Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), against Neisseria gonorrhoeae infection in men who have sex with men: the GoGoVax study protocol.

INTRODUCTION: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae, has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis, may provide cross-protection against the closely related bacterium N. gonorrhoeae. This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+). METHODS AND ANALYSIS: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm3), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae-specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae-specific antibodies. ETHICS AND DISSEMINATION: Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04415424.

A proposal for a simplified measure of HIV preexposure prophylaxis prevention-effective adherence in self-report questionnaires.

Evaluating HIV preexposure prophylaxis (PrEP) use and HIV risk events concurrently remains challenging. We developed a single question method for measuring prevention-effective adherence with PrEP in self-report questionnaires. In a questionnaire completed by 409 gay and bisexual men, 46% reported condomless anal sex that was not covered by their own PrEP use, and this was more common among younger, lower-income participants. Refining this questionnaire item could improve measurement of prevention-effective adherence.

Attitudes Towards Treatment as Prevention Among PrEP-Experienced Gay and Bisexual Men in Australia.

The introduction of HIV pre-exposure prophylaxis (PrEP) has the potential to impact the attitudes gay and bisexual men (GBM) who consequently choose to take PrEP have towards treatment as prevention (TasP), and the extent to which they are willing to have condomless anal intercourse (CLAI) with an HIV-positive sexual partner who has an undetectable viral load (UVL). Using a cross-sectional sample from an observational cohort study conducted from August 2018 to March 2020, we examined the extent to which PrEP-experienced GBM are willing to have CLAI with a partner who has a UVL. Simple and multiple logistic regression models were used to identify associated variables. Of the 1386 participants included in the analyses, 79.0% believed in the effectiveness of TasP, and 55.3% were willing to have CLAI with a partner who has a UVL. Wiling participants were less worried about getting HIV when taking PrEP and more likely to believe in TasP. Further research is needed to better understand the gap between belief in TasP and willingness to have CLAI with a partner who has a UVL among PrEP-experienced GBM.

Identifying Patterns of Discontinuing and Recommencing Pre-exposure Prophylaxis in the Context of Sexual Behavior Among Gay and Bisexual Men in Australia.

We mapped gay and bisexual men's (GBM) patterns of using pre-exposure prophylaxis (PrEP) over time and explored sexual behavior as PrEP use changed. We conducted semi-structured interviews between June 2020 and February 2021 with 40 GBM living in Australia who had changed their PrEP use since initiating. There was considerable diversity in patterns of discontinuation, suspension, and recommencement of PrEP. Reasons for changing PrEP use mostly centered on accurate perceived changes to HIV risk. Twelve participants reported condomless anal intercourse with casual or fuckbuddy partners after discontinuing PrEP. These sex events were unanticipated, condoms were not a preferred option, and other risk reduction strategies were applied inconsistently. Service delivery and health promotion can support safer sex among GBM when PrEP use fluctuates by promoting event-driven PrEP and/or non-condom-based risk reduction methods during periods off daily PrEP, and guiding GBM to better recognize changing circumstances of risk and when to recommence PrEP.

Factors Associated With Willingness to Use Daily Antibiotics as Sexually Transmitted Infection Prophylaxis Among HIV Preexposure Prophylaxis-Experienced Gay and Bisexual Men in Australia.

BACKGROUND: Gay and bisexual men (GBM) who use HIV preexposure prophylaxis (HIV-PrEP) have high rates of bacterial sexually transmitted infections (STIs). The use of daily antibiotics as STI preexposure prophylaxis (STI-PrEP) may be appealing to GBM who are using or have previously used HIV-PrEP (HIV-PrEP-experienced) for the prevention of bacterial STIs. METHODS: We examined willingness to use daily STI-PrEP among a cross-sectional sample of HIV-PrEP-experienced GBM in Australia who participated in an observational online cohort study from August 2018 to March 2020. Factors associated with willingness to use daily STI-PrEP were determined using bivariate and multivariate logistic regression. RESULTS: Of the 1347 participants, half (54.3%) were willing to use daily STI-PrEP. Factors independently associated with greater willingness to use daily STI-PrEP included having >10 sexual partners in the last 6 months, using methamphetamine in the last 6 months, being more conscious about avoiding STIs, having a greater number of STIs since commencing HIV-PrEP, being willing to take HIV-PrEP for as long as they were at risk of acquiring HIV, and only using condoms when a sexual partner requested them. Conversely, factors associated with less willingness to use daily STI-PrEP included being university educated, using nondaily dosing regimens of HIV-PrEP, preferring event-driven HIV-PrEP, and being concerned about long-term HIV-PrEP adverse effects. CONCLUSIONS: Sexually transmitted infection PrEP is likely to be appealing to many HIV-PrEP-experienced GBM, especially those who engage in activities associated with a higher risk of STI transmission. However, they are less likely to be willing to use STI-PrEP unless it aligns with their HIV-PrEP dosing regimen, suggesting that research into the safety and efficacy of alternative STI prophylaxis dosing options should be prioritized.

