We describe an adaptive dose escalation scheme for use in cancer phase I clinical trials. The method is fully adaptive, makes use of all the information available at the time of each dose assignment, and directly addresses the ethical need to control the probability of overdosing. It is designed to approach the maximum tolerated dose as fast as possible subject to the constraint that the predicted proportion of patients who receive an overdose does not exceed a specified value. We conducted simulations to compare the proposed method with four up-and-down designs, two stochastic approximation methods, and with a variant of the continual reassessment method. The results showed the proposed method effective as a means to control the frequency of overdosing. Relative to the continual reassessment method, our scheme overdosed a smaller proportion of patients, exhibited fewer toxicities and estimated the maximum tolerated dose with comparable accuracy. When compared to the non-parametric schemes, our method treated fewer patients at either subtherapeutic or severely toxic dose levels, treated more patients at optimal dose levels and estimated the maximum tolerated dose with smaller average bias and mean squared error. Hence, the proposed method is promising alternative to currently used cancer phase I clinical trial designs.

Concepts from the health belief, transtheoretical, and dual process models were used to examine how siblings of individuals diagnosed with colorectal cancer (CRC) before age 56 made decisions about CRC screening. Siblings (N = 504) were assessed for CRC screening practices and intentions, pros, cons, processes-of-change, perceived risk of CRC, perceived severity of CRC, preventability of CRC, cancer-related distress, and sibling relationship closeness. Physician and family recommendation and knowledge were also assessed. Fifty-seven percent of participants (n = 287) were compliant with CRC screening. Logistic regression indicated that perceived pros and cons, perceived risk, commitment to screening, health care avoidance, and sibling closeness were associated with screening compliance. Physician and family recommendation were also strong correlates. A similar set of factors was associated with stage of adoption of CRC screening.

In this study, venous oxygen saturation and oxygen metabolic changes in multiple sclerosis (MS) patients were assessed using a recently developed T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging (MRI), which measures the superior sagittal venous sinus blood oxygenation (Yv) and cerebral metabolic rate of oxygen (CMRO 2 ), an index of global oxygen consumption. Thirty patients with relapsing-remitting MS and 30 age-matched healthy controls were studied using TRUST at 3 T MR. The mean expanded disability status scale (EDSS) of the patients was 2.3 (range, 0 to 5.5). We found significantly increased Yv (P < 0.0001) and decreased CMRO 2 (P = 0.003) in MS patients (mean±s.d.: 65.9%±5.1% and 138.8±35.4 lmol per 100 g per minute) as compared with healthy control subjects (60.2% ± 4.0% and 180.2 ± 24.8 lmol per 100 g per minute, respectively), implying decrease of oxygen consumption in MS. There was a significant positive correlation between Yv and EDSS and between Yv and lesion load in MS patients (n = 30); on the contrary, there was a significant negative correlation between CMRO 2 and EDSS and between CMRO 2 and lesion load (n = 12). There was no correlation between Yv and brain atrophy measures. This study showed preliminary evidence of the potential utility of TRUST in global oxygen metabolism. Our results of significant underutilization of oxygen in MS raise important questions regarding mitochondrial respiratory dysfunction and neurodegeneration of the disease.

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