Persistence with mirabegron therapy for overactive bladder: A real life experience.

AIMS: To evaluate persistence rates of patients receiving mirabegron therapy for overactive bladder (OAB) within our institution over a 6 month period, identify determinants of early discontinuation of therapy, and assess overall patient satisfaction with treatment. METHODS: Hospital prescription data were analyzed in order to identify all patients who had been prescribed mirabegron in our institution. Case notes were retrospectively reviewed to obtain demographic data, previous treatments for OAB, reasons for discontinuation of previous treatments, and duration of treatment with mirabegron. Overall satisfaction with treatment was assessed using the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q). RESULTS: One hundred and ninety-seven patients were prescribed mirabegron. Of these, 81% previously discontinued anticholinergic therapy, 14% had previously received intravesical botulinum toxin A therapy, and 19% were prescribed mirabegron first-line. At 3 months 69% persisted with treatment which fell to 48% by 6 months. The commonest reason for discontinuation was lack of efficacy, followed by adverse effects. Overall 32% of patients preferred mirabegron over previous treatments and only 39% were satisfied with mirabegron therapy. CONCLUSION: Persistence rates with mirabegron in this group of patients for OAB are satisfactory. The commonest reasons for discontinuation are unmet treatment expectations and adverse effects. We had very few treatment-naïve patients and so further studies are required to assess mirabegron persistence rates with longer-term follow up, as first-line treatment and in different groups of OAB severity. Neurourol. Neurourol. Urodynam. 36:404-408, 2017. © 2015 Wiley Periodicals, Inc.

Long-term genistein treatment of MCF-7 cells decreases acetylated histone 3 expression and alters growth responses to mitogens and histone deacetylase inhibitors.

Defects in epigenetic regulation of gene transcription play an important role in carcinogenesis of the breast and other tissues. The two most widely studied epigenetic changes are DNA methylation and acetylation of histone proteins and inhibition of these processes inhibits growth in breast cancer cell lines. These data coupled with the evidence that fetal and neonatal exposure to oestrogenic substances may lead to epigenetic changes that predispose or protect against the development of breast cancer in later life formed the basis for this study. Three histone deacetylases, valproic acid (VPA), trichostatin A (TCA) and apicidin dose-dependently inhibited basal growth in MCF-7 and MDA-MB-231 as well as the growth promoting effects of oestradiol (E(2)) and epidermal growth factor (EGF) in MCF-7 cells. The growth inhibitory responses to the DNA methyl transferase inhibitor, 5-aza-2'deoxycytidine (decitabine) were weak. HDACi's reduced the protein levels of pro-caspase 9 and cyclin D1, whereas decitabine had no effect. Long-term genistein treatment (LTGT) of MCF-7 cells markedly reduced the basal expression of acetylated histone 3 (H3) and the effects of HDACi's on increasing the levels of acetylated H3 protein. However, this was not correlated with a reduced expression of total H3 except after a high dose of VPA. LTGT inhibited growth of MCF-7 cells and the mitogenic responses to E(2) and EGF. The growth inhibitory responses to HDACI's in the presence of E(2) and EGF was significantly reduced in LTGT cells compared to control MCF-7 cells and there was evidence that LTGT maintained the protein levels of pro-caspase 9 in the presence of HDACi's. This study provides further evidence that oestrogenic substances can induce significant epigenetic changes to alter the dynamics of growth in breast cancer cell lines.