Impaired Knowledge of Social Norms in Dementia and Psychiatric Disorders: Validation of the Social Norms Questionnaire-Dutch Version (SNQ-NL).

The Social Norms Questionnaire-Dutch version (SNQ-NL) measures the ability to understand and identify social boundaries. We examined the psychometric characteristics of the SNQ-NL and its ability to differentiate between patients with behavioral variant frontotemporal dementia (bvFTD; n = 23), Alzheimer's dementia (AD; n = 26), chronic psychiatric disorders (n = 27), and control participants (n = 92). Between-group differences in the Total score, Break errors, and Overadhere errors were examined and associations with demographic variables and other cognitive functions were explored. Results showed that the SNQ-NL Total Score and Break errors differed between patients with AD and bvFTD, but not between patients with bvFTD and psychiatric disorders. Modest correlations with age, sex, and education were observed. The SNQ-NL Total score and Break errors correlated significantly with emotion recognition and verbal fluency but not with processing speed or mental flexibility. In conclusion, the SNQ-NL has sufficient construct validity and can be used to investigate knowledge of social norms in clinical populations.

Successful treatment of leptomeningeally metastasised pituitary carcinoma with temozolomide.

A 69-year-old man presented with leptomeningeally metastasised pituitary carcinoma, rapidly progressing despite previous treatment with resection, radiotherapy and cabergoline. The patient received temozolomide chemotherapy, resulting in a complete clinical, radiological and biochemical response after 14 cycles, which has been maintained since then. This case lends further support to the role of temozolomide in refractory pituitary tumours.

Towards better dose individualisation: metabolic phenotyping to predict cabazitaxel pharmacokinetics in men with prostate cancer.

BACKGROUND: Cabazitaxel is approved for treatment of castration-resistant metastatic prostate cancer. The current dosing strategy of cabazitaxel is based on body surface area (BSA). Body surface area is known as a poor predictor for total systemic exposure to drugs, since it does not take into account variability in activity of metabolising enzymes, necessary for clearance of drugs. As exposure to cabazitaxel is related to treatment response, it is essential to develop a better individualised dosing strategy. METHODS: Ten patients with metastatic castration-resistant prostate cancer, who received cabazitaxel dosed on BSA as a part of routine palliative care, were enrolled in this study. Midazolam was administered as phenotyping probe for cytochrome P450 isoenzyme 3A (CYP3A). The relationship between midazolam and cabazitaxel clearance was investigated using non-linear mixed effects modelling. RESULTS: The clearance of Midazolam highly correlated with cabazitaxel clearance (R=0.74). Midazolam clearance significantly (P<0.004) explained the majority (∼60%) of the inter-individual variability in cabazitaxel clearance in the studied population. CONCLUSIONS: Metabolic phenotyping of CYP3A using midazolam is a promising strategy to individualise cabazitaxel dosing. Before clinical application, a randomised study is warranted.