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.     

A reassessment of the peritoneal lavage leukocyte count in blunt abdominal trauma

Nine hundred and three patients undergoing diagnostic peritoneal lavage (DPL) over a 6-year period were retrospectively reviewed to evaluate the utility of the white blood cell (WBC) count in the lavage fluid. Eleven patients (1.2%) had dialysate WBC counts greater than 500/mm3, with erythrocyte counts less than 10(5)/mm3. Nine of these patients who were lavaged within 4 hours of injury had no intra-abdominal pathology. Two patients, lavaged after 4 hours, demonstrated intra-abdominal injury. Two hundred twenty-three patients (24.7%) had grossly clear dialysate which was not sent for laboratory analysis. None of these patients required laparotomy. We conclude that the WBC count in DPL fluid is of no diagnostic value in victims of blunt abdominal trauma who are lavaged within 4 hours of injury. In addition, laboratory analysis of clear dialysate is not required in these patients.