Sample size re-estimation for clinical trials with longitudinal negative binomial counts including time trends

In some diseases, such as multiple sclerosis, lesion counts obtained from magnetic resonance imaging (MRI) are used as markers of disease progression. This leads to longitudinal, and typically overdispersed, count data outcomes in clinical trials. Models for such data invariably include a number of nuisance parameters, which can be difficult to specify at the planning stage, leading to considerable uncertainty in sample size specification. Consequently, blinded sample size re-estimation procedures are used, allowing for an adjustment of the sample size within an ongoing trial by estimating relevant nuisance parameters at an interim point, without compromising trial integrity. To date, the methods available for re-estimation have required an assumption that the mean count is time-constant within patients. We propose a new modeling approach that maintains the advantages of established procedures but allows for general underlying and treatment-specific time trends in the mean response. A simulation study is conducted to assess the effectiveness of blinded sample size re-estimation methods over fixed designs. Sample sizes attained through blinded sample size re-estimation procedures are shown to maintain the desired study power without inflating the Type I error rate and the procedure is demonstrated on MRI data from a recent study in multiple sclerosis.     

The Multimedia activity recall for children and adolescents (MARCA): development and evaluation

Background  

Self-report recall questionnaires are commonly used to measure physical activity, energy expenditure and time use in children and adolescents. However, self-report questionnaires show low to moderate validity, mainly due to inaccuracies in recalling activity in terms of duration and intensity. Aside from recall errors, inaccuracies in estimating energy expenditure from self-report questionnaires are compounded by a lack of data on the energy cost of everyday activities in children and adolescents. This article describes the development of the Multimedia Activity Recall for Children and Adolescents (MARCA), a computer-delivered use-of-time instrument designed to address both the limitations of self-report recall questionnaires in children, and the lack of energy cost data in children.     

Aesthetic refinements in prophylactic mastectomy with immediate reconstruction

Immediate reconstruction of more than 1000 breasts was performed on high-risk patients on whom a prophylactic mastectomy was done. The mastectomy removes as much breast tissue as possible while leaving sufficient skin, and possibly the nipple-areola complex, to enable immediate reconstruction. The creation of symmetrical, well-balanced muscle pockets for the implant is the most important factor in producing satisfactory results in these cases.     

Immediate effects of intravenous clomipramine on sleep and sleep-related secretion in depressed patients

An i.v. challenge dose of clomipramine (12.5 mg) was given to eight outpatients with major depression. The procedure facilitated the examination of all-night sleep and sleep-related neuroendocrine changes (cortisol, growth hormone, and prolactin). In comparison to baseline saline nights, the patients experienced a profound suppression of rapid eye movement (REM) sleep throughout the night with no rebound recovery in the second half of the night. Furthermore, REM-suppressing effects were noted on the following no-drug night. In contrast, little effect on delta wave sleep was found, except for increased consolidation of delta waves within stage 3 and 4 sleep. Delta sleep measures were significantly correlated with levels of cortisol and growth hormone.