Discontinuation of government subsidized HIV pre-exposure prophylaxis in Australia: a whole-of-population analysis of dispensing records.

INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) has been government subsidized in Australia since April 2018 and while uptake is high among men who have sex with men, rates of discontinuation are also high. The aims of this study were to examine the impact of discontinuation on overall PrEP usage, the proportion of PrEP users who discontinue and the predictors of discontinuation. METHODS: We used linked de-identified dispensing records of all government subsidized PrEP in Australia between April 2018 and September 2021: a whole-of-population data set. Defining discontinuation as 180 days or more without PrEP after the final dispensed supply, we calculated the number of people who discontinued at each 6-month interval during the study period, the proportion who had discontinued 2 years after the first supply and, using Cox regression, predictors of discontinuation. RESULTS: Of 49,164 people dispensed PrEP (98.5% male, median age 34 years), 40.3% (19,815) had discontinued by September 2021. Within 2 years of their first supply, 11,150 (37.7%) of 29,549 PrEP users had discontinued, including 10.0% after a single dispensed supply. Large variations were observed, particularly according to prescriber characteristics: discontinuation was higher among people prescribed PrEP by low caseload (≤10 patients) prescribers (61.2%) than by high caseload (>100 patients) prescribers (31.1%, p<0.001), and by prescribers practising in areas with low estimated prevalence (<1.0%) of gay men (64.1%) than high (>5%) prevalence (36.7%, p<0.001). Women and younger people were more likely to discontinue, while patients receiving a higher level of government subsidy were less likely. The independent predictors of discontinuation with the greatest effect size were female sex (adjusted hazards ratio [aHR] 2.99, p<0.001), low estimated gay prevalence of prescriber location (aHR 1.98, p<0.001) and low prescriber PrEP caseload (aHR 1.79, p<0.001). CONCLUSIONS: There are high rates of PrEP discontinuation in Australia and some populations are at increased risk of discontinuation. Strategies are needed to support persistence on PrEP and the re-starting of PrEP during periods of risk.

Sustaining sexual and reproductive health through COVID-19 pandemic restrictions: qualitative interviews with Australian clinicians.

BACKGROUND: The sexual and reproductive health care of people with HIV and those at risk of HIV has largely been delivered face-to-face in Australia. These services adapted to the coronavirus disease 2019 (COVID-19) pandemic with a commitment to continued care despite major impacts on existing models and processes. Limited attention has been paid to understanding the perspectives of the sexual and reproductive health care workforce in the research on COVID-19 adaptations. METHODS: Semi-structured interviews were conducted between June and September 2021 with 15 key informants representing a diverse range of service settings and professional roles in the Australian sexual and reproductive health sector. Inductive themes were generated through a process of reflexive thematic analysis, informed by our deductive interest in clinical adaptations. RESULTS: The major adaptations were: triage (rapidly adapting service models to protect the most essential forms of care); teamwork (working together to overcome ongoing threats to service quality and staff wellbeing), and the intwined themes of telehealth and trust (remaining connected to marginalised communities through remote care). Despite impacts on care models and client relationships, there were sustained benefits from the scaleup of remote care, and attention to service safety, teamwork and communication. CONCLUSIONS: Attending to the experiences of those who worked at the frontline of the COVID-19 response provides essential insights to inform sustained, meaningful system reform over time. The coming years will provide important evidence of longer-term impacts of COVID-19 interruptions on both the users and providers of sexual and reproductive health services.

