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Academic EM blog number 5: Prof Jason Smith

3/7/2020

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​I thought it prudent to give another academic update, given that there has been some big research news in terms of COVID-19 and other relevant emergency medicine studies in the last couple of weeks.  If you want a general update on the state of play nationally with regards to emergency medicine research, some of the challenges we’ve faced and how the future might look, check out this recent podcast which is available via the RCEM Learning site:
http://iz4.me/VO8s6zO8eBb1
 
COVID-19 research
 
I’ve mentioned the RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial before. This is a large UK multicentre randomised controlled trial, led by researchers in Oxford, of possible treatments for patients admitted to hospital with COVID-19. Many of us have recruited patients to this study, which is still ongoing. As a reminder, the treatment arms are:
 
  • Lopinavir-Ritonavir (commonly used to treat HIV)
  • Low-dose Dexamethasone 
  • Hydroxychloroquine (which has now been stopped due to lack of efficacy)
  • Azithromycin 
  • Tocilizumab (an anti-inflammatory treatment given by injection)
  • Convalescent plasma (containing antibodies against the SARS-CoV-2 virus, collected from donors who have recovered from COVID-19)
 
It has an unusual and novel adaptive design – so it changes as time goes on, and tests multiple interventions, with the ability to stop or start different treatments as the trial progresses. It makes traditional methodologists twitch. Outcome is all cause mortality at 28 days. 
 
The first result published was hydroxychloroquine – which showed no benefit – and so that arm was discontinued. The second result, which resulted in a press release last week, was the dexamethasone arm. The pre-print of the full results paper is now available at:
https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1
They found that dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), and by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002). Impressive stuff from the UK medical research community, and a further illustration that academia is the new rock and roll.
 
Non-COVID evidence
 
More big news from an emergency medicine study that spanned half a decade in our emergency departments across the UK and indeed the world. Should we give TXA to patients with GI bleeds? 
 
The results of the HALT-IT study have now been published:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30848-5/fulltext
The trial found that tranexamic acid does not reduce deaths from GI bleeding (mortality was 4% in both the intervention and control groups). Of note, it increased the risk of venous thromboembolic events (deep vein thrombosis or pulmonary embolism), although the absolute risk was low (0.8% versus 0.4%). Re-bleeding was similar in both groups. 
So, an intervention that had crept into routine practice in my hospital, certainly among the admitting physicians looking after these patients because it felt like the right thing to do, is torpedoed by robust clinical evidence from a randomised controlled trial. 
 
 
Stay safe and sane,
Jason Smith on behalf of the academic team
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