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USPSTF Backs New Options for HIV Prevention; Occupational Radiation Exposure

— Also in TTHealthWatch: extracranial-intracranial bypass for stroke

Ƶ MedicalToday

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 HIV prophylaxis, bypass surgery in the head to prevent stroke, cancer risk in occupational radiation exposure, and proteomics and cardiovascular risk.

Program notes:

0:40 USPSTF guidelines for HIV prevention

1:40 Was associated with decreased risk

2:40 Injection every 2 months

3:40 Potential benefits of RNA screening

4:11 Extracranial-intracranial bypass

5:11 Didn't differ from medical therapy

6:03 Cancer mortality after low dose radiation

7:05 Individual monitoring data

8:05 Previous studies from nuclear blast

8:51 Proteomics and CVD

9:51 Retrospective data

10:51 Already have many models

11:43 End

Transcript:

Elizabeth: An update to preventing HIV transmission.

Rick: Can proteins in the blood predict cardiovascular disease?

Elizabeth: What's the cancer risk relative to low-dose radiation exposure?

Rick: And if people at risk for a stroke, can bypass surgery in the head actually prevent stroke?

Elizabeth: That's what we're 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 to JAMA first? We got quite a bit of information from there this week. I'd like to talk about the USPSTF's guidelines relative to preventing HIV transmission in those at risk. There is a strategy -- so-called pre-exposure prophylaxis, or PrEP. This involves, of course, taking medications in those who are at risk for acquiring HIV infection in order to prevent its successful establishment. That's, of course, from the virus' perspective.

The last time these folks looked at this was in 2019. At that point, there was only one oral medication that was available. Now, we've got two additional ones and it was time to take a look again at what was going on. As is their wont, they looked at 20 randomized clinical trials with about 36,000+ folks and 12 studies of diagnostic accuracy -- over 5 million participants in this -- and basically said, "Yes, indeed, in adults who are at increased risk for HIV acquisition, oral PrEP was associated with a decreased risk of acquiring this infection compared against placebo or no PrEP." Then there are two oral preparations -- they're non-inferior to each other -- and an injectable medication that's one of the two that was recently approved, actually reduced the risk of HIV infection, compared with the oral, in the populations that they were able to study.

The editorialist, who is truly excellent, says, "Is the fact that there are more choices available now going to enable us to have a greater impact, since the objective in the U.S. is to reduce new HIV cases by 90% by 2030?"

Rick: Elizabeth, these new choices do provide benefit. There is no question about it. For example, the original oral regimen shouldn't be given to people that have a depressed kidney function. It shouldn't be given to people with osteoporosis. Whereas the newer oral agent, it can be administered to those individuals, albeit it has different side effects. Obviously, injectable means you just have to get an injection once every 2 months. You don't have to take an oral therapy.

Unfortunately, that's not going to solve some of the disparities. For example, just a couple of years ago when they looked at it, 78% of White persons that were expected to benefit from this pre-exposure prophylaxis actually received it, compared with only 11% of African American persons and 21% of Hispanics. That has nothing to do with the oral medication or availability. That really has to do a lot with education and making it available. So the availability of different regimens is really helpful, but it's not going to solve that problem.

Elizabeth: No. The editorialist also notes that the CDC now recommends discussing PrEP with all sexually active adults and adolescents as one means to address this issue of disparity. The other thing that they are saying is recommendations for both an HIV antigen/antibody and HIV RNA assay for individuals with recent exposure to oral or injectable PrEP. They do talk about potential benefits of RNA screening. However, it's also really expensive.

Rick: Right. That really shouldn't hold up the use of PrEP. What they are trying to do is diagnose early HIV infections and begin to treat it, especially if you're going to use the injectable form of PrEP, because people can develop resistance. What the editorialists say is, "Let's not put any barriers into getting PrEP available" and that could be one of the barriers.

Elizabeth: Very good. Staying in JAMA then.

Rick: I teed this up as, "Can we do a bypass surgery in the brain, or actually in the head, to prevent stroke in people that are at risk of stroke?" This is called an extracranial-intracranial or EC-IC arterial bypass. It could be performed on people that have had an occlusion of either their internal or their middle cerebral artery. Those individuals, if they haven't had a large stroke, are at risk of having one because they have decreased blood flow to that part of their brain. They may have very mild symptoms.

Several studies have already looked at this and, unfortunately, despite the fact it sounds like it ought to work, it hasn't in the past. But our surgery has gotten better and so this is a re-look at that, asking whether this EC-IC bypass can prevent risk of stroke and death in the patients with symptomatic arterial occlusion.

The study was done in 13 centers in China with 324 patients. Half of them received medical therapy. The other half received the EC-IC bypass. They followed them for the first 30 days to see whether they could prevent stroke and death, and then over the course of 2 years. What they discovered is there was no significant difference in the risk of stroke or death regardless of whether they did bypass surgery or they used medical therapy.

You say, "Well, why is that because the surgery is better?" Well, that's because our medications are also better. We're using potent antiplatelet agents; we're using statin therapy, lifestyle modification, and all those things contribute to a lower risk as well.

Elizabeth: I have actually watched this surgery and it's really quite dramatic and it also makes sense to me that, gosh, if we can use a bunch of medications, which we certainly are seeing in lots of other arenas, why not do that versus doing this rather dramatic operation?

Rick: If the operation was helpful, we'd submit individuals to it. But it's interesting because in the first 30 days the risk of stroke with the operation is about 6% and without the operation with medical therapy it's only about 2%. That means 98% of individuals in the first month after having symptomatic occlusion of their internal or middle cerebral artery actually do pretty well. Now, over the course of 2 years it evens out, but again there is no benefit of doing surgery.

Elizabeth: Okay. Let's turn to the BMJ and this is a look at cancer mortality after