Increased awareness of event-driven PrEP and knowledge of how to use it: results from a cross-sectional survey of gay and bisexual men in Australia.

BACKGROUND: Recent changes to Australian PrEP prescribing guidelines support the use of event-driven pre-exposure prophylaxis (ED-PrEP) to prevent HIV among gay and bisexual men (GBM). Social marketing campaigns to increase awareness of ED-PrEP were conducted in early 2021. This study aimed to assess the awareness and knowledge of this method after these campaigns. METHODS: We conducted a national cross-sectional online survey about PrEP knowledge and attitudes from March to May 2021. Participants were asked if they had heard of ED-PrEP. Among aware participants, questions about the '2-1-1' method were asked to assess knowledge. Bivariate and multivariate logistic regression analyses were conducted to assess the characteristics of those who were aware of ED-PrEP, and those who had correct knowledge of ED-PrEP. Analysis was restricted to non-HIV-positive cis-GBM who were aware of PrEP. RESULTS: Among the 419 participants eligible for this analysis, 286 (68.3%) had heard of ED-PrEP. Awareness was associated with living in a postcode with ≥10% gay men, PrEP experience, and belief ED-PrEP is effective. Of these 286 participants, 125 (43.7%) correctly answered questions about how to take ED-PrEP. Correct knowledge was associated with PrEP experience and belief ED-PrEP is effective. CONCLUSIONS: A growing proportion of GBM are aware of ED-PrEP, but many still do not know how to take it as per clinical guidelines. More work is needed to increase knowledge among GBM to promote effective use of this method.

Switching to Non-daily Pre-exposure Prophylaxis Among Gay and Bisexual Men in Australia: Implications for Improving Knowledge, Safety, and Uptake.

Introduction: Preexposure prophylaxis (PrEP) dosing options such as event-driven PrEP hold promise to increase PrEP uptake among gay, bisexual, and queer men (GBQM), but their impacts have not yet been realized and uptake by GBQM suitable for PrEP remains slow in countries where it is only considered an alternative option to daily PrEP. Methods: We conducted semi-structured interviews between June 2020 and February 2021 with 40 GBQM in Australia to understand PrEP dosing behaviors, knowledge, and preferences. Results: All participants commenced PrEP daily; 35% had ever switched to non-daily PrEP, mostly taking it event-driven. GBQM who preferred non-daily PrEP had infrequent or predictable sex, were concerned about cost given infrequency of sex, and/or wanted to minimize unnecessary drug exposure. Accurate knowledge of event-driven PrEP was poor. However, reflecting concepts underpinning critical pedagogy, having accurate knowledge was supported by access to consistent messaging across clinical, social, community, and public settings. Several participants who switched to event-driven PrEP had condomless sex events in which they were unable to adhere to pills due to unanticipated sex. Conclusions and Policy Implications: Implementation of comprehensive and consistent education about correct dosing for event-driven PrEP across multiple settings is needed to ensure increased uptake and safe use. GBQM require messaging about non-condom based HIV prevention strategies when they cannot access daily or event-driven PrEP.

Incorrect Knowledge of Event-Driven PrEP "2-1-1" Dosing Regimen Among PrEP-Experienced Gay and Bisexual Men in Australia.

BACKGROUND: Event-driven pre-exposure prophylaxis (ED-PrEP), when taken according to the "2-1-1" dosing method, is highly effective at preventing HIV acquisition for gay, bisexual, and other men who have sex with men (GBM). Any missed doses when using ED-PrEP drastically reduce its effectiveness, so it is vital that people using this method know how to take it correctly. This study investigated Australian GBM's awareness of ED-PrEP and their knowledge of how to take it correctly. METHOD: We conducted a survey of 1471 PrEP-experienced GBM in Australia, between October 2019 and March 2020. The survey assessed awareness and knowledge of the 3 components of the "2-1-1" ED-PrEP dosing regimen (number of pills for loading dose, timing of loading dose, and number of days after sex to take PrEP pills) among GBM. Characteristics associated with ED-PrEP awareness and correct knowledge of how to take ED-PrEP were assessed with multivariate logistic regression. RESULTS: Two-thirds (n = 1004, 68.4%) had heard of ED-PrEP, of whom only one-eighth (n = 125, 12.5%) knew the correct details of the "2-1-1" ED-PrEP method; one-third (n = 339, 33.8%) did not know any of the 3 key components. Awareness of ED-PrEP and correct knowledge was associated with greater belief in PrEP efficacy, university education, and intention to take a nondaily PrEP regimen in the next 6 months. CONCLUSIONS: Although ED-PrEP awareness was considerable, most participants did not know how to use ED-PrEP correctly. Further work is needed to increase awareness and knowledge of ED-PrEP among GBM.

