TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.
This week's topics include methotrexate for knee osteoarthritis, impact of new CVD risk calculator, blood tests for Alzheimer's, and evaluating squamous cell cancers.
Program notes:
0:36 Blood tests for Alzheimer's
1:35 Predicting with a blood test accurate 91%
2:35 Less likely than just demographic data
3:30 Squamous cell carcinoma
4:30 Standardize guidelines
5:34 Common cancer excluded from tumor registries
6:15 CVD risk assessment
7:15 Less diabetes secondary to statins
8:15 7.5% risk should be modified?
9:20 Methotrexate for knee osteoarthritis
10:21 Addition did decrease knee pain
11:25 With elevated C-reactive protein
12:28 End
Transcript:
Elizabeth: Does methotrexate help folks with knee osteoarthritis?
Rick: Are blood tests for Alzheimer's disease ready for prime time?
Elizabeth: How should we evaluate squamous cell skin cancers?
Rick: And refining cardiovascular risk assessment.
Elizabeth: That's what we are talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I'm Elizabeth Tracey, a Baltimore-based medical journalist.
Rick: And I'm Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I'm also dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, how about if we turn straight to JAMA? This is some pretty big news relative to, can we detect Alzheimer's disease in blood?
Rick: The title is exactly what the editorialists did. "Are Blood Tests for Alzheimer's Disease Ready for Prime Time?" We now have what's called mass spectroscopy tests and we have very ultrasensitive immunoassays looking at what's called the tau protein, and also looking for different types of amyloid protein in the blood. There were two studies in JAMA that looked at two different issues -- could you use these blood tests to accurately make a diagnosis of Alzheimer's disease?
They took large cohorts of individuals in Sweden -- and these are patients that were being evaluated -- either they had mild dementia, or they had mild cognitive impairment, or they just had subjective cognitive decline. They looked at the accuracy of establishing Alzheimer's diagnosis with their primary care individuals, with a specialist, and then using the blood test.
The accuracy of predicting the presence of Alzheimer's disease pathology, either with PET scan or cerebrospinal fluid, based on the clinical evaluation alone, the primary care doctors were accurate about 61% of the time, the specialty care 73% of the time, but with a blood test about 91% of the time. That was largely driven, by the way, with the tau blood measurement. They were very good for individuals that had cognitive impairment, but they weren't very good in people that have subjective cognitive decline.
Can you use these in the pre-symptomatic phase? That was the second study. They had thousands of individuals -- and they have blood tests over decades -- and they measured amyloid and tau proteins in these individuals. As we age, these markers increase. They increase more in individuals that go on to develop Alzheimer's disease. But their predictive value is actually pretty low. They increased the predictive performance by about 15%. In fact, they were less likely to predict Alzheimer's than using just demographic data.
Elizabeth: This has got a bunch of messages, it sounds like to me. One of them is those who have subjective decline -- and I would include you and me in that group -- where sometimes we walk into the room and say, "Well, why did I come in here?" We shouldn't put our minds at rest that, in fact, gosh, in those folks it didn't predict very well at all, so maybe there really isn't any disease. It's just what happens.
But there is also the idea that maybe we can avoid some of these more invasive tests at some point if we're able to do this with blood tests. Finally, I would say that until we have something that's really effective to offer people with regard to treatment, a lot of this is really only going to be helpful in terms of establishing real numbers about who is impacted.
Rick: You're right. I think, over the next several decades, we are going to be better at both establishing the diagnosis, but also finding additional treatments.
Elizabeth: Turning to JAMA Dermatology. This is a look at squamous cell carcinoma, which really informed me about a bunch of facts that I had no idea about with regards to this type of skin cancer. It turns out that this cutaneous squamous cell carcinoma is the second most common malignant disease in the United States. Most of these squamous cell carcinomas don't result in any mortality. However, some of them do. Because it's of such high incidence, this aggressive subset is estimated to either equal or even surpass melanoma with regard to mortality risk, which -- I had no idea.
They convened an expert panel to determine how to standardize guidelines for looking retrospectively and observationally at cutaneous squamous cell carcinoma. That's really what this is all about. The other part that they note in here is that squamous cell carcinoma is rising in incidence, so this is something that clearly needs to be done. They agreed on high-risk tumor features, local recurrence, parotid metastasis -- so, metastasis into the parotid gland in the cheek -- and then looking at the regional lymph nodes and determining how they are going to impact on the disease progression.
The editorialist notes that this is probably an area that's going to be transformed pretty shortly as we employ AI and the ability of large language models to gather this data and actually look at all these different factors that are related to prognosis, and even incidence of squamous cell carcinoma, and say that it's "painfully evident," I quote, that methods relying on the ICD codes alone are really bad at identifying distinct skin cancers, let alone differentiating the different types of skin cancer one from another. I had no idea that this was such a big problem, and I'm happy that they are trying to create some consensus around it.
Rick: It's surprising. I mean, as common as this cancer is, it has been excluded from national tumor registries. Figure that!
Now what they have to do, besides looking at prospectively -- a lot of institutions have data on thousands and tens of thousands of patients. So we need to look at these large institutional cohorts and all of the systematic reviews, and look at those retrospectively. These definitions that they propose will be incredibly important.
