This week’s top 5 flash update has been taken over by the Centre for Urgent and Emergency Care Research (CURE) team at the University of Sheffield.

CURE boasts a diverse portfolio of research spanning across the whole urgent and emergency care system including ambulance services, GPs, and emergency departments. They have expertise in data linkage, complex modelling, clinical trials and qualitative research. Current projects include the CUREd dataset, a complete 5-year linked dataset of ambulance service, ED and inpatient data for analysis. They also have active studies in prognosis and risk prediction including MATTS, PHEWS, PAINTED (PRIEST) and SINEPOST. Their qualitative research has been focused around the whole system. For more information about CURE, see here.

If you would like to join this exciting team, there is currently a PhD opportunity, for more information click here.

There were 882 papers this week, and the CURE team have gone through them all to find the best ones for you to read! These are the quick and dirty summaries, but all of the material and links are online, so please do check these articles out in full if you are interested!

As in previous weeks, these papers have been split into 3 categories that will allow you to focus on the papers 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

RCEM COVID-19 CPD Journal club CURE TakeoverWeekly top 5 papers

Jamie Miles, Dr. Susan Croft, Colin O’Keeffe, Jo Coster, Maxine Kucsawski, Dr Carl Marincowitz,Dr. Mike Tonkins, Professor Simon Carley, Professor Suzanne Mason, and the RCEM COVID-19 CPD team

Join the team on Twitter

@CURE_ScHARR @999EMJamie @DrSusieC @ColOKeeffe@joannecoster @kuczawski1010 @CarlMarincowitz @MikeTonkins@EMManchester @ProfSueMason

The RECOVERY trial is an individually randomized, controlled, open-label, adaptive platform evaluating the effects of potential treatments in patients hospitalized with COVID-19. The trial was conducted at 176 National Health Service (NHS) hospital organizations in the UK. The study is examining multiple treatments including low-dose dexamethasone, lopinavir-ritonavir, azithromycin, tocilizumab, and convalescent plasma. To find out more about the whole trial, see here. This flash summary is a pre-print of the effects of dexamethasone.

There was a total of 6425 patients enrolled on a 2:1 ratio of usual care, or usual care + dexamethasone 6 mg once daily (oral or IV) for up to 10 days (or until discharge if sooner). Their primary outcome was 28-day all-cause mortality. The key result is that for mechanically ventilated patients with COVID-19, the use of dexamethasone reduced their mortality by a third (rate ratio 0.65 [95% CI 0.51 to 0.82]). It also reduced 28-day mortality by a fifth in those receiving oxygen without invasive ventilation (rate ratio 0.80 [95% CI 0.70 – 0.92]). However, there was no evidence to support the benefit of dexamethasone for those who are not receiving any respiratory support (rate ratio 1.22 [95% CI 0.93-1.61]).

It is crucial if you are to read the pre-print, also examine the supplementary material found here.

Whilst the study results appear significant, it is important to remember this is a non-peer reviewed pre-print. The participants in the control and intervention arm are similar, however

there were characteristic imbalances between the level of respiratory support required such as gender and time since onset at randomisation. Therefore, this

intervention might not be as effective in older patients (over 70 years), women, or those with onset of symptoms < 7 days (all statistically insignificant on sub-group analysis).

Effect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report by the RECOVERY Collaborative GroupTopic: TreatmentRating: Game changerScout: Jamie Miles

Elevated D-dimer levels have been recognised as prognostic factors for more severe cases of COVID-19. This observational study undertaken at a University Hospital in Wuhan in early 2020 assesses the accuracy of normal versus elevated D-dimer levels for predicting survival at 28 days.

749 out of 761 consecutive patients had presenting D-dimer information at day 1 and were included in the analysis. Normal D-dimer levels predicted 28 day survival with high precision at both day 1 and day 3. D-dimer levels on day 1 were normal in 87% of survivors but elevated in 46% non-survivors (survival sensitivity of 87% (95% CI = 86% to 89%), positive predictive value of 93% (95% CI = 92% to 95%), specificity of 46% (95% CI = 36% to 57%), and negative predictive value of 30% (95% CI = 23 to 36%)).

This has implications for patient triage and hospital admission decisions, with the authors asserting that patients with elevated D-dimer levels awaiting COVID swab test results could be assumed to be COVID positive and triaged as higher risk, whereas patients with normal D-dimer

levels and no other hospitalisation factors could be managed as outpatients.

Furthermore, D-dimer testing in prehospital settings (e.g. using rapid point of care D-dimer blood tests) could aid ED conveyance decisions for patients with suspected COVID-19.