Preferences for Current and Future PrEP Modalities Among PrEP-Experienced Gay and Bisexual Men in Australia.

Alternatives to daily dosing of HIV pre-exposure prophylaxis (PrEP) are continuing to emerge. From October 2019 to March 2020, we conducted an online survey of PrEP-experienced gay and bisexual men in Australia about interest in and preference for four different PrEP modalities: daily dosing, event-driven dosing, long-acting injectable (LAI)-PrEP and subdermal PrEP implants. Using data from 1477 participants, we measured interest and preference of different modalities using multivariate logistic regression. High proportions of participants were interested in LAI-PrEP (59.7%), daily PrEP (52.0%), PrEP implants (45.3%) and event-driven PrEP (42.8%). LAI-PrEP was the most frequently selected preference (30.5%), followed by PrEP implants (26.3%), daily PrEP (21.4%) and event-driven PrEP (21.2%). Higher interest and preference for non-daily PrEP modalities were associated with being concerned about side effects and perceived difficulties with daily adherence. As novel modalities emerge, attitudes to them should be considered in public health messaging to facilitate informed decision-making.

A Pragmatic Randomized Comparative Trial of e-Cigarettes and Other Nicotine Products for Quitting or Long-Term Substitution in Smokers.

INTRODUCTION: Tobacco harm reduction has potential to improve individual and population health. However, little research exists on low-intensity interventions, such as encouraging longer-term NRT or e-cigarette use. We aimed to determine whether: (1) encouraging use of nicotine products as long-term tobacco substitutes is more effective for smoking abstinence than standard treatment, and (2) offering e-cigarettes is more effective than NRT. METHODS: An open-label, parallel-group randomized trial was conducted in Australia between 2014 and 2015, with 1563 adult daily smokers, randomized to: (A) standard cessation advice and NRT: advice to use NRT short-term, (B) quit or substitute advice and NRT: advice to use NRT as a longer-term substitute for smoking if required to maintain smoking cessation, or (C) Quit or substitute advice and NRT and/or e-cigarettes. Participants were offered an initial supply of products they could then purchase for up to 7 months. The primary outcome was self-reported continuous smoking abstinence at 7 months. Point prevalence, dual use, and cigarette reduction were secondary outcomes. RESULTS: At 7 months, 2.8% (N = 9) of group A (N = 324) were abstinent, compared with 1.8% (N = 11) in B (N = 620) and 1.3% (N = 8) in C (N = 619) (adjusted odds ratio [ORs]: B vs. A 0.66, 95% confidence interval [CI]: 0.27-1.63; C vs. A 0.46, 95% CI: 0.17-1.21; C vs. B 0.69, 95% CI 0.27-1.73). There were no suspected unexpected serious adverse reactions associated with trial products. CONCLUSION: A free trial of NRT and first generation e-cigarettes and advice on long-term substitution was no better for smoking abstinence than usual care. CLINICAL TRIAL REGISTRATION: The trial was registered with the Australian Therapeutic Goods Administration under their Clinical Trials Notification scheme and the Australian and New Zealand Clinical Trials Registry (ACTRN12612001210864). IMPLICATIONS: This pragmatic trial allowed the comparison of existing and alternative policy options under semi-realistic conditions, such as product choice and financial cost. All trial arms had low rates of smoking cessation. The findings suggest that providing unflavored cigalike e-cigarettes without additional support may not increase quitting compared with advice to use standard NRT in a general population of Australians who smoke. More intensive support and education, and/or opportunity to try a range of e-cigarette products, may be required to motivate quit attempts using e-cigarettes.

