Discover and read the best of Twitter Threads about #howireadthispaper

Most recents (18)

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…
3/
Returning to COMET-ICE: what was studied?

Patients were randomized (double-blind) to receive a one-time IV infusion of SOT or placebo.

The primary outcome was the relative reduction in patients hospitalized for >24h or who died from any cause through day 29.
Read 18 tweets
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.
3/
What was studied?

Patients were randomized (double-blind) to receive IV RDV or placebo x 3 days

The primary outcome was the composite of COVID-related hospitalization or death from any cause by day 28.
Read 15 tweets
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…
3/
In which patients was this drug studied?

1,433 unvaccinated outpatients

>18 years old

with symptomatic #COVID19

for <5 days

and at least one risk factor for severe disease:
Read 18 tweets
Here is a short #Tweetorial on #HowIReadThisPaper which aims to address whether combinatorial treatment with temozolamide and riluzole is effective against glioblastoma

doi.org/10.3171/2019.1…

@MedicsAcademy
#NeuroOncology
MGMT might make you think of millennial electropop, but read on to find out what else it should make the keen #NeuroOncologist think of.

open.spotify.com/track/1jJci4qx…
1/
Glutamatergic signalling promotes growth in glioblastomas. Riluzole is a glutamate receptor 1 inhibitor shown to suppress GBM growth. Temozolamide is an established chemotherapeutic agent for the treatment GBM. However, the combined effects of these drugs are unknown.
Read 11 tweets
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.
3/
First, let’s agree on what was tested:

The hypothesis was that the recommendation to wear masks (added to other public health measures) would reduce the incidence of COVID19 among wearers from 2% to 1% over 1 month, in a setting where mask use was uncommon (Denmark).
Read 24 tweets
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:

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:
3/
Background: COVID19 can induce a deadly hyper-inflammatory host response.

Prior observational data (↓quality, ↑risk of confounding by indication) suggested ↑mortality from steroids in influenza: pubmed.ncbi.nlm.nih.gov/30798570/

The role of steroids in treating COVID19 is unknown.
Read 17 tweets
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”)
3/
Amazingly, ~15% of all patients hospitalized for COVID19 in the UK during the study period were included in this trial.

No other Tx trial for COVID19 even comes close to that level of representation.

→These results should generalize broadly to hospitalized patients.
Read 15 tweets
1/ A #MedTweetorial on #HowIReadThisPaper for #DISCOVERYtrial - dex edition on @medrxivpreprint. We’ll be exploring the pre-print, supplement, and trial document. Would love for feedback, thoughts, & comments!

Currently, what is your opinion on using dexamethasone?
2/ Trial info:

▶️RCT, open-label, adaptive
▶️6,425 pts enrolled
▶️Dex 6mg daily for 10d (PO or IV) v usual care (1:2 ratio, respectively)
▶️176 🏥in UK
▶️Prim Outcome: OS

🔑Intention-to-treat
🔑Pre-specified stats plan
🔑Not randomized by O2 status
3/ Results - Table 1
✅Well-balanced between dex & usual care
▶️Younger, less-comorbid cohort on vent
▶️Days of illness ⬆️w/ ⬆️O2

Imbalances in O2/vent cohort raises ❓s
1️⃣How to account for O2 & vent?
2️⃣Can we adjust & trust result?
Read 14 tweets
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?
3/
Chua et al annemergmed.com/article/S0196-…

Question: What are the test characteristics of acute olfactory loss (hyposmia or anosmia for <14d) for Dx of COVID19, using oropharyngeal PCR as the gold standard?

Design: single-center cross-sectional study via chart review (retrospective)
Read 17 tweets
How COVID-19 spread like wildfire 🔥 via a series of well-attended indoor church events in a town in rural Arkansas.

A #MedTwitter summary of this paper in 7 tweets:

James A, Eagle L, Phillips C, et al. in @CDCMMWR
DOI: dx.doi.org/10.15585/mmwr.…

🧵(thread) Image
1/
2 persons attended church events while symptomatic on March 6-8 and later tested (+) for COVID-19 (primary cases).

The church pastor and his wife also attended these events and became ill ~4 days later (Mar 10-11) (index cases).
2/
The church was closed on Mar 12, but prior to that 92 people had attended church events from Mar 6-11.

Of those 92 people, 35* (38%) tested (+) for COVID-19.

Notably, this was 35 of the 45 people tested, representing a 77.7% positive test rate (!!)
Read 9 tweets
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:
3/
Background: A 2003 case series suggested ↓mortality (vs historical controls) in SARS patients treated with LPV/r + RBV :

ncbi.nlm.nih.gov/pmc/articles/P…

In 2015, LPV/r and IFN led to ↓viral load and improved clinical outcomes in animal models of MERS:

pubmed.ncbi.nlm.nih.gov/26198719/
Read 30 tweets
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:
3/
Background: There are currently no effective antivirals for patients with severe COVID19.

RDV, a nucleotide analogue, has broad antiviral activity against many coronaviruses in vitro.

This is the first published clinical trial of RDV for #COVID19 in humans.
Read 30 tweets
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.
3/
Question: What is the cumulative incidence of venous and arterial thrombosis among critically ill patients with #COVID19?

Date published: 10 April 2020

Funding: None specified
Read 28 tweets
1/
Is my hospital workstation contaminated with SARS-CoV-2?

Here’s: #HowIreadThisPaper from @CDCgov's J of Emerging Inf Diseases on aerosol and surface distribution of the virus that causes COVID-19 in a hospital in Wuhan, China.

wwwnc.cdc.gov/eid/article/26…

#Tweetorial 🧵 Image
2/
Study goal: systematically assess contamination of hospital environment w/ SARS-CoV-2. Areas studied were a COVID+ ICU and an isolation general ward (“GW”). Authors stated the ICU had 15 pts w/ “severe” dz, and GW had 24 pts w/ “milder” dz. No mention of mechanical ventilation
3/
SETTING

🔦HIGHLIGHT #1: the layout of their COVID+ care units is pictured here. Does this look like your hospital’s COVID+ units?
I suspect the answer is a strong no. Take a look. This will be important in applying any of their results to your own hospital. Image
Read 26 tweets
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.
3/
Question: What were the outcomes among patients hospitalized with #COVID19 who received RDV on a compassionate use basis?

Date Published: 10 April 2020

Funding: Gilead Sciences
Read 27 tweets
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.
3/
Question: Is LPV/r safe and efficacious for shortening time to clinical improvement in patients hospitalized with #COVID19?

Date Published: 18 March 2020

Funding: Major Projects of National Science and Technology on New Drug Creation and Development
Read 29 tweets
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.
3/
Question: Does HCQ shorten the duration of viral shedding in patients with #COVID19?

Date Published: 17 March 2020 (In Press)

Funding: Agence Nationale de la Recherche (Government of France)
Read 22 tweets
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
3/
Study Design: Case series

Population: 1,099 patients hospitalized in China with RT-PCR confirmed #SARSCoV2 (nasal or pharyngeal swab)

Study Period: 12/11/2019 - 1/29/2020
Read 14 tweets

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