D-dimer triage for COVID-19 by Li et alTopic: PrognosisImpact rating: Head Turner Scout: Jo Coster

Covid-19 is affecting all hospitals in the UK but are they all performing as well in treating the patients? This observational study tracks mortality data across UK intensive care units and shows a wide variation in patient prognosis. The Hazard ratios of ICU location are equivalent in magnitude to the strongest prognostic predictor we know to date (age), ranging from 0 to +4. There appears to be a trend for units

with larger numbers of patients to have lower mortalities on my interpretation of the data (more narrow confidence intervals). Of course, this observational type

of study is prone to a great deal of bias and we know little about the patient characteristics, but that said, the wide variation in mortality asks questions about the calibration of care for our sickest COVID-19 patients.

Between-centre differences for COVID-19 ICU mortality from early data in England by Qian et alTopic: Observational Impact rating: Worth a peekScout: Professor Simon Carley

Antibody testing for SARS-CoV-2 infection has been made available to high risk health care workers, including those working in Emergency Departments, by many NHS trusts. A positive test is commonly interpreted by those undergoing testing to mean that they have had COVID-19 infection, mounted a successful immune response and are no longer susceptible. A negative test is thought to imply the opposite. This Cochrane review highlights the known limitations of current antibody testing and weaknesses in the available evidence.

The review included 54 studies and 15,976 samples. The sensitivity of antibody testing was highly dependent on when the test was taken in relation to the onset of symptoms, with a pooled sensitivity of 24.5% (9.5 to 50.0) if taken within a week of onset compared to 98.1% (90.1 to 99.6) if taken at 3 weeks. The review highlighted that no data were available on testing after 5 weeks of symptom onset and that IgM based tests are likely to be less accurate as time from symptom onset increases. Almost all studies were conducted on patients who had been hospitalised and therefore the accuracy of antibody tests in identifying healthcare workers who have had mild or asymptomatic infection is not known. There is no available evidence to indicate whether a positive antibody test is associated with a lower risk of developing subsequent COVID-19 infection.

Therefore, health care workers need to interpret the results of any antibody testing with caution. The accuracy of the results is highly dependent on when, and potentially how severely, the infection occurred and may not be associated with a reduced susceptibility to further infection.

Antibody tests for identification of current and past infection with SARS-CoV-2 by Deeks et alTopic: DiagnosticsImpact rating: Head Turner Scout: Carl Marincowitz

The RECOVERY Collaborative Group concluded that low-dose dexamethasone in COVID patients who need respiratory support is beneficial 1

Game changer summary

In summary

Qian et al showed there was a difference in mortality between ICUs in England 2

Li et al found that a normal D-Dimer on day 1 was associated with 28-day survival 3

Deeks et al present a robust argument against drawing strong conclusions from an antibody test result 4

Liu et al found younger people are suffering with increased mental health morbidity as a result of the pandemic 5

There is potential for the public health response to the pandemic to cause an upsurge in mental health morbidity in younger people and is therefore important to assess. As part of a larger longitudinal study, an online cross-sectional survey was undertaken of young adults across the United States between 18 and 30, to measure depression, anxiety and

PTSD, along with psychological experiences such as loneliness and support. A third of the sample reported elevated clinical levels of depression, anxiety and PTSD on

validated scales, considerably higher than previous studies of similar populations using the same measures. Factors influencing these outcomes included loneliness, levels of family support and resilience levels. Interventions for younger people targeting these constructs are important.

Factors associated with depression, anxiety, and PTSD symptomatology during the COVID-19 pandemic: Clinical implications for U.S. young adult mental health by Liu et al Topic: Psychological effectsRating: Worth a peek Scout: Colin O’Keeffe

References

1) RECOVERY Collaborative Group. (2020). Effect of Dexamethasone inHospitalized Patients with COVID-19 - Preliminary Report. MedRxiv Preprint.doi.org/10.1101/2020.06.22.20137273

2) Qian, Z., Alaa, A. M., Van Der Schaar, M., & Ercole, A. (n.d.).Between-centre differences for COVID-19 ICU mortality from early data inEngland. doi.org/10.1101/2020.04.19.20070722

3) Li, C., Hu, B., Zhang, Z., Qin, W., Zhu, Z., Zhai, Z., … Wang, C. (2020). D-dimer Triage forCOVID-19. Academic Emergency Medicine, acem.14037. doi.org/10.1111/acem.14037Liu, C. H., Zhang, E., Wong, G. T. F., Hyun, S., & Hahm, H. “Chris.” (2020)

4) Deeks, J. J., Dinnes, J., Takwoingi, Y., Davenport, C., Spijker, R., Taylor-Phillips, S.,… Cochrane COVID-19 Diagnostic Test Accuracy Group. (2020). Antibody tests foridentification of current and past infection with SARS-CoV-2. The Cochrane Database ofSystematic Reviews, 6, CD013652. doi.org/10.1002/14651858.CD013652

5) Factors associated with depression, anxiety, and PTSD symptomatology during theCOVID-19 pandemic: Clinical implications for U.S. young adult mental health. PsychiatryResearch, 290, 113172. doi.org/10.1016/j.psychres.2020.113172