Overcoming barriers to HIV pre-exposure prophylaxis (PrEP) coverage in Australia among Medicare-ineligible people at risk of HIV: results from the MI-EPIC clinical trial.

Background Overseas-born people who are ineligible for government-subsidised health care experience barriers to accessing HIV pre-exposure prophylaxis (PrEP) in Australia. This study aimed to assess a program providing free PrEP to overseas-born adults at risk of acquiring HIV. Methods Medicare-Ineligible Expanded Implementation in Communities (MI-EPIC) was a single-arm, open-label trial of daily tenofovir disoproxil fumarate/emtricitabine as PrEP. Six clinics recruited Medicare-ineligible adults who met HIV risk criteria in New South Wales, Australia. We recorded data on HIV and sexually transmitted infection (STI) diagnoses, and PrEP dispensing from July 2019 to June 2020. PrEP adherence as a medication possession ratio (MPR) was calculated as pills dispensed divided by days. We administered an optional survey on behaviours and attitudes to PrEP and sexual health. Results The 221 participants (206 men; 93.2%) had a median age of 29years (IQR 26-34). Participants were mostly born in Asia (53.4%), Latin America or the Caribbean (25.3%), or Europe (10.9%). Adherence was high; 190 participants (86.0%) had an MPR of >60%. Of 121 survey participants, 42 (34.7%) completed the survey in a language other than English. Of participants who had not used PrEP in the 6months before enrolment (n=45, 37.2%), the most common reasons were cost (n=22, 48.9%), and lack of knowledge about accessing PrEP (n=20, 44.4%). Conclusions Medicare-ineligible people at risk of HIV demonstrate high adherence when given access to free PrEP and translated information. Increasing PrEP awareness and reducing barriers to accessing PrEP in this high-risk population should be priorities in HIV prevention.

ACTIVATION (PercutAneous Coronary inTervention prIor to transcatheter aortic VAlve implantaTION): A Randomized Clinical Trial.

OBJECTIVES: This study sought to determine if percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) in patients with significant coronary artery disease would produce noninferior clinical results when compared with no PCI (control arm). BACKGROUND: PCI in patients undergoing TAVR is not without risk, and there are no randomized data to inform clinical practice. METHODS: Patients with severe symptomatic aortic stenosis and significant coronary artery disease with Canadian Cardiovascular Society class ≤2 angina were randomly assigned to receive PCI or no PCI prior to TAVR. The primary endpoint was a composite of all-cause death or rehospitalization at 1 year. Noninferiority testing (prespecified margin of 7.5%) was performed in the intention-to-treat population. RESULTS: At 17 centers, 235 patients underwent randomization. At 1 year, the primary composite endpoint occurred in 48 (41.5%) of the PCI arm and 47 (44.0%) of the no-PCI arm. The requirement for noninferiority was not met (difference: -2.5%; 1-sided upper 95% confidence limit: 8.5%; 1-sided noninferiority test P = 0.067). On analysis of the as-treated population, the difference was -3.7% (1-sided upper 95% confidence limit: 7.5%; P = 0.050). Mortality was 16 (13.4%) in the PCI arm and 14 (12.1%) in the no-PCI arm. At 1 year, there was no evidence of a difference in the rates of stroke, myocardial infarction, or acute kidney injury, with higher rates of any bleed in the PCI arm (P = 0.021). CONCLUSIONS: Observed rates of death and rehospitalization at 1 year were similar between PCI and no PCI prior to TAVR; however, the noninferiority margin was not met, and PCI resulted in a higher incidence of bleeding. (Assessing the Effects of Stenting in Significant Coronary Artery Disease Prior to Transcatheter Aortic Valve Implantation; ISRCTN75836930).

Radial Artery Occlusion After Transradial Interventions: A Systematic Review and Meta-Analysis.

