It's established that COVID can persist in tissue/blood - particularly in immunocompromised patients - and is associated with long COVID [1]. This abstract only reports a cut-off of >60 days from COVID infection, so it's hard to know how many of these deceased patients are truly outside the acute infection phase.
Although this research area is the most promising avenue for long COVID -- wrt biologic rationale -- the major anti-viral trials for long COVID were negative.
STOP-PASC trial [2] and PAXLC [3] were both 15-day courses of Paxlovid and showed no benefit across patient reported outcomes.
The real question however, is whether anti-virals have benefit in patients with active viral replication. Like only cases of long COVID can be implicated to viral persistence.
STOP-PASC did collect stool PCR at baseline, but every tested sample was negative. PAX LC later reported a exploratory biomarker analysis of 82 PAX LC participants did measure circulating SARS-CoV-2 S1 and full-length Spike, and wasn't powered to find a difference. Notably, spike presence doesn't necessarily mean active viral replication [4].
As an aside, mchusma's post is probably right. Viral disease is not being associated with more and more long term diseases. EBV is being linked to MS, cervical cancer to HPV, and so on.
Your take on Evidence Based Medicine (EBM) is wrong.
At the top of the evidence hierarchy is N-of-1 trials (and below that are high quality meta-analyses of trials). Nothing is more informative about treatment response in a person than testing it in that person. This is the heart of personalized medicine, and exactly for the reason you stated: Different interventions work differently for different people.
And any practitioner worth their salt is unsurprised by this headline. A great example is that illness and inflammation increase insulin resistance via counter-regulatory hormones.
You got one thing right, intuition often turns out to be wrong. That is why the vast majority experimental therapeutics built on great ideas never get passed initial testing.
Small individual study sample size does not necessarily mean junk. Junk is a product of poor methodology. The main concern with sample sizes may be overestimates of effects if the event is rare, or poor precision (ie large confidence intervals).
However you’re right to presume that small studies are likely to be lower quality, often because they’r observational as opposed to randomized studies.
I think you’re spot on about the clear advantage of your approach relative to the article and blood biopsies: If you’re looking for cancer in the blood, you’re probably too late as this suggests metastatic spread.
You suggest something better: look for tissue level markers.
The immunotherapy revolution (ie CTLA/PD1 molecules), you’ll recognize that leveraging the immune system is brilliantly effective.
Presumably stealth genes do not evolve first, but rather proliferative genes. And this is why any chronic damage triggers cancer because renewal is a replicative process, and replications begets copy errors. wanderers and passersby will have to recognize I’m simplifying.
I have a great lateral. Not sure if you have the funds to try two things, but TCR characterization is a wonderful idea. At least thats the best way to do it, as I see it. has many application beyond cancer
The main concern here (and most observational studies) is confounding by indication. Specifically, the same reason some people got hydroxychloroquine as opposed methotrexate is the same reason you see differences in the outcome. In this case there’s plausible confounding that needs to be addressed before any conclusion like the title could be drawn.
Generally hydroxychloroquine is used in mild rheumatoid, whereas methotrexate is used in moderate-severe disease.
Inflammation in rheumatoid (and other inflammatory diseases) contribute to atherosclerosis and plaque buildup. Rheumatoid increases the risk of coronary disease by 1.5-2x.
That difference alone could account for the difference in dementia, particularly vascular dementia.
I'm intrigued about your research and would love to hear more. I'm a physician interested the effect of for-profit care on health care and outcomes.
As an example, we showed that for-profit dialysis facilities in the US have about a 7% higher mortality rate. We did a meta-analysis and every study barring one found higher mortality in for-profit dialysis facilities. Other studies suggest one reason is lower referral rates for kidney transplantation. Higher mortality has also been shown in for profit hospitals.
Yes cholesterol is a vital building block. However the medical literature consistently shows a strong relationship between LDL and non-HDL cholesterol levels and heart attack and stroke.
Various cholesterol lowering drugs, statins being the most widely prescribed but certainly not the only class, show consistent relationship with cholesterol lowering and reduced risk of MACE (MI, stroke).
Plaque is made of foam cells that consume cholesterol. They grow and obstruct arteries, and eventually rupture causing critical flow obstructing events.
That’s a great thought, however, when you look at tissue under a microscope you should see evidence that the immune system was at play. This means the presence of complement activation (an ancient arm of the immune system), antibodies, white blood cells, nuclear debris, and so on. Presumably when they saw no evidence of immune mediated rejection, they saw none of this.
The GLP1s have proven to have excellent efficacy for weight loss (and cardiovascular mortality in diabetics). Their numbers approach bariatric surgery (>10% body weight in the obese).
This piece entirely misses the point of the recommendation.
The new recommendation is that aspirin should not be used to prevent heart attack in those without a history of heart disease (ie avoid routine aspirin for "primary prevention"). Aspirin for primary prevention has always been a grey area. The reversal came after a large trial in the New England Journal of Medicine looking at this. The trial showed the decrease in cardiovascular events was balanced by a similar increase of bleeds. So it's still grey because some people would prefer to bleed because blood is easily replaceable, your heart is not.
What remains clear is that people who have had heart attacks, strokes, or peripheral arterial disease should in most cases continue their anti-platelet agent.
My meaning was that there is no other therapeutic agent available for prevention of post-ERCP pancreatitis. But you're quite right, there must be another reason.
If I had to hazard a guess, it may be the market isn't attractive enough for competitors to establish a national supply chain. Or there's some sort of collusion at play.
To me this represents further evidence why public goods should be left out of the hands of private for profit organizations for whom disease is simply an externality to capitalize on.
Here's the tale: If you have obstruction of your bile ducts below the liver or gallbladder, usually gallstones or sometimes neoplasm, you need an endoscopic retrograde cholangiopancreatography (ERCP) for extraction or sampling.
ERCP is sticking a tube down the throat, stomach, small intestines into a tiny opening at the ampulla of Vater to access the bile ducts. Sometimes this process causes inflammation of the ampulla and associated ducts leading to blockage, and can lead to pancreatitis due to back flow and pressure, because the pancreas also excretes its digestive enzymes via the ampulla).
A few trials circa 2015 showed rectal indomethacin reduced the risk of post-ERCP pancreatitis, and eventually it made its way into the guidelines. It is the only proven preventative treatment, so they have a natural monopoly.
I did not bother to read this thread in its entirety though I typically enjoy HN discussion.
Undoubtedly, masks of any quality work. Airborne viruses still exist in secretions (likely, in much higher concentrations). Secretions sometimes even carry living cells, would you imagine (in fact the #1 cause of sputum sample contamination for C&S; the bane of internists everywhere). High velocity events certainly increase the environment-load of secretion and thereby virus.
You don't need evidence in all cases. Im sorry to say, to the otherwise curious-minded, this is one of those cases.
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