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Vincent Rajkumar Profile picture
@VincentRK
Sep 9, 2020 • 6 tweets • 4 min read • Read on X
The mask analogy to a vaccine. My thoughts from April.
@jeremyphoward @Rfonsi1 @zeynep @erikbryn #Masks4All

1/
The common refrain from experts early on was that masks were not needed unless you are sick. I believed this till Mar 29. Then the evidence became too strong that masks were needed for everyone. But the message was that it was only to protect others from you (source control).
2/
But the high rate of serious illness in healthcare workers, the lower mortality in mask wearing countries and COMMON SENSE meant masks must protect the wearer also (work as PPE). People are also more likely to wear a mask of it helps themselves not just others.
3/
The other important message was that while completely preventing infection is hard, masks may preventing serious infection by reducing viral dose. And the whole concept of viral dose and severity that @DrSidMukherjee wrote about in mid March in @NewYorker. Even cloth masks help.
It takes much longer for private citizens (who have a day job) to analyze data & events & come to a conclusion. By late March, many of us were literally screaming for masks ahead of CDC & WHO. The wobbling made the public doubt the unequivocal importance of masks. @jeremyphoward
Any now the messaging should be clear and unequivocal. -Masks protect others from you (source control).
-Masks protect you from others (PPE)
-Masks reduce viral dose and may make the disease milder, & function analogous to a vaccine
-Any mask is OK, except ones with valves

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More from @VincentRK

Vincent Rajkumar Profile picture
May 24
The remarkable story of Velcade.

In the year 2000, a few of us attended an angiogenesis meeting in Boston. We were there to discuss thalidomide

But a side meeting that evening led to trial that went on to get Velcade FDA approved for myeloma. @NEJM

Story in thread. Image
Velcade (bortezomib) was first introduced to cancer research by the name PS-341.

It was a novel proteasome inhibitor developed by Julian Adams and colleagues a a potential anti cancer agent. @CR_AACR @AACR aacrjournals.org/cancerres/arti…Image
The ubiquitin-proteasome garbage disposal pathway in cells is a Nobel prize winning discovery.

Proteins that need to be degraded are tagged with ubiquitin tails. Tagged proteins are degraded by the proteasome complex. (This review has details )

PS-341 was a proteasome inhibitorascopubs.org/doi/10.1200/JC…Image
Read 13 tweets
Vincent Rajkumar Profile picture
May 18
The fascinating story of Thalidomide: how this most notorious drug on the planet, banned in the 1960s, made an incredible comeback and revolutionized the treatment of myeloma.

I will also highlight one person whose role is not recognized: Without Dr. Leif Bergsagel there will be no thalidomide for myeloma.

Read on #MedTwitter
The thalidomide story has many takeaways and lessons.

It shows drug development from bedside to bench and back to bedside.

It shows the power and impact of astute clinicians

It shows the power of investigator courage

The role of serendipityImage
But let’s start at the very beginning.

Thalidomide was synthesized in 1954, and then developed as a sleeping pill by the German company Chemie Grünenthal in the 1950s.

At the time the only sedatives available were barbiturates which had risks of intentional or accidental overdose.Image
Because thalidomide was felt to be a drug that cannot cause death due to overdose it was marketed as one of the safest sedatives.

By 1961, it was sold in over 40 countries as a sleeping. It was also tragically used to control morning sickness of early pregnancy. Image
Read 20 tweets
Vincent Rajkumar Profile picture
Dec 9, 2024
AQUILA trial for high risk smoldering myeloma published in @NEJM today.
@thanosdimop

Personally for me, it is a huge milestone along 25 years of work that started in 1998. #ASH24 #ASH24VR

This story below may help those interested in a clinical trialist career.
1/ Image
In 1998, as a fellow @MayoClinic I was keen to determine if early intervention delayed progression and improved survival in SMM. #ASH24

In 1999, with the help of Tom Witzig, I led a small phase II trial of thalidomide for SMM. @LeukemiaJnl
2/ Image
I was then so fortunate to examine the natural history of SMM, with the legendary Bob Kyle. Honored to be last author on @NEJM paper that also provided data that most progressions occur in the first 5 years of diagnosis.

The start of the concept of high risk vs low risk SMM.
3/ Image
Read 12 tweets
Vincent Rajkumar Profile picture
Aug 24, 2024
Why are prescription drug prices are far higher in the US that other developed countries.

I’ll break it down. A full 360.

1/ We don’t negotiate prices at launch of a new drug. Others do. Image
As a result, we spend billions on common drugs that other countries spend a fraction of the price on.

Some drugs we pay 10 or 100 times more!! Image
2) Generic and biosimilar entry, adoption, and utilization is slower in the US, and there are many barriers.

Timely and adequate free market competition is critically important for lowering price. Image
Read 21 tweets
Vincent Rajkumar Profile picture
Jul 8, 2024
FDA approval doesn’t necessarily mean standard of care.

Thread.
1/
For example FDA approved Dara VMP for frontline therapy in myeloma in 2018.

Literally no one used the regimen in the US.

Literally no one felt the regimen was standard of care in the US.

Before or after approval!
Why?
FDA adjudicates a sponsors submission on whether a given drug/regimen has met the burden of proving safety and efficacy.

Standard of care in clinical practice is a different standard: judgment of risk/benefit of available alternatives, and assessment of trial design/end points.
Read 13 tweets
Vincent Rajkumar Profile picture
Jun 25, 2024
Cure is a simple word. But there is confusion when it comes to cancer. What cure is in cancer, and what we should aspire for?

When can we say that a given type of cancer is curable?
Thread
1/
There is a difference between when we can say a particular cancer is a curable type versus whether individual patients with a given cancer can be considered potentially cured.

They are not the same.
2/
To call a cancer curable we must be able to treat the cancer for a finite duration, stop all therapy, and know that a certain % of patients will never relapse

Early stage solid tumors, Hodgkin lymphoma, DLBCL, ALL, AML are curable. Real cure. The definition of curable cancer
3/
Read 13 tweets

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