One‐ and two‐stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint

Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single‐ordered categorical endpoint. The sample size requirements for one‐stage and two‐stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered. Copyright © 2008 John Wiley & Sons, Ltd.     

When work strain transcends psychological boundaries: an inquiry into the relationship between time pressure,irritation, work–family conflict and psychosomatic complaints

Against the theoretical background of the effort–recovery model and the action regulation theory, the author presents a cross‐sectional questionnaire study testing hypotheses about the relationship between work‐related time pressure, cognitive and emotional irritation, work–family conflict and psychosomatic complaints. Subjects were 576 female home care nurses. Results of a path analysis show that the relation of time pressure and psychosomatic complaints is partially mediated by experiencing a work–family conflict; also the relation of time pressure and work–family conflict is partially mediated by cognitive and emotional irritation. It is argued that cognitive and emotional irritation are fruitful concepts for a more comprehensive understanding of the relationship between work stressors and the development of strain‐based work–family conflict. Implications for the prevention of work–family conflict are outlined. Copyright © 2008 John Wiley & Sons, Ltd.     

Short-term complications and resource utilization in matched subjects after on-pump or off-pump primary isolated coronary artery bypass.

BACKGROUND: Studies suggest that patients who undergo off-pump coronary artery bypass grafting (OPCABG) have fewer short-term complications and use fewer inpatient resources than do patients who undergo standard coronary artery bypass grafting (CABG) with extracorporeal circulation. However, dissimilarity between groups in risk factors for complications has hindered interpretation of results. OBJECTIVES: To compare the prevalence of selected complications (atrial fibrillation, stroke, reoperation, and bleeding) and inpatient resource utilization (length of stay, discharge disposition, total charges) between subjects undergoing primary isolated CABG or OPCABG who were matched with respect to key risk factors. METHODS: Retrospective, causal-comparative survey conducted in 1 center for 18 months. Patients who underwent primary isolated CABG or OPCABG were matched for sex, age (within 2 years), left ventricular ejection fraction (within 0.05), and graft-patient ratio (exact match) and compared for prevalence of new-onset atrial fibrillation, stroke, reoperation within 24 hours, and bleeding. Statistical analysis included Wilcoxon and t tests for paired comparisons. RESULTS: The sample (107 matched pairs) was 63% male, with a mean age of 66 (SD 9.5) years, a mean left ventricular ejection fraction of 0.51 (SD 0.13), and a mean graft-patient ratio of 3.41 (SD 0.74). The 2 groups did not differ significantly in New York Heart Association class (P = .43), Acute Physiology and Chronic Health Evaluation III score (P = .22), postoperative beta-blocker use (P = .73), or comorbid conditions. None of the complications examined differed significantly between pairs. CONCLUSION: Patients with comparable risk profiles have similar prevalences of selected complications after CABG and OPCABG.     

Enamel loss associated with orthodontic adhesive removal on teeth with white spot lesions: an in vitro study.

Teeth with white spot lesions (WSL) might be more prone to enamel loss during bracket debonding. This in vitro study compared enamel loss from teeth with (n = 14) and without (n = 14) WSL after polishing with low-speed finishing burs or disks (Sof-Lex, 3M ESPE, St Paul, Minn). Debonded surfaces were analyzed with a contact stylus profilometer, and digitized data were compared with baseline readings by using AnSur NT software (Regents, University of Minnesota, Minneapolis, Minn). Specimen surfaces were also examined with a scanning electron microscope. Two-way analysis of variance was performed to analyze the data. In teeth without WSL, the volume losses were 0.16 mm(3) for the bur group and 0.10 mm(3) for the disk group; the mean maximum depths were 47.7 microm for the bur group and 54.3 microm for the disk group. In teeth with WSL, the volume losses were 0.06 and 0.17 mm(3), and the mean maximum depths were 35.1 and 48.7 microm for the bur and disk groups, respectively. There were no significant differences in enamel loss between the 2 groups of teeth without WSL (P =.12). However, in teeth with WSL, the burs removed less enamel than the disks (P = 0.006). Scanning electron microscope examination showed that any damage on the enamel surface was usually located in the cervical third of the teeth. On most specimens, even though tooth surfaces appeared resin-free to the naked eye, there were remnants of it. The differences between groups were so small that they might be clinically insignificant.     

Evidence for motility and pinocytosis in ramified microglia in tissue culture

Ramified microglial cells were investigated in primary cultures of dissociated cerebral cortical tissue from rats. The identification of these cells was confirmed through immunohistochemical staining with 7 monoclonal antibodies selective for microglia. While there was significant variation in staining intensity with different antibodies, all stained the identified ramified cells; the antibodies OX-42 and ED1 yielded the most intense immunoreactivity. Based on distinctive morphological features, the microglia could be identified in living cultures where they were monitored using time-lapse video recording. This technique revealed extremely dynamic features of cellular plasticity and motility. Ramified microglia exhibited constant and rapid alterations in the size and shape of their cell body with an associated extension and retraction of processes; concomitantly, the cells moved about in a circumscribed area. These features of plasticity and motility were unique to this cell type, and correlated with OX-42 immunostaining. The microglia also possessed a differentially high level of pinocytotic activity; this too was correlated with OX-42 staining. From the nature of their morphological plasticity and motility, high pinocytosis, and cellular distribution, it is hypothesized that the ramified microglia specifically function as a system of fluid cleansing in normal brain tissue.