Contraceptive Implanon: Why do GPs get asked to remove it early?

Nineteen women aged 18 to 39 years of age from four Coast City Country GP Training practices were interviewed regarding their experiences with Implanon and the reasons for early removal. All participants were in relationships and approximately half had children

Patient perspectives about why they ask to remove their contraceptive Implanon® device early

Background Women with long-acting, reversible contraceptive devices inserted may choose to remove them prior to their planned expiry dates. Objective/s The objective of this study was to explore Australian women\u27s experiences with the etonogestrel subdermal contraceptive implant (Implanon NXT) and why they had it removed early. Methods Semi-structured interviews were conducted with 18 women between June 2013 and January 2014. Transcriptions of the audio-taped interviews were analysed using a constant comparative analysis framework. ResultsTwo core themes of participants\u27 responses that were identified in this study were influences on choice of contraception, which included convenience and information sources; and influences on removal of contraception, which included side effects and their negative impacts on relationships and financial costs. Discussion This study highlights that women\u27s experiences with side effects contribute to the early removal of long-acting contraceptive devices such as Implanon NXT. This study emphasises the importance of general practitioners (GPs) in providing comprehensive information about the benefits and potential side effects associated with using these implants

BDA-366, a putative Bcl-2 BH4 domain antagonist, induces apoptosis independently of Bcl-2 in a variety of cancer cell models

Several cancer cell types, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL) upregulate antiapoptotic Bcl-2 to cope with oncogenic stress. BH3 mimetics targeting Bcl-2's hydrophobic cleft have been developed, including venetoclax as a promising anticancer precision medicine for treating CLL patients. Recently, BDA-366 was identified as a small molecule BH4-domain antagonist that could kill lung cancer and multiple myeloma cells. BDA-366 was proposed to switch Bcl-2 from an antiapoptotic into a proapoptotic protein, thereby activating Bax and inducing apoptosis. Here, we scrutinized the therapeutic potential and mechanism of action of BDA-366 in CLL and DLBCL. Although BDA-366 displayed selective toxicity against both cell types, the BDA-366-induced cell death did not correlate with Bcl-2-protein levels and also occurred in the absence of Bcl-2. Moreover, although BDA-366 provoked Bax activation, it did neither directly activate Bax nor switch Bcl-2 into a Bax-activating protein in in vitro Bax/liposome assays. Instead, in primary CLL cells and DLBCL cell lines, BDA-366 inhibited the activity of the PI3K/AKT pathway, resulted in Bcl-2 dephosphorylation and reduced Mcl-1-protein levels without affecting the levels of Bcl-2 or Bcl-xL. Hence, our work challenges the current view that BDA-366 is a BH4-domain antagonist of Bcl-2 that turns Bcl-2 into a pro-apoptotic protein. Rather, our results indicate that other mechanisms beyond switching Bcl-2 conformation underlie BDA-366's cell-death properties that may implicate Mcl-1 downregulation and/or Bcl-2 dephosphorylation.status: publishe