Small molecule recognition of mephedrone using an anthracene molecular clip

This document is the Accepted Manuscript version of the following article: Kathryn Kellett, J. Hugh Broome, Mire Zloh, Stewart B. Kirton, Suzanne Fergus, Ute Gerhard, Jacqueline Stair, and Kar J. Wallace, ‘Small molecule recognition of mephedrone using an anthracene molecular clip’, Chemical Communications, Vol. 52(47): 7474-7477, 2016. The version of record is available online at DOI: http://dx.doi.org/10.1039/C6CC03404G. Published by the Royal Society of Chemistry.An anthracene molecular probe has been synthesised and shown to target mephedrone, a stimulant drug from the cathinone class of new psychoactive substances (NPS). A protocol has been developed to detect mephedrone via the probe using NMR spectroscopy in a simulated street sample containing two of the most common cutting agents, benzocaine and caffeine.Peer reviewedFinal Accepted Versio

Early fibrinogen concentrate therapy for major haemorrhage in trauma (E-FIT 1): results from a UK multi-centre, randomised, double blind, placebo-controlled pilot trial.

BACKGROUND: There is increasing interest in the timely administration of concentrated sources of fibrinogen to patients with major traumatic bleeding. Following evaluation of early cryoprecipitate in the CRYOSTAT 1 trial, we explored the use of fibrinogen concentrate, which may have advantages of more rapid administration in acute haemorrhage. The aims of this pragmatic study were to assess the feasibility of fibrinogen concentrate administration within 45 minutes of hospital admission and to quantify efficacy in maintaining fibrinogen levels ≥ 2 g/L during active haemorrhage. METHODS: We conducted a blinded, randomised, placebo-controlled trial at five UK major trauma centres with adult trauma patients with active bleeding who required activation of the major haemorrhage protocol. Participants were randomised to standard major haemorrhage therapy plus 6 g of fibrinogen concentrate or placebo. RESULTS: Twenty-seven of 39 participants (69%; 95% CI, 52-83%) across both arms received the study intervention within 45 minutes of admission. There was some evidence of a difference in the proportion of participants with fibrinogen levels ≥ 2 g/L between arms (p = 0.10). Fibrinogen levels in the fibrinogen concentrate (FgC) arm rose by a mean of 0.9 g/L (SD, 0.5) compared with a reduction of 0.2 g/L (SD, 0.5) in the placebo arm and were significantly higher in the FgC arm (p < 0.0001) at 2 hours. Fibrinogen levels were not different at day 7. Transfusion use and thromboembolic events were similar between arms. All-cause mortality at 28 days was 35.5% (95% CI, 23.8-50.8%) overall, with no difference between arms. CONCLUSIONS: In this trial, early delivery of fibrinogen concentrate within 45 minutes of admission was not feasible. Although evidence points to a key role for fibrinogen in the treatment of major bleeding, researchers need to recognise the challenges of timely delivery in the emergency setting. Future studies must explore barriers to rapid fibrinogen therapy, focusing on methods to reduce time to randomisation, using 'off-the-shelf' fibrinogen therapies (such as extended shelf-life cryoprecipitate held in the emergency department or fibrinogen concentrates with very rapid reconstitution times) and limiting the need for coagulation test-based transfusion triggers. TRIAL REGISTRATION: ISRCTN67540073 . Registered on 5 August 2015

Barriers and facilitators to integrative oncology services in Australia : a changed mind set required

Objectives: This study aimed to explore barriers and facilitators to integrative oncology (IO) service provision and access in Australia. Design: The study design was mixed method with two substudies: a cross-sectional national cancer service survey of public and private sectors; and focus group interviews and an online survey of cancer survivors. Triangulation analysis of qualitative and quantitative data was used to identify and interrogate meta-themes. Subjects: The cancer service response rate was 93.2% (n = 275/295); 71/275 (25.8%) provided IO. Thirty three cancer survivors from Anglo-European, Arabic, Vietnamese, and Chinese backgrounds were interviewed, and 121 survivors answered the online survey. Results: IO gaps were substantial, with no services in many regions and cities; a lack of diversity and availability of therapeutic options, including culturally appropriate services; and a mismatch between the high use of natural health products by survivors and types of IO services provided. Two overlapping meta-themes were identified: ‘‘barriers and facilitators’’ and ‘‘peoples and institutions’’; each with four subthemes, respectively, ‘‘access/provision, affordability/funding, information/evidence, and culture/values’’ and ‘‘cancer survivors, healthcare professionals, organizations, and policies.’’ While affordability/funding was the greatest barrier to survivors and providers, solutions varied (e.g., building a stronger evidence-base, business model advice) and often conflicted (e.g., public verses private sector funding). The most insidious barrier was professional/corporate cultures and values that influenced hospital policies (or lack thereof), conceptions of evidence and the therapeutic alliance. Survivors called for a change of mindset in the culture of medicine and value-based health care. Conclusions: The barriers and facilitators to IO services were more complex than building the evidence-base and demonstrating value to justify funding. To achieve a better alignment of patients’ preferences with service provision, providers require more guidance on clinical governance, business models, local service gaps, and interprofessional collaboration. National strategies and funding models are needed to ensure appropriate, equitable IO service provision

Integrative Oncology in Australia 2016: Mapping Service Provision and Exploring Unmet Needs

AIM: to identify specialised cancer service provision across Australia and providers’ and cancer survivors’ views on important unmet needs, barriers and facilitators. Given the high use of Complementary Medicine (CM) by cancer survivors, the focus was Integrative Oncology (IO) where CM is integrated with conventional cancer healthcare. METHOD: NICM conducted a cross-sectional national survey of 295 public and private healthcare organisations with cancer services. One senior staff member from each eligible organisation was invited to answer a paper/online questionnaire. Concurrently, purposive sampling of cancer survivors from Arabic, Vietnamese, Chinese and Anglo-European Australian backgrounds was used to recruit 33 participants for four focus group interviews and 121 respondents for an on-line survey. Triangulation mixed method analysis synthesised the results from the quantitative and qualitative data. RESULTS: The national survey response rate was 93% (275/295), from which 71 (25%) provided IO services for a median duration of six years. IO was provided in a variety of settings - inpatient (52%), outpatient (53%), dedicated centre (35%) and home/residential care visits (4%). The Northern Territory was the only state/territory with no IO services. Compared to non-IO providers, organisations were more likely to be owned by a not-for-profit company (46%) or were government owned (38%) (p<0.001). Provision was restricted at most sites to a limited range of non-biologically based services, most commonly massage (73%), wellbeing (71%), and movement modalities (39%). Institutional policies and information regarding CM products and practitioner services were generally underdeveloped and inconsistent for IO and non-IO providers alike. The most important unmet need identified by providers was supportive care services, including IO. Cancer survivors emphasised that IO was not a ‘luxury item’, rather it was an important adjuvant for treatment side effects, co-morbidities, rehabilitation and quality of life. Four inter-related themes emerged – finance, logistics, information, and culture – as the barriers and facilitators to IO. The strongest convergence across the data was financial barriers. IO provision relied heavily upon patient payments, followed by philanthropy, and volunteer practitioners. Funding was the greatest barrier identified by 60% of non-IO providers. Out-of-pocket costs were a significant personal barrier to accessing CM or more CM. Views on funding solutions were more contentious. Other important barriers were lack of IO service provision, difficulties in referral pathways, healthcare professional attitudes, insufficient evidence, and uncertainty around patient demand, which services to provide and sustainable business models. CONCLUSION: Australian organisations are increasingly providing IO services, signalling the need for clearer national guidance and polices. Discrepancies continue between what cancer survivors are doing or seeking, and the IO services they can access. Survivorship and wellness clinics are in urgent need of development. Coordinated strategic planning between all providers and insurers is required if the long-term needs of cancer survivors are to be adequately and equitably met. COLLABORATION: NICM and the Centre for Health Research, Western Sydney University partnered with South West Sydney Local Health District and the registered charity, Oncology Massage Limited

Health-Related Quality of Life, Psychological Distress, and Sexual Changes Following Prostate Cancer:A Comparison of Gay and Bisexual Men With Heterosexual Men

AbstractIntroductionDecrements in health-related quality of life (HRQOL) and sexual difficulties are a recognized consequence of prostate cancer (PCa) treatment. However little is known about the experience of gay and bisexual (GB) men.AimHRQOL and psychosexual predictors of HRQOL were examined in GB and heterosexual men with PCa to inform targeted health information and support.MethodOne hundred twenty-four GB and 225 heterosexual men with PCa completed a range of validated psychosexual instruments.Main outcome measureFunctional Assessment of Cancer Therapy – Prostate (FACT-P) was used to measure HRQOL, with validated psychosexual measures, and demographic and treatment variables used as predictors.ResultsGB men were significantly younger (64.25 years) than heterosexual men (71.54 years), less likely to be in an ongoing relationship, and more likely to have casual sexual partners. Compared with age-matched population norms, participants in both groups reported significantly lower sexual functioning and HRQOL, increased psychological distress, disruptions to dyadic sexual communication, and lower masculine self-esteem, sexual confidence, and sexual intimacy. In comparison with heterosexual men, GB men reported significantly lower HRQOL (P = .046), masculine self-esteem (P < .001), and satisfaction with treatment (P = .013); higher psychological distress (P = .005), cancer related distress (P < .001) and ejaculatory concern (P < .001); and higher sexual functioning (P < .001) and sexual confidence (P = .001). In regression analysis, psychological distress, cancer-related distress, masculine self-esteem, and satisfaction with treatment were predictors of HRQOL for GB men (R2Adj = .804); psychological distress and sexual confidence were predictors for heterosexual men (R2Adj = .690).ConclusionThese findings confirm differences between GB and heterosexual men in the impact of PCa on HRQOL across a range of domains, suggesting there is a need for GB targeted PCa information and support, to address the concerns of this “hidden population” in PCa care