SummaryBackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91–1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

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Background Tranexamic acid safely reduces mortality in traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury and can cause brain herniation and death. We assessed the effects of tranexamic acid in traumatic brain injury patients. Objective To assess the effects of tranexamic acid on death, disability and vascular occlusive events in traumatic brain injury patients. We also assessed cost-effectiveness. Design Randomised trial and economic evaluation. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers and those assessing outcomes were masked to allocation. All analyses were by intention to treat. We assessed the cost-effectiveness of tranexamic acid versus no treatment from a UK NHS perspective using the trial results and a Markov model. Setting 175 hospitals in 29 countries. Participants Adults with traumatic brain injury within 3 hours of injury with a Glasgow Coma Scale score of ≤ 12 or any intracranial bleeding on computerised tomography scan, and no major extracranial bleeding, were eligible. Intervention Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo. Main outcome measures Head injury death in hospital within 28 days of injury in patients treated within 3 hours of injury. Secondary outcomes were early head injury deaths, all-cause and cause-specific mortality, disability, vascular occlusive events, seizures, complications and adverse events. Results Among patients treated within 3 hours of injury (n = 9127), the risk of head injury death was 18.5% in the tranexamic acid group versus 19.8% in the placebo group (855/4613 vs. 892/4514; risk ratio 0.94, 95% confidence interval 0.86 to 1.02). In a prespecified analysis excluding patients with a Glasgow Coma Scale score of 3 or bilateral unreactive pupils at baseline, the results were 12.5% in the tranexamic acid group versus 14.0% in the placebo group (485/3880 vs. 525/3757; risk ratio 0.89, 95% confidence interval 0.80 to 1.00). There was a reduction in the risk of head injury death with tranexamic acid in those with mild to moderate head injury (166/2846 vs. 207/2769; risk ratio 0.78, 95% confidence interval 0.64 to 0.95), but in those with severe head injury (689/1739 vs. 685/1710; risk ratio 0.99, 95% confidence interval 0.91 to 1.07) there was no apparent reduction (p-value for heterogeneity = 0.030). Early treatment was more effective in mild and moderate head injury (p = 0.005), but there was no obvious impact of time to treatment in cases of severe head injury (p = 0.73). The risk of disability, vascular occlusive events and seizures was similar in both groups. Tranexamic acid is highly cost-effective for mild and moderate traumatic brain injury (base case of £4288 per quality-adjusted life-year gained). Conclusion Early tranexamic acid treatment reduces head injury deaths. Treatment is cost-effective for patients with mild or moderate traumatic brain injury, or those with both pupils reactive. Future work Further trials should examine early tranexamic acid treatment in mild head injury. Research on alternative routes of administration is needed. Limitations Time to treatment may have been underestimated. Trial registration Current Controlled Trials ISRCTN15088122, ClinicalTrials.gov NCT01402882, EudraCT 2011-003669-14, Pan African Clinical Trial Registry PACTR20121000441277. Funding The project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 26. See the NIHR Journals Library website for further project information. In addition, funding was provided by JP Moulton Charitable Trust, Joint Global Health Trials (Medical Research Council, Department for International Development and the Wellcome Trust). This project was funded by the NIHR Global Health Trials programme.

The People Living with HIV StigmaSurvey UK 2015 was a community led national survey investigating experiences of people living with HIV in the UK in the past 12 months. Participants aged 18 and over were recruited through over 120 cross-sector community organisations and 46 HIV clinics to complete an anonymous online survey. Trans is an umbrella term which refers to individuals whose current gender identity is different to the gender they were assigned at birth. Trans participants self-identified via gender identity and gender at birth questions. Descriptive analyses of reported experiences in social and health care settings were conducted and multivariate logistic regression analyses were used to identify sociodemographic predictors of reporting being treated differently to non-HIV patients, and being delayed or refused healthcare treatment in the past 12 months. 31 out of 1576 participants (2%) identified as trans (19 trans women, 5 trans men, 2 gender queer/non-binary, 5 other). High levels of social stigma were reported for all participants, with trans participants significantly more likely to report worrying about verbal harassment (39% vs. 23%), and exclusion from family gatherings (23% vs. 9%) in the last 12 months, compared to cisgender participants. Furthermore, 10% of trans participants reported physical assault in the last 12 months, compared to 4% of cisgender participants. Identifying as trans was a predictor of reporting being treated differently to non-HIV patients (48% vs. 30%; aOR 2.61, CI 1.06, 6.42) and being delayed or refused healthcare (41% vs. 16%; aOR 4.58, CI 1.83, 11.44). Trans people living with HIV in the UK experience high levels of stigma and discrimination, including within healthcare settings, which is likely to impact upon health outcomes. Trans-specific education and awareness within healthcare settings could help to improve service provision for this demographic.

Background Black and minority ethnic (BME) men who have sex with men (MSM) face a major burden in relation to HIV infection. Using a cross-sectional correlational survey design, the present study explored the relationships between HIV knowledge and reported sexual health and sexual behaviour in this population. Methods: A convenience sample of 538 BME MSM was recruited in London, Leicester and Leeds: 346 (64%) self-identified as South Asian, 88 (16%) self-identified as Latin American, 76 (14%) self-identified as Black, 13 (2%) self-identified as mixed, and 15 (3%) self-identified as other. Results: HIV knowledge was low across the board, and South Asian MSM manifested the lowest scores. Respondents who perceived their HIV risk to be low possessed the least HIV knowledge. There were interethnic differences in the frequency of gay sauna visits, sex-seeking on mobile applications, drug use and attendance at sex parties. Respondents reported a high frequency of racism and discrimination, with Black MSM reporting highest frequency. Conclusions: There is an urgent need to raise awareness of HIV in BME MSM, and a culturally competent approach to HIV awareness-raising in BME MSM is required. These findings shed light on the contexts in which HIV prevention efforts should be targeted to reach specific ethnic groups, as well as some of the potential syndemics that can increase HIV risk or undermine HIV outcomes in BME MSM patients.