1/
A patient receiving his first-ever dose of IV Iron (ferumoxytol) suddenly develops diffuse face & trunk flushing, chest pain, myalgias, and anxiety.

Blood pressure is normal and lungs are clear.

You are called to the bedside to assess.

How likely is anaphylaxis? 2/
To decide on the answer, let’s review the diagnostic criteria for anaphylaxis.

The 2006 NIAID/FAAN guidelines say anaphylaxis is likely if one of the three criteria below are fulfilled:

A key feature is rapid onset (within minutes to hours).

sciencedirect.com/science/articl…

1/
You suspect pneumonia, but the CXR shows no opacities.

Q: When should you obtain a chest CT?

Pick your answer, then read on for a short explanation

(PTP = pretest probability) 2/
Imagine two patients with cough whom you are working up for PNA:

Patient A: also has sudden-onset pleuritic chest pain, WBC 10, T=98.3

Patient B: also had malaise and fatigue for 2-3 days, WBC 15, T=100.7.

Before imaging, who sounds more like they have PNA?

1/
Should you use Sotrovimab (SOT) to treat high-risk outpatients with #COVID19?

Spoiler alert: Yes, if you can find it.

Here's #HowIReadThisPaper on the COMET-ICE trial by Gupta et al in @NEJM

nejm.org/doi/full/10.10…

(Thread) 2/
The origin story of SOT is amazing:

It was developed from an antibody in a frozen blood sample from a patient who survived the SARS epidemic of 2003.

It binds to a highly conserved part of the coronavirus spike protein and blocks cell entry.

nature.com/articles/d4158…

1/
Should we use #remdesivir (RDV) to treat high-risk outpatients with #SARSCoV2 #COVID19?

Here's #HowIReadThisPaper on the PINETREE trial by Gottleib et al in @NEJM

(Thread)

nejm.org/doi/full/10.10… 2/
High-quality evidence suggests RDV shortens time to clinical improvement in hospitalized patients with #COVID19 and hypoxemia (ACTT-1).

Based on this, @NIH recommends RDV in hypoxemic inpatients:

covid19treatmentguidelines.nih.gov/management/cli…

However, its role in treating outpatients is unknown.

1/
Should we use #molnupiravir (MOV) to treat #SARSCoV2 #COVID19?

With new @NIH treatment guidelines out, it's time to review the evidence behind them.

Here's #HowIReadThisPaper on the MOVe-OUT trial by Bernal et al in @NEJM

(Thread)

nejm.org/doi/full/10.10… 2/
How does this drug work?

MOV is a RNA nucleotide prodrug of n-hydroxycytidine, a cytidine analogue that is a potent mutagen for viruses.

It works by tricking viral RNA polymerase into making errors during replication.

nature.com/articles/s4159…

1/
My appraisal of the Danish mask study (DANMASK-19): This was a negative trial - masks were not shown to prevent #COVID19.

Could chance or bias make this outcome more likely?
Does this mean we don’t need to wear masks?

Let’s take a deeper look.

#HowIReadThisPaper

(Thread) 2/
Before beginning, if you have not already done so, I implore you - read the paper!

acpjournals.org/doi/10.7326/M2…

Then, come back, and please comment, add what I have missed, and correct me where I am wrong.

Critical appraisal is a group effort.

1/
#SARSCoV2 #COVID19 got you down? Me too.

Ready for some good news? Here it is: #Dexamethasone (dex) works.

But when, how much, and for which patients?

Here’s #HowIReadThisPaper on Horby et al: the RECOVERY trial prelim report: nejm.org/doi/full/10.10…

(Thread) 2/
Already read the paper, just want the appraisal? Go here:

https://twitter.com/rbganatra/status/1287029901204357121?s=20

Haven’t read it yet? Here are the highlights.

Based on my very informal poll, here’s how twitter respondents indicated they are using dex in COVID19 patients as of mid-July 2020:

1/
My appraisal of the RECOVERY trial: This was a (very) positive study.

How could chance or bias affect the validity of these results?
What was missing?
How should we apply these results?

Let’s take a deeper look.

#HowIReadThisPaper 2/
Regarding bias: Strict inclusion/exclusion criteria can introduce selection bias by creating a highly selected study population.

This was NOT so in RECOVERY.

In figure 1, we see that 83% of recruited* patients were ultimately included.

