For both metals, significant exposure-dependent effects on survival, growth, development time, and (less certainly) maturation weight were observed. Comparisons of the relative toxicity of the two metals indicated different concentration-response relationships. For copper, hormesis was found at low levels, while only at the highest soil concentration tested (10.07 micromol g(-1)) were (severe) toxic effects present. For cadmium, hormesis was also evident at the lowest concentration tested; however, at soil levels above this, a graded concentration-dependent toxic effect was apparent. These differences in the exposure response patterns can be (tentatively) explained in terms of the mechanisms for handling copper (an essential metal for earthworms) and cadmium (a putative nonessential element). The applicability of the test for routine measurement of chemical effects on ecologically relevant juvenile traits is also outlined and future developments are discussed.     

Efficient simulation of P values for linkage analysis

In many genetic linkage analyses, the P value is obtained through simulation since the underlying distribution of the test statistic is complex and unknown. However, this can be very computationally intensive. A "bootstrap/replicate pool" approach has been suggested that generates P values more efficiently in terms of computation by resampling sums from a small set of simulated replicates for each pedigree. The replicate pool idea has been successfully applied, but, to our knowledge, has never been theoretically studied. An entirely different method for increasing the computational efficiency of P value simulation is Besag and Clifford's sequential sampling method. We propose an algorithm which combines Besag and Clifford's method with the replicate pool method to efficiently estimate P values for linkage studies. We derive variance expressions for the P value estimates from the replicate pool method and from our proposed hybrid method, and use these to show that the hybrid estimator has a substantial advantage over the other methods in most situations.     

Multiplanar and 3D imaging of the central airways: comparison of image quality and radiation dose of single-detector row CT and multi-detector row CT at differing tube currents in dogs

PURPOSE: To compare in an animal model the image quality of multiplanar reformation and three-dimensional (3D) reconstruction images of the central airways by using single-detector row computed tomography (CT) and multi-detector row CT at varied tube currents and to compare radiation dose. MATERIALS AND METHODS: Five dogs each underwent five consecutive helical CT examinations (one single-detector row CT examination at 240 mA and four multi-detector row CT examinations at 240, 120, 40, and 20 mA), with 0.8-second gantry rotation time. Multiplanar reformation and 3D reconstruction images were created from each of the 25 CT acquisitions. The images were randomized and blindly reviewed with consensus agreement by three radiologists who graded image quality by using a five-point scale. In a separate review, the three radiologists independently used a four-point scale to rank the comparative image quality of the multi-detector row CT 3D images, while blinded to specific tube currents. The radiation doses were measured for each type of scan, and the relative radiation dose length products that were normalized to single-detector row CT values were used to compare radiation doses of the various CT techniques. Statistical analysis was performed with the Wilcoxon signed-rank test and the Friedman analysis of variance test. RESULTS: Image quality was consistently ranked higher for multi-detector row CT images than for single-detector row CT images (P =.03). Although there were no distinguishable differences between images obtained with multi-detector row CT at 240, 120, or 40 mA, images obtained with 20 mA were given a significantly (P =.04) lower relative rank (mean, 2.4) than those obtained with higher tube currents (mean, 1.4-1.7). Multi-detector row CT radiation doses were 1.64, 0.82, 0.27, and 0.14 (for 240-, 120-, 40-, and 20-mA multi-detector row CT, respectively) relative to the dose for 240-mA single-detector row CT. CONCLUSION: Multi-detector row CT is superior to single-detector row CT for multiplanar and 3D imaging of the central airways. Substantial dose reductions can be made, while maintaining high image quality.     

Treatment of early stage breast cancer: do surgeons and patients agree regarding whether treatment alternatives were discussed?

Background. Informing patients of available treatment alternatives is an important element of informed consent. We examined and compared patients' and their surgeons' reports of discussing treatment alternatives for early stage breast cancer. Methods. We surveyed early stage breast cancer patients in two states (Minnesota and Massachusetts) about discussions of breast cancer treatments. We also surveyed their surgeons. We compared how often patients' and surgeons' reports about discussions of treatment alternatives agreed, and we used generalized estimating equations to identify factors related to patients' reports that alternatives were not discussed when their surgeons reported that they were discussed. Results. Among 1154 women eligible for both breast-conserving surgery and mastectomy, only 71% reported that their surgeon discussed both treatments. Surgeons of 730 women returned surveys and reported discussing both treatments with 82% of the patients. One-third of the time, patients and surgeons disagreed about whether both treatments were discussed; with patients more often reporting that both treatments were not discussed when surgeons reported they were. In adjusted analyses, compared to better-educated patients, less-educated patients more often reported that their surgeons did not discuss both treatments when their surgeons reported that they did (compared to non-high school graduates, odds ratio (OR) 0.44, 95% confidence interval (CI) 0.22–0.87 for high school graduates; OR 0.51; 95% CI 0.27–0.96 for women with at least some college education; and OR 0.50; 95% CI 0.20–1.24 for women with any post-graduate work). Conclusion. Patients' and surgeons' reports of treatments discussed often disagree. Interventions to assure that surgeons present and patients fully comprehend treatment options may help to improve the decision-making process, particularly for less well-educated women.