BACKGROUND: Radial artery occlusion (RAO) may occur posttransradial intervention and limits the radial artery as a future access site, thus precluding its use as an arterial conduit. In this study, we investigate the incidence and factors influencing the RAO in the current literature. METHODS AND RESULTS: We searched MEDLINE and EMBASE for studies of RAO in transradial access. Relevant studies were identified and data were extracted. Data were synthesized by meta-analysis, quantitative pooling, graphical representation, or by narrative synthesis. A total of 66 studies with 31 345 participants were included in the analysis. Incident RAO ranged between <1% and 33% and varied with timing of assessment of radial artery patency (incidence of RAO within 24 hours was 7.7%, which decreased to 5.5% at >1 week follow-up). The most efficacious measure in reducing RAO was higher dose of heparin, because lower doses of heparin were associated with increased RAO (risk ratio 0.36, 95% CI 0.17-0.76), whereas shorter compression times also reduced RAO (risk ratio 0.28, 95% CI 0.05-1.50). Several factors were found to be associated with RAO including age, sex, sheath size, and diameter of radial artery, but these factors were not consistent across all studies. CONCLUSIONS: RAO is a common complication of transradial access. Maintenance of radial patency should be an integral part of all procedures undertaken through the radial approach. High-dose heparin along with shorter compression times and patent hemostasis is recommended in reducing RAO.

Assessing the place of neurobiological explanations in accounts of a family member's addiction.

INTRODUCTION AND AIMS: The brain disease model of addiction posits that addiction is a persistent form of neural dysfunction produced by chronic drug use, which makes it difficult for addicted persons to become and remain abstinent. As part of an anticipatory policy analysis of addiction neuroscience, we engaged family members of addicted individuals to assess their views on the place and utility of brain-based accounts of addiction. DESIGN AND METHODS: Fifteen in-depth qualitative interviews were conducted and used to develop a quantitative online survey that was completed by 55 family members. This article reports responses on what addiction is and how it is caused and responses to explanations of the brain disease model of addiction. RESULTS: Participants gave multiple reasons for their family members developing an addiction and there was no single dominant belief about the best way to describe addiction. Participants emphasised the importance of both scientific and non-scientific perspectives on addiction by providing multifactorial explanations of their family members' addictions. Most family members acknowledged that repeated drug use can cause changes to the brain, but they varied in their reactions to labelling addiction a 'brain disease'. They believed that understanding addiction, and how it is caused, could help them support their addicted relative. DISCUSSION AND CONCLUSIONS: Participants' beliefs about neurobiological information and the brain disease model of addiction appeared to be driven by empathetic, utilitarian considerations rather than rationalist ones. We discuss the importance of providing information about the nature and causes of addiction. [Meurk C, Fraser D, Weier M, Lucke J, Carter A, Hall W. Assessing the place of neurobiological explanations in accounts of a family member's addiction. Drug Alcohol Rev 2016;35:461-469].

Protocol for a randomised pragmatic policy trial of nicotine products for quitting or long-term substitution in smokers.

BACKGROUND: Smoking is Australia's leading preventable cause of premature mortality and a major contributor to the national disease burden. If quit rates do not dramatically improve, then smoking will continue to be a major public health issue for decades to come. Harm-reduction approaches using novel nicotine products like e-cigarettes as long term replacements for smoking have the potential to improve quit rates. However, little research has assessed such approaches. DESIGN: Three-arm parallel-group pragmatic randomised controlled trial. PARTICIPANTS: People living in Australia who are at least 18 years old, smoke five or more cigarettes per day and are willing to try a sample of nicotine products. INTERVENTION: Participants are randomised to receive standard quit advice and medicinal nicotine (Condition A); quit or substitute advice and medicinal nicotine (Condition B); or quit or substitute advice and medicinal nicotine and e-cigarettes (Condition C). Participants choose which (if any) nicotine products to receive to try in a free sample pack followed by a two to three week free supply of their favourite product(s) and the option to purchase more at a discounted price. Follow-up surveys will assess nicotine product use and smoking. PRIMARY OUTCOME: Continuous abstinence for at least 6 months. Target sample size: 1600 people (Condition A: 340; Condition B: 630; Condition C: 630) provides at least 80 % power at p = 0.05 to detect a 5 % difference in abstinence rates between each condition. DISCUSSION: This trial will provide data on tobacco harm-reduction approaches and in particular the use of e-cigarettes as a replacement for smoking. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12612001210864. Date of registration: 15/11/2012.

Intra-arterial vasodilators to prevent radial artery spasm: a systematic review and pooled analysis of clinical studies.

