RCEM COVID-19 CPD
Top 5 papers: Week 9

Authors: Dr Govind Oliver, Dr Anisa Jafar, Dr Daniel Derbyshire, Professor Simon Carley and the RCEM COVID-19 CPD team / Editor: Govind Oliver / Codes: CAP6, CAP9, CC16, HAP29, HAP6 / Published: 09/07/2020

Another week, another top 5! The volume and quality of evidence continues to grow with the team screening over 1,500 studies. This week’s top 5 contains policy shaping big hitters and an additional +1 follow up piece with a spark of controversy. If these don’t satisfy your appetite, then check out the Directors Cut for 10 more that caught our eye. If you would prefer an interactive live journal club, then keep an eye on social media for confirmation of when the next one will be.

The following papers have been split into 3 categories that will allow you to focus on those that are most vital to your practice.

  • Worth a peek: interesting, but not yet ready for prime time
  • Head Turner: new concepts
  • Game Changer: this paper should change practice

Game changer summary:

Beigel et al. report a reduction in the time to recovery with remdesivir.1

Peccia et al. show that sewage sludge could help pre-empt peaks in COVID-19 cases.2

Watson et al.6 outline concerns about the data integrity of the analysis by Mehra et al.7

Summary of the rest:

Hall et al. describe the disruption to MedEd and provide tips to combat these.3

Marijon et al. explore the impact of COVID-19 on out-of-hospital cardiac arrests.4

Eboni et al. emphasise the role of socio-demographics in the pandemics observed.5

Remdesivir for the Treatment of Covid-19 – Preliminary Report by Beigel et al.1

Topic: Treatment

Rating: Game Changer

Scout: Dr Anisa Jafar

It’s Remdesivir again. Here is a 10 country, 73 site/sub-site double-blind randomised, placebo-controlled trial involving 1,063 hospitalised adults with COVID-19 and lower respiratory tract involvement entered in a 1:1 ratio. The key headline is improvement in the median time to recovery with remdesivir from 15 to 11 days. The good: the groups are reasonably well-matched (except placebo did have some more of the sicker patients who also then turned out to do less well on remdesivir). The bad: some sites used normal saline as placebo; there were some significant changes to the study protocol and we only know 14-day mortality figures. The ugly: around 25% appear to have disappeared from the analysis for some reason; the ordinal scale of severity categorisation needs close reading; and the sickest patients don’t seem to benefit. Game changer? In the current climate of lab-bench to headline news at break-neck speed: inevitably, as it’s a positive (although limited) result. As scientific stories go, we might be beyond the preface but this does still feel like Chapter 1.

SARS-CoV-2 RNA concentrations in primary municipal sewage sludge as a leading indicator of COVID-19 outbreak dynamics by Peccia et al.2

Topic: Epidemiology

Rating: Game changer

Scout: Professor Simon Carley

We have known for some time that the SARS-CoV-2 virus can be found in the gastrointestinal tract and in faeces. This paper looked for the presence of the virus in sewage sludge and found a rise in levels roughly a week before a peak in clinical cases. If this is reproducible it represents a step change in how we might manage the pandemic as we might be able to predict clinical activity with a 7-day preparation phase. This could be a real game changer. The caveats are that it is pre-print and single centre, but even so this may be a remarkable insight into how modern epidemiology might tackle the virus. I also love this as it arguably has a strong link to the birth of public health and epidemiology, the Broad Street cholera outbreak. Water and sewage should never be underestimated in public health matters.

Training disrupted: Practical tips for supporting competency-based medical education during the COVID-19 pandemic by Hall et al.3

Topic: Education

Rating: Worth a peek

Scout: Dr Daniel Darbyshire

Hall et al. use the term ‘disrupted’ to describe the changes that have occurred to the learning environment during COVID-19. Teaching, learning and assessment have not stopped – the paper offers the authors practical tips for supporting competency-based medical education during the disruption and is useful for all of us involved in education in its myriad of guises. All twelve tips are worth reviewing, we will summarise a selection here. Learners will need support beyond the skillset of their educators. This is fine. There is support and knowing what is out there locally for your trainees to access will make supporting them when (definitely when, not if) they need help. Aside the important content, face-to-face education has always had an important second role. Replicating the social bonding in an on-line or socially distanced setting is a real challenge. We need to prepare for the ‘post pandemic catch-up’ and anticipate the needs of learners who stay in or move to our departments. Listen to the learners, they will tell you what they need but you might need to innovate to help them do this.

Out-of-hospital cardiac arrest during the COVID-19 pandemic in Paris, France: a population-based, observational study by Marijon et al.4

Topic: Observational

Rating: Worth a peek

Scout: Dr Govind Oliver

What impact has the pandemic had in cardiac arrest care out-of-hospital? This observational study used the Paris Fire Brigade database and associated in-hospital data to compare a 6-week pandemic period with the same period in previous years. As one would expect, they saw an increase in the maximum weekly incidence of out-of-hospital cardiac arrest (OHCA) from 13.4 to 26.6 per million inhabitants in the pandemic. A higher number of OHCA occurred at home (90.2% vs. 76.8%), less received bystander CPR (47.8% vs. 63.9%) and there were slightly longer delays to intervention from 9.4 to 10.4 minutes. Interestingly, they noted a reduction in the number of patients being admitted alive (12.8% from 22.8%) and the number of patients with a shockable rhythm (9.2% from 19.1%). OHCA are up but the why is not clear from this study; to what extent are these changes directly related to COVID-19 compared to indirect effects from the lockdown.

