1) As one of the first people to raise the possibility that not everyone may be susceptible to COVID, and that cross reactive immunity may be protecting some people from severe infection, I agree with those points by @RandPaul
2) I’ve also been on record that seroprevalence underestimates the proportion of people who are immune & that we may be closer to herd immunity in prior hotspots than the 5-10% seroprevalence indicates. But that number (~2 times seroprevalence) is still far short of herd immunity
3) Having said here are 3 comments I disagree with.
-The comparison of NY to Sweden is not correct.
-The statement that flattening the curve does not reduce number of deaths is not correct
-We are doing as well as S. America & so mitigation strategies don’t help is not correct
Sweden as Dr. Fauci pointed out did not do anywhere as well as Denmark, Finland, or Norway—its neighbors. Those are the comparators. Sweden also had warning that NY didn’t have. So we cannot compare. Both Sweden and the US have done equally badly in terms of deaths per million.
Flattening the curve will spread CASES over time and so the area under the curve for cases may be similar whether you flattened or now. But not DEATHS. In fact, the whole idea of flattening the curve is to reduce high number of deaths that occurs when the system is overwhelmed
In fact NY, NJ and the east coast were hit BEFORE the flattening happened. The high death tolls there reflect what happens when the curve is NOT flattened. There is a lag between issuing mitigation orders and flattening to occur. Same thing happened in Lombardy.
We made a lot of mistakes. I have catalogued things we could have done better in hindsight. An earlier recommendation for universal masks would have helped. And a uniform bipartisan recommendation on that. We have fared really badly compared to most developed countries.
The reason why S. Korea, Vietnam, Japan, Taiwan, and China have done so well is far less likely to be related to cross reactive immunity but rather related to strict border control for entry into country, testing, tracing, masks. They followed the science. We didn’t.
I agree that it’s possible that S. America, Africa, India, Pakistan have lower mortality because of cross reactive immunity from prior corona viral infections. But we likely have much less cross immunity. So if we had less social distancing like them, we would have 400,000 deaths
Some links. On susceptibility and cross reactive immunity.
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.
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…
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 )
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 serendipity
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.
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.
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/
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/
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/
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.
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
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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
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