OBJECTIVES: The aim of this study is to review the available literature on the efficacy and safety of agents used for prevention of RAS. BACKGROUND: Different vasodilator agents have been used to prevent radial artery spasm (RAS) in patients undergoing transradial cardiac catheterization. METHODS: We included studies that evaluated any intra-arterial drug administered in the setting cardiac catheterization that was undertaken through the transradial access site (TRA). We also compared studies for secondary outcomes of major bleeding, procedure time, and procedure failure rate in setting of RAS prevention, patent hemostasis and radial artery occlusion. RESULTS: 22 clinical studies met the inclusion criteria. For placebo, RAS rate was 12% (4 studies, 638 participants), which was similar to 2.5mg of verapamil 12% (3 studies, 768 participants) but greater than 5mg of verapamil (4%, 2 studies, 497 participants). For nicorandil, there was a much higher RAS rate compared to placebo (16%, 3 studies, 447 participants). The lowest rates of RAS was found for nitroglycerin at both 100 µg (4%) and 200 µg (2%) doses, isosorbide mononitrate (4%) and nicardipine (3%). We found no information regarding the procedure failure rates, patent hemostasis, and radial artery occlusion in these studies. CONCLUSIONS: In this largest and up-to-date review on intra-arterial vasodilators use to reduce RAS, we have found that the verapamil at a dose of 5mg or verapamil in combination with nitroglycerine are the best combinations to reduce RAS.

Transradial intervention in ST elevation myocardial infarction.

Primary percutaneous coronary intervention (PPCI) in ST elevation myocardial infarction (STEMI) represents the current gold standard reperfusion therapy. Recent advances in antiplatelet and anticoagulant therapy have reduced the risk of ischemic complications and mortality in PPCI although this has been at the expense of major bleeding complications. Access site-related bleeding complications account for up to 50 % of major peri-procedural bleeding complications in PCI. Increasing adoption of the radial artery as the default access site has been shown to markedly reduce such major bleeding complications and mortality in selected patient cohorts. Recent data has suggested that adoption of the transradial access site in STEMI PCI procedures is associated with significant reductions in major bleeding complications and mortality in both national registry data and randomised controlled trials. We provide an overview of this data and discuss the remaining uncertainties around the synergy between access site and contemporary antithrombotic and antiplatelet therapy in such patients. Finally, whilst adoption of the radial artery as the default access site in PPCI has yielded a similar reduction in mortality as observed in the switch from thrombolysis to PPCI in the past, its adoption as a default access site is not universal. We discuss the remaining obstacles and challenges for more widespread adoption of the radial access site as the default access site in PPCI.

Vapers' perspectives on electronic cigarette regulation in Australia.

BACKGROUND: The use of electronic cigarettes (e-cigarettes), also known as personal vaporisers (PVs), has increased rapidly in Australia despite legal barriers to the sale, possession and use of nicotine for non-therapeutic purposes. Australia is one of many countries in the process of developing regulations for these devices yet knowledge of consumers' views on e-cigarette regulation is lacking. METHODS: An online survey was completed by 705 e-cigarette users recruited online. Participants answered questions about their smoking history, e-cigarette use, as well as their opinions on appropriate regulation of e-cigarettes. RESULTS: Most participants were male (71%), employed (72%), and highly educated (68% held post-school qualification). They tended to be former heavy smokers who had stopped smoking entirely and were currently vaping. Participants generally agreed that the government should enforce minimum labelling and packaging standards and there was majority support for minimum quality standards. Most supported making e-cigarettes available for sale to anyone over the age of 18, but expressed concern about the government's motivation for regulating e-cigarettes. There was strong opposition to restricting sales to a medicines framework (prescription only or pharmacy only sales). CONCLUSION: E-cigarette users in Australia are in favour of e-cigarettes being regulated as long as those regulations do not impede their ability to obtain devices and refill solutions, which they view as important for them to remain smoke free. These views align with some aspects of appropriate policy designed to maximise the public health potential of e-cigarettes in society, but conflict with some of the proposed regulatory models. Governments should consider how future regulation of e-cigarettes will affect current consumers while helping to maximise the number of smokers who switch to e-cigarettes and minimise the possibility of non-smokers becoming addicted to nicotine.