Hospitalization and Mortality among Black Patients and White Patients with Covid-19 by Eboni et al.5

Topic: Prognosis

Rating: Worth a peek

Scout: Dr Anisa Jafa

In many respects, COVID-19 has become a herald and hallmark for drawing the world’s gaze firmly to the chasm of societal inequality and this study throws its weight behind this. It is a retrospective cohort study from Louisiana including 3,626 COVID-19 positive patients. Their multivariable analysis suggests that black race, older age, greater illness burden, public insurance, low-income residence and obesity increased likelihood of admission to hospital. When it came to mortality of hospitalised patients, age and other physiological/laboratory features were predictive; however black race was not an independent risk factor. The suggestion here is very much that the socio-demographics (and along with that of course, its impact on comorbidities) are the key to such a striking impact of COVID-19 on a specific racial group. It is one study, in one location with a specific population, it should not, however, be ignored.

An open letter to Mehra et al. and The Lancet. by Watson et al.6 in response to Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis by Mehra et al.7

Topic: Treatment

Rating: Game Changer (for the wrong reasons)

Scout: Dr Daniel Darbyshire

The astute amongst you will realise that Mehra et al. was presented in last weeks top 5. A quick precis: from the patient records of 96,032 hospitalised COVID-19 patients from six continents, use of either chloroquine or hydroxychloroquine was associated with an increase in in-hospital mortality and ventricular arrhythmias. The impact? The WHO is one of several regulatory bodies that have paused recruitment of patients into the hydroxychloroquine arm of active trials. The controversy? Over 140 leading scientists, researchers and statisticians have written an open letter outlining profound concerns about the integrity of the results with reasons including inadequate adjustment for known and measured confounding factors, data inconsistencies and the absence of any ethics review for the study. It called for the release of patient data for external validation amongst other things. The Lancet has now promised to conduct their own independent review of the data. Watch this space.

RCEM CPD COVID-19 TEAM

  • Dr Charles Reynard, NIHR Doctoral Research Fellow, University of Manchester
  • Dr Anisa Jafar, NIHR Clinical Lecturer, University of Manchester
  • Dr Govind Oliver, TERN & RCEM Learning editor, Preston
  • Dr Mina Naguib, NIHR Academic Clinical Fellow, Manchester
  • Dr Patricia van den Berg, NIHR Academic Clinical Fellow, Manchester
  • Dr Tom Roberts, RCEM Trainee Emergency Research Network Fellow, Bristol
  • Professor Pamela Vallely, Medical Virologist, University of Manchester
  • Professor Richard Body, Consultant in EM, University of Manchester
  • Professor Daniel Horner, Consultant in EM and ICU, Salford
  • Professor Simon Carley, Consultant in EM, RCEM CPD Lead

References

  1. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 – Preliminary Report [published online ahead of print, 2020 May 22]. N Engl J Med 2020;10.1056/NEJMoa2007764. doi:10.1056/NEJMoa2007764
  2. Peccia J, Zulli A, Brackney DE, et al. SARS-CoV-2 RNA concentrations in primary municipal sewage sludge as a leading indicator of COVID-19 outbreak dynamics. medRxiv 2020.05.19.20105999; doi: https://doi.org/10.1101/2020.05.19.20105999
  3. Hall AK, Nousiainen MT, Campisi P, et al. Training disrupted: Practical tips for supporting competency-based medical education during the COVID-19 pandemic [published online ahead of print, 2020 May 25]. Med Teach. 2020;1-6. doi:10.1080/0142159X.2020.1766669
  4. Marijon E, Karam N, Jost D, et al. Out-of-hospital cardiac arrest during the COVID-19 pandemic in Paris, France: a population-based, observational study [published online ahead of print, 2020 May 27]. Lancet Public Health. 2020;S2468-2667(20)30117-1.doi:10.1016/S2468-2667(20)30117-1
  5. Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and Mortality among Black Patients and White Patients with Covid-19 [published online ahead of print, 2020 May 27]. N Engl J Med. 2020;10.1056/NEJMsa2011686. doi:10.1056/NEJMsa2011686
  6. James Watson on the behalf of 146 signatories. (2020, May 28). An open letter to Mehra et al and The Lancet (Version 2). Zenodo. http://doi.org/10.5281/zenodo.3864691
  7. Mehra MR, Desai SS, Ruschitzka F, et al. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID 19: a multinational registry analysis [published online ahead of print, 2020 May 22]. Lancet. 2020;S0140-6736(20)31180-6. doi:10.1016/S0140-6736(20)31180-6

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