(*assuming “recruited” = “screened”)

1/
How common is loss of smell (anosmia) in #SARSCoV2 #COVID19, and how useful is it for ruling the diagnosis in or out? Let’s take a look at the data.

Here’s a quick #HowIReadThisPaper on two @AnnalsofEM papers addressing this question:

Chua et al

&

Peyroney et al

(Thread) 2/
First, a question:

Let’s assume you have a limited supply of swabs and need to prioritize which patients to test for COVID19.

In which skilled nursing facility (SNF) setting would you expect anosmia to be more useful in identifying patients who will test positive?

1/
Should we use #Lopinavir-ritonavir (LPV/r) + #Ribavirin (RBV) +/- #Interferon beta-1b (IFN) to treat #SARSCoV2 #COVID19? Let’s take a look at the data.

Here’s: #HowIReadThisPaper on @TheLancet trial of triple therapy for COVID19

Hung et al: thelancet.com/journals/lance… 2/
First, let’s assess our baseline beliefs about triple therapy:

Before reading this study, when considering triple therapy as a treatment for patients with COVID19, I think the most important component is likely to be:

1/
Should we use #Remdesivir (RDV) to treat #SARSCoV2? #COVID19 Let’s take a look at the data.

Here’s: #HowIReadThisPaper on the @Lancet trial of RDV for COVID19 in humans

Wang et al: thelancet.com/journals/lance…

(Thread) 2/
First, let’s assess our baseline beliefs about RDV.

Before reading this study, when considering remdesivir as a treatment for patients with severe #COVID19, I think the:

1/
What is the risk of macrovascular thrombosis among critically ill patients with #SARSCoV2 #COVID19? Let’s take a look at the data.

Here’s #HowIReadThisPaper on a @ThromboisRese1 case series examining this question:

Klok et al: thrombosisresearch.com/article/S0049-…

(Thread) 2/
Background: #COVID19 can cause inflammation, hypoxemia, and disseminated intravascular coagulation (DIC), which all increase risk for venous (DVT, PE) and arterial (CVA, MI) thrombosis.

Currently, the risk of thrombosis in patients critically ill with COVID19 is unknown.

1/
Should we use #remdesivir (RDV) to treat #COVID19 #SARSCoV2? Let’s take a look at the data.

Here’s: #HowIReadThisPaper on the @NEJM case series of remdesivir for COVID19:

Grein et al: nejm.org/doi/full/10.10…

(Thread) 2/
Background: RDV is an ATP analogue that inhibits many viral RNA polymerases in vitro, including MERS-CoV and SARS-CoV1+2. However, in an RCT of 4 drugs for ebola, RDV was ineffective:

nejm.org/doi/full/10.10…

It does not currently have an FDA-approved indication for use.

1/
Should we use #lopinavir-ritonavir (LPV/r) to treat #COVID19 #SARSCoV2? Let’s take a look at the data.

Here’s: #HowIReadThisPaper on the @NEJM trial of LPV/r for COVID19 in humans: LOTUS China

Cao et al: nejm.org/doi/full/10.10…

(Thread) 2/
Background: Lopinavir, an HIV protease inhibitor, is active in vitro against SARS-CoV and in animal models of MERS-CoV. Ritonavir inhibits CYP3A and increases serum half-life of lopinavir. A 2004 uncontrolled study of LPV/r + ribavirin suggested a benefit in SARS in humans.

1/
Should we use #hydroxychloroquine (HCQ) +/- azithromycin to treat #COVID19 #SARSCoV2? Let’s take a look at the data.

Here’s: #HowIReadThisPaper on the only trial published to date on HCQ for COVID19 in humans:

Gautret et al: mediterranee-infection.com/wp-content/upl…

(Thread) 2/
Background: HCQ has antiviral activity against SARS-CoV-1 in vitro, is already available in much of the world, and has a known side-effect profile. It was used for #COVID19 in China, but data on clinical outcomes are not yet available.

1/
Feeling overwhelmed by the #COVID19 #SARSCoV2 literature? Me too.

We’re in this together. I’ll show you #HowIReadThisPaper and my appraisal. Add, comment, and correct me where I am wrong.

First up: nejm.org/doi/full/10.10…

(Thread) @BostonChiefs @Curbsiders 2/
Question: What were the clinical features of #COVID19 among patients hospitalized in China in the first 2 months of the outbreak?

Date published: 2/28/2020

Funding: National Health Commission of China