Are neurocognitive speed and inconsistency similarly affected in type 2 diabetes?

Type 2 diabetes (T2D) is a disease of aging with indirect but detectable and cumulative neurological implications. We systematically tested whether neurocognitive speed (mean rate) or inconsistency (intraindividual variability) was the more sensitive clinical marker of T2D. Three of four research questions used a cross-sectional wave of the Victoria Longitudinal Study (VLS) divided into T2D (age 55-81 years) and control (age = 53-91 years) groups. The fourth question addressed relative two-wave longitudinal changes. Each of four speeded tasks produced intraindividual mean rate (IM) and intraindividual standard deviation (ISD) scores. First, the T2D group performed more slowly than the controls. Second, this deficit extended to inconsistency, but less uniformly. Third, based on logistic regression analyses, IM was the more effective predictor of T2D status. Fourth, we observed similar longitudinal change patterns for IM and ISD. Results are linked to the theoretical location of T2D on an adjusted neural vulnerability continuum.

Effects of food on the relative bioavailability of lapatinib in cancer patients.

PURPOSE: This study was conducted to characterize the effect of food on the relative bioavailability of lapatinib. PATIENTS AND METHODS: A single 1,500-mg, oral dose of lapatinib was administered to 27 patients with advanced solid tumors on each of three occasions that were 1 week apart, in random order: after an overnight fast, with a low-fat breakfast, and with a high-fat breakfast. RESULTS: The low-fat breakfast produced mean increases in lapatinib area under the concentration-time curve (AUC) of 167% (2.67-fold) and maximum concentration (C(max)) of 142% (2.42-fold). The high-fat breakfast produced mean increases in lapatinib AUC of 325% (4.25-fold) and C(max) of 203% (3.03-fold) compared with the fasted state. Increased bioavailability in the fed state did not significantly decrease relative variability. Therefore, absolute variability in systemic exposure was increased. CONCLUSION: These large increases in lapatinib bioavailability and absolute variability support the recommendation for dosing in the fasted state to achieve consistent therapeutic exposure. Prescribers and patients should consider the potential consequences of toxicity or diminished efficacy that might result from dosing without regard to variations in diet.