Elizabeth: Just to remind folks that, if they are asked if they can have their data shared for this particular purpose, that it would be really good to do it.
Rick: Yes. Since we are talking about data, let's talk about cardiovascular risk assessment for a minute. This is a study that was published in JAMA.
We know that there are risk factors for developing cardiovascular disease and, obviously, we want to try to prevent those. We use our more aggressive therapies in those individuals that have the highest risk. Again, that's because cardiovascular disease still remains a leading cause of death in the U.S. and globally.
Because there is concern that cardiovascular risk assessment overestimated the risk and therefore we may be treating a lot of people that don't need to be treated, they have developed a new risk assessment. This was data from about 25 different studies that included over 3.2 million individuals to establish what are called the PREVENT equations. Let's compare the new equation and see how it would change care compared to the old equation.
With the new equation, approximately half of all U.S. adults would be classified to a lower-risk category. Okay, so there are a lot fewer people taking medications. What would be the overall outcome? There would be an additional 107,000 MIs [myocardial infarctions] or strokes each year, and about 58,000 less diagnoses of diabetes, which seems to be associated with statin use. I'm going to take a step back and say there is no perfect risk equation, but I think this will help individuals talk to their doctors to decide how aggressively would they want to be treated.
Elizabeth: Will you please step back and explain this assertion that you made, this relationship between statin use and diagnosis of diabetes?
Rick: Right. It's a very small association, but it looks like the incidence of diabetes is slightly increased with the use of statins. The overall benefits of statins are enormous. It reduces the risk of cardiovascular disease and stroke by about 25%. That's why they are trying to get more accurate risk assessments and the PREVENT equations, I think, more accurately assess the current population.
Elizabeth: The projection that it's going to increase the MIs and the strokes if they are employed is concerning.
Rick: Well, it is, but again, these medications have risks. Now, here is what we need to do, Elizabeth. That 7.5% risk over 10 years -- that's what we defined as high enough risk that one needs to provide moderate or intensive therapy. The question is with this new equation maybe it's not 7.5%, maybe it's 6%. There is more information that needs to be derived from this to find out where is the proper cutoff and who will receive the most benefit and the least risk.
Elizabeth: I would also just respectfully remind you that this relies on two factors, at least, that I can identify. One is people coming forward to be evaluated in the medical system according to their individualized risk, and that relies on the presence of both primary care folks as well as cardiologists in order to take care of that whole population.
Rick: Yeah. One of the great values is, literally in about 30 seconds you can enter the information and it will give you the risk. It does assimilate all of the information together and I think it provides a more accurate risk assessment. With that, I think it enables our primary care to engage the patient to decide how aggressive they want to be with regard to preventive therapy.
Elizabeth: I'm going to say I bet we're going to be talking about this again.
Let's finally turn to Annals of Internal Medicine and this is a look at whether oral methotrexate is helpful for people with knee osteoarthritis. This is a study from the U.K. It's a multicenter, randomized, double-blind, placebo-controlled trial that was done in 15 secondary care musculoskeletal clinics.
They had a total of 207 participants with symptomatic radiographic knee osteoarthritis, and knee pain on most days in the past 3 months. These folks were randomly assigned 1:1 to oral methotrexate once weekly, with a 6-week escalation from 10 to 25 mg or a matched placebo over 12 weeks, and they continued their usual analgesia.
They also looked at imaging to see whether this had any impact on the appearance of the knee osteoarthritis. They were able to achieve follow-up in 86% of their participants and sure enough, the addition of methotrexate to the normal regimen of pain relief did result in a mean decrease in their knee pain score. They also improved with regard to stiffness and function. They did not notice any difference in the imaging that was related to taking methotrexate.
Rick: A couple of things about this particular study. There are people that just don't respond to nonsteroidal anti-inflammatory medications or other therapies that we have available. Since this affects over 360 million people globally and, by the way, the incidence is going up, it's important to have something that's effective.
A couple of things with this particular therapy. It did look like it improved things at 6 months, but at 12 months it lost some of the treatment effect. Concomitantly, they also decreased methotrexate dose between 6 and 12 months. It could be that it's not effective long term, or it could be just that they lowered the dose.
They did identify there was a significant treatment effect with those that had an elevated C-reactive protein. Remember, C-reactive protein is a sign of inflammation. The benefit of methotrexate may be related to affecting systemic inflammation and that's really what it does well. We might be able to pick a population that is most likely to receive benefit from it.
Elizabeth: I agree. Then, I would also note that I didn't realize that there were people who just really can't tolerate oral methotrexate.
Rick: There aren't very many. Besides side effects associated with it -- primarily GI side effects -- some people will have inflammation of the liver. There is a small number of individuals that don't tolerate it, but the vast majority of individuals do, and these are relatively modest doses.
Elizabeth: Well, I agree that there has got to be something that we can add to the armamentarium. But I think you're right. I think that we need more research on this particular strategy to see if it persists in its benefit.
Rick: Agreed.
Elizabeth: On that note then, that's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.
Rick: And I'm Rick Lange. Y'all listen up and make healthy choices.