A Qualitative Study to Explore Patient Perspectives of Prophylactic Treatment with OnabotulinumtoxinA for Chronic Migraine.

INTRODUCTION: OnabotulinumtoxinA (OBT-A) is one of the most studied prophylactic treatments for chronic migraine. Large clinical trials, and now real-world studies, continue to provide evidence to support the use of OBT-A as an effective treatment to manage chronic migraine. The objective of this study was to explore patient experience and perception of prophylactic treatment with OBT-A for chronic migraine. METHODS: Data were collected using semi-structured interviews using open-ended questions to uncover rich descriptive data on patient experiences. Interviews were transcribed and analysed using NVivo data analysis software to code and identify themes across the dataset. Three patient groups were included in the analysis: (1) patients who were receiving continued OBT-A treatment; (2) patients who discontinued OBT-A treatment; (3) patients who were recommended for OBT-A treatment but did not proceed. RESULTS: For patients who received at least one OBT-A treatment, four main themes emerged, which described patients' expectations, experiences, and feelings towards their treatment decisions. Two main themes emerged that were common to patients, who had discontinued their treatment and those, who were recommended for OBT-A treatment but did not proceed, which were identified as potential barriers to initiate or continue prophylactic treatment with OBT-A. CONCLUSION: Understanding patients' perspective is an important part of clinical practice and may impact on decision-making. Qualitative data can provide a more holistic view of patient care and treatment insights that may not be evaluated during a clinical trial. This study revealed potential barriers to treatment that can inform future policy and practice.

Leveraging supply chain infrastructure to advance patient safety in community health-care settings.

Purpose The purpose of this paper is to examine the opportunity for supply chain processes and infrastructure to reduce the risk of medical error and create traceability of adverse events in community care settings. Patient safety has become an important area of focus over the past few decades, with medical error now accounting for the third most common cause of death in Canada and the USA. The majority of patient safety studies to date have focused specifically on safety in hospital settings; however, deaths and harm experienced by patients in the community (home care, long-term care, complex care and rehabilitation settings) are not well understood. Design/methodology/approach This paper discusses the evidence that adverse events occur at similar, if not more, frequent rates in community care settings. Findings The authors propose that above and beyond current efforts to increase awareness and promote a "safety culture" in health-care settings, system infrastructure should be designed in a way that enables clinicians to provide the safest care possible. There is currently no line of sight across the health-care continuum. The authors suggest that improving system infrastructure would reduce the occurrence of adverse events. Originality/value Such visibility across the continuum of care holds the potential to transform health-care in Canada from a fragmented system, where information is inadequately captured and transferred from provider to provider, to a system that provides complete, accurate and up-to-date information regarding patient care, procedures, medications and outcomes so as to provide the best and safest care possible. System visibility achieves quality and safe care, which is transparent and accountable and achieves value for patients.

Co-targeting AR and HSP90 suppresses prostate cancer cell growth and prevents resistance mechanisms.

Persistent androgen receptor (AR) signaling in castration resistant prostate cancer (CRPC) underpins the urgent need for therapeutic strategies that better target this pathway. Combining classes of agents that target different components of AR signaling has the potential to delay resistance and improve patient outcomes. Many oncoproteins, including the AR, rely on the molecular chaperone heat shock protein 90 (Hsp90) for functional maturation and stability. In this study, enhanced anti-proliferative activity of the Hsp90 inhibitors 17-allylamino-demethoxygeldanamycin (17-AAG) and AUY922 in androgen-sensitive and CRPC cells was achieved when the agents were used in combination with AR antagonists bicalutamide or enzalutamide. Moreover, significant caspase-dependent cell death was achieved using sub-optimal agent doses that individually have no effect. Expression profiling demonstrated regulation of a broadened set of AR target genes with combined 17-AAG and bicalutamide compared with the respective single agent treatments. This enhanced inhibition of AR signaling was accompanied by impaired chromatin binding and nuclear localization of the AR. Importantly, expression of the AR variant AR-V7 that is implicated in resistance to AR antagonists was not induced by combination treatment. Likewise, the heat shock response that is typically elicited with therapeutic doses of Hsp90 inhibitors, and is a potential mediator of resistance to these agents, was significantly reduced by combination treatment. In summary, the co-targeting strategy in this study more effectively inhibits AR signaling than targeting AR or HSP90 alone and prevents induction of key resistance mechanisms in prostate cancer cells. These findings merit further evaluation of this therapeutic strategy to prevent CRPC growth.

Finding the place of histone deacetylase inhibitors in prostate cancer therapy.

Histone deacetylase inhibitors (HDACIs) are showing promise as therapeutic agents for hematological malignancies and solid tumors. In the case of prostate cancer, HDACIs are effective at inhibiting proliferation and inducing apoptosis in a range of in vitro and in vivo experimental models. Recent studies have revealed that the actions of HDACIs in prostate cancer cells extend beyond regulation of histone acetylation and affect proteins involved in maintaining cellular homeostasis and tumor progression, including the androgen receptor, p21(WAF1) and VEGF. The broad spectrum of HDACI targets has allowed rational design of combinations with other therapeutic agents to target multiple pathways involved in prostate cancer progression, including angiogenesis and androgen signaling. In particular, synergistic inhibition of prostate cancer cell growth has been demonstrated using HDACIs in combination with radio- and chemo-therapy, Apo2L/TRAIL, angiogenesis inhibitors, heat-shock protein 90 inhibitors and androgen receptor antagonists. This review examines the current understanding of the actions of HDACIs in prostate cancer cells, both in a laboratory and a clinical context and discusses the potential utility of combination strategies for the treatment of prostate cancer.