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Abstract omitted due to copyright. [ABSTRACT FROM AUTHOR]

Abstract: Objective: In clinical trials, patients become available for treatment sequentially. Especially in trials with a small number of patients, loss of power may become an important issue, if treatments are not allocated equally or if prognostic factors differ between the treatment groups. We present a new algorithm for sequential allocation of two treatments in small clinical trials, which is concerned with the reduction of both selection bias and imbalance. Study Design and Setting: With the algorithm, an element of chance is added to the treatment as allocated by minimization. The amount of chance depends on the actual amount of imbalance of treatment allocations of the patients already enrolled. The sensitivity to imbalance may be tuned. We performed trial simulations with different numbers of patients and prognostic factors, in which we quantified loss of power and selection bias. Results: With our method, selection bias is smaller than with minimization, and loss of power is lower than with pure randomization or treatment allocation according to a biased coin principle. Conclusion: Our method combines the conflicting aims of reduction of bias by predictability and reduction of loss of power, as a result of imbalance. The method may be of use in small trials. [Copyright &y& Elsevier]

We aimed to establish a rat model of space-occupying hemispheric infarction to evaluate potential treatment strategies. For adequate timing of therapy in future experiments, we studied the development of tissue damage, edema formation, and perfusion over time with different MRI techniques. Permanent middle cerebral artery (MCA) occlusion was performed in 32 Fisher-344 rats. Forty-six MRI experiments including diffusion weighted (DW), T2-weighted (T2W), flow-sensitive alternating inversion recovery (FAIR) perfusion-weighted, and T1-weighted (T1W) imaging before and after gadolinium were performed at 1, 3, 8, 16, 24, and 48 h of ischemia. MCA occlusion consistently led to infarction of the complete MCA territory. Mortality was 75%. Lesion volumes as derived from apparent diffusion coefficient (ADC) and T2 maps increased to maximum values of 400±48 mm3 at 24 h and 420±54 mm3 at 48 h of ischemia, respectively. Midline shift peaked at 24 h. The area with diffusion–perfusion deficit decreased to a minimum at 24 h after onset of ischemia and perfusion of the contralateral hemisphere dropped at the same time point. Leakage of gadolinium through the blood–brain barrier in the entire infarct occurred within 3 h of ischemia. Permanent intraluminal MCA occlusion in Fisher-344 rats is an adequate model for space-occupying cerebral infarction. Rats may benefit from intervention aimed at reducing tissue shift and intracranial pressure (ICP), and at improving cerebral blood flow, if initiated before 24 h after MCA occlusion. The value of treatment modalities depending on an intact blood–brain barrier should be questioned. [Copyright &y& Elsevier]