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.
That's not accurate at all. A lot of tumors cannot be safely cut out or else they'd just cut out all tumors. Many climb around arteries and other critical areas.
Debulking most of the time isn't an option so if you can use this sound wave thing then that would be a game changer.
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
> If you’re looking for cancer in the blood, you’re probably too late as this suggests metastatic spread.
Isn’t the point of cfDNA that you can pick up “dead” DNA fragments floating around long before you have viable cancer cells drifting through the bloodstream and lymphatic system?
Yes. Normal cells break apart all the time. If you measure total cfDNA amount in a blood sample, you'll find significantly a higher cfDNA concentration after you exercise. It's a normal part of the wear and tear of cells.
So, if you find cfDNA from a tumor, it's not necessarily indicative of metastatic spread... just that the tumor cells have been broken up. It could be from too much growth, or immune attack, or metastasis, or... etc.
cfDNA is great in that you can run a single assay to cover the entire body. cfDNA is difficult because your single assay covers the entire body. You can't localize the source of cfDNA.
> personal history of sudden cardiac death with a persistent risk factor
Personal history, or family history? Maybe this is a technical term? As a non-medic I can’t imagine there are many people who have a history of sudden death AND a persistent risk of it happening again.
"Many" is relative. We are talking about a fraction of a percent of the general population, but if you are looking specifically at the population of people who have some form of long standing heart disease, it's not terribly rare. I don't work in cardiology specifically, and even so I encounter one or two patients a year who have had an ICD placed for reason #3.
Persistent risk factors include things like or overgrowth of muscular heart tissue (which has dozens of causes, but the most common is severe, long standing coronary artery disease) or scarring of the heart after a heart attack.
Persistent risk factors are not rare at all. The thing is that most people who fall into bucket 3 also fall into buckets 1 or 2. So in an ideal world they would have already seen a cardiologist and had an ICD placed before they ever had an episode of SCD. And of course many of those who do have SCD don't survive long enough to have an ICD placed.
If you are interested in reading more, you can search for "secondary prevention of sudden cardiac death" or "secondary prophylaxis of sudden cardisc death." There are some good review articles available online.
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.
It was a long time ago, so I'm operating off questionable memory here, but IIRC the major tell was looking at patient longevity (questionable hospices had longer patient tenure, presumably because of more aggressive recruitment of non-EOL pts) and distribution of inpatient care days (which have the highest reimbursement rate, so questionable hospices tended to max out inpatient days). There was definitely a correlation between size of hospice and those variables, and hospices involved in DOJ/HHS prosecutions were correlated with longer pt tenure and high utilization of inpatient care.
Your work sounds interesting and enlightening -- I'm not familiar with dialysis facilities clinically or from a business PoV, but I'm curious if they suffer from some of the same incentives issues as hospices, given the significant Medicare/Medicaid spend in that area, and the number of ESRD policy carve-outs.
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.
Cholesterol is mostly produced by the liver, fructose consumption plays a significant role in stimulating that process. AIUI dietary cholesterol is mostly a red herring according to current science.
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.
Your point that this is uncharted territory is well-taken, we can't say for sure, but the above poster has it right. I do not know of any circumstance in medicine in which evidence of immune reaction against foreign material would be non-obvious. I'm a pathologist and this is my area of expertise.
We may not know what causes rejection, but are pretty good at seeing the signs of it. Extreme example: if a house collapses, you may not know immediately why it collapsed, but all the debris on the ground is a pretty good sign it's not in one piece anymore.
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.