A web-based decision aid for shared decision making in pelvic organ prolapse: the SHADE-POP trial.

INTRODUCTION AND HYPOTHESIS: Among women worldwide, pelvic organ prolapse (POP) is a common problem. There are three different treatment options for POP: pelvic floor muscle therapy, pessary treatment and prolapse surgery. As none of the three treatment options is clearly superior, shared decision making (SDM) is very important. A decision aid (DA) is known to facilitate patient participation and SDM. We hypothesise that the use of a web-based DA for POP increases patients' satisfaction with information and care and reduces decisional conflict. METHODS: This two-arm, multicentre, cluster randomised controlled trial was performed in women with POP in five different Dutch hospitals. The control group received usual care (UC) and the intervention group received the DA in addition to UC. Primary outcome measures were satisfaction with treatment decision making and satisfaction with information. Analyses were performed using independent sample t tests, Chi-squared tests, and multilevel linear regression analyses. RESULTS: Between the DA group (n=40) and the UC group (n=56) no differences were found concerning patients' satisfaction with information, with scores of 45.63 and 46.14 out of 50 respectively (p=0.67). Also, no differences were found concerning the perceived role in decision making, as patients scored 46.83 in the DA group and 46.41 in the UC group, out of a maximum of 54 (n=0.81). CONCLUSIONS: No differences were found concerning patients' satisfaction with information and treatment decision making between the DA and UC. However, both groups scored high on the questionnaires, which suggests that the decision process is already of high quality.

Interactions of deoxynivalenol and lipopolysaccharides on cytotoxicity protein synthesis and metabolism of DON in porcine hepatocytes and Kupffer cell enriched hepatocyte cultures.

The cytotoxicity of deoxynivalenol (DON), effects on protein synthesis and albumin secretion was investigated in porcine hepatocytes and Kupffer cell-enriched hepatocyte cultures (co-cultures) in the presence and absence of lipopolysaccharides (LPS). Up to 16microM DON did not reduce the metabolic activity of hepatocytes. Lysosomal activity reacted more sensitively as neutral red uptake was decreased starting at 2 or 4microM DON irrespective of LPS exposure. The synthesis of secreted proteins was reduced to 31% and 42%, and of cellular proteins to 47% and 39%, in the absence and presence of LPS, respectively, when hepatocytes were exposed to 2microM DON. Reduced albumin secretion in response to DON was already observed after 3h in hepatocytes as well as co-cultures while LPS-mediated decrease was not evident until 24h, when interactions between DON and LPS resulted from a diminishing difference between LPS stimulated and non-stimulated cultures with increasing concentrations of DON. All observed effects may be biased by the cells' ability to conjugate DON to glucuronic acid as 54% and 64% of DON administered at 5nM were recovered as conjugates after 48h. Glucuronidation rate, as well as total DON recovery, decreased with increasing concentrations of DON, giving rise to assumptions on the formation of undetected metabolites.

Deoxynivalenol-induced cytotoxicity, cytokines and related genes in unstimulated or lipopolysaccharide stimulated primary porcine macrophages.

The cytotoxicity of deoxynivalenol (DON) as well as the induction of cytokines and related genes was investigated in porcine pulmonary alveolar macrophages (PAM) in absence or presence of lipopolysaccharides (LPS). IC(20) values were 1.1, 0.4 and 1.0microM DON in the MTT, neutral red and alamar blue assay, respectively, and did not differ significantly in the presence of LPS. The mRNA expression of tumour necrosis factor (TNF)-alpha peaked at 3h, whereas LPS and DON showed synergistic effects resulting in an approximately 20-fold increase at 500nM DON as compared to untreated controls. The supernatant concentrations of TNF-alpha showed similar synergistic effects. The expression of interleukin (IL)-1beta was significantly induced by DON (except for 12h) and LPS. An induction of the mRNA expression of IL-6 by DON was evident only at 3h, whereas the supernatant concentrations of LPS stimulated PAM incubated with 500nM DON were significantly decreased at most time points. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression did not seem to contribute to the effects of DON in porcine macrophages. The results of the present investigation suggest a contribution of cytokines, especially TNF-alpha and IL-1beta, induced by DON in porcine macrophages to the effects observed in vivo.

Implications of ABC transporters on the disposition of typical veterinary medicinal products.

The ATP-Binding Cassette (ABC) transporters ABCB1, ABCC2 and ABCG2 are efflux transporters that facilitate the excretion of drugs, contribute to the function of biological barriers and maintain low cytoplasmic substrate concentrations in cells. ABC transporters modulate drug absorption, distribution and elimination according to the level of expression in the intestine, liver, kidney, and at biological barriers such as the blood-brain barrier. Moreover individual transporters are known to convey multi-drug resistance to tumour cells. While these diverse functions have been described in laboratory animal studies and in humans, the available information is very limited in animal species that are typical veterinary patients. This brief review summarizes the available data on organ distribution and expression levels in animals, genetic defects in dogs resulting in a non-functional P-gp expression, and describes examples of kinetic investigations directed to assess the clinical relevance of species differences in ABC-transporter expression.