Down syndrome: Distribution of brain amyloid in mild cognitive impairment.

INTRODUCTION: Down syndrome (DS) is associated with a higher risk of dementia. We hypothesize that amyloid beta (Aß) in specific brain regions differentiates mild cognitive impairment in DS (MCI-DS) and test these hypotheses using cross-sectional and longitudinal data. METHODS: 18F-AV-45 (florbetapir) positron emission tomography (PET) data were collected to analyze amyloid burden in 58 participants clinically classified as cognitively stable (CS) or MCI-DS and 12 longitudinal CS participants. RESULTS: The study confirmed our hypotheses of increased amyloid in inferior parietal, lateral occipital, and superior frontal regions as the main effects differentiating MCI-DS from the CS groups. The largest annualized amyloid increases in longitudinal CS data were in the rostral middle frontal, superior frontal, superior/middle temporal, and posterior cingulate cortices. DISCUSSION: This study helps us to understand amyloid in the MCI-DS transitional state between cognitively stable aging and frank dementia in DS. The spatial distribution of Aß may be a reliable indicator of MCI-DS in DS.

Cost-efficacy of imatinib versus allogeneic bone marrow transplantation with a matched unrelated donor in the treatment of chronic myelogenous leukemia: a decision-analytic approach.

STUDY OBJECTIVE: To develop and populate a decision-analytic model for comparing the 2-year cost and efficacy of imatinib versus allogeneic bone marrow transplantation (BMT) with a matched unrelated donor in the treatment of a 35-year-old man with newly diagnosed, Philadelphia chromosome-positive (Ph[+]) chronic myelogenous leukemia (CML) in the chronic phase. DESIGN: Markov cohort analysis and first-order Monte Carlo microsimulation. MEASUREMENTS AND MAIN RESULTS: Direct medical costs were measured from the perspective of a third-party payer. Efficacy data and probabilities were obtained from survivability findings, most of which were derived from randomized controlled trials. We employed a 2-year time horizon with 3-month treatment cycles. The comparator was BMT with a matched unrelated donor, and the base case was defined as a 35-year-old, Ph(+) man with newly diagnosed CML. The Monte Carlo microsimulation indicated that the incremental cost:efficacy ratio was -$5000 for imatinib (95% confidence interval -$70,000-84,000). Analysis of the cost-efficacy plane revealed that imatinib was dominant over BMT in 84.69% of cases, whereas BMT dominated imatinib in 0.76% of cases. Trade-offs were warranted in the remaining cases. Sensitivity analyses of costs and discount rates found these results to be generally robust. CONCLUSION: In most cases, imatinib was both less costly and more efficacious than BMT in the 2-year treatment of CML. Results of this investigation should be viewed in the context of emerging long-term clinical data. These data are necessary to assess cost-efficacy beyond the short-term time horizon of this study.

Implementation and results of a test dose program with taxanes.

PURPOSE: A pilot taxane test-dose policy was developed and implemented to determine whether the severity of patient hypersensitivity reaction and drug waste would be reduced. PATIENTS AND METHODS: Data from 206 eligible cancer patients undergoing first-dose taxane chemotherapy were analyzed. The severity of hypersensitivity reactions before and after the implementation of taxane test dose was graded (scale 1-4) and analyzed for statistical differences between groups. Average drug wastage was calculated before and after program initiation. RESULTS: Twenty-two of 206 patients (10.7%) experienced a hypersensitivity reaction. The mean hypersensitivity reaction severity for reacting patients who did not receive a test dose (N = 12) was 3.3, and for those who were given a test dose (N = 10), it was 1.5. Only one of five patients who experienced a hypersensitivity reaction that required hospitalization was from the test-dose group. The value of drug alone wasted before test-dose utilization was about $1794 per reacting patient, and the use of taxane test doses saved approximately $1784 per reacting individual. This represented more than a $178 savings for every patient receiving a taxane for the first time. These figures do not include resuscitation, hospital, and other subsequent other costs associated with morbidity. CONCLUSIONS: Implementation of a taxane test-dose policy significantly reduced hypersensitivity reaction severity, drug wastage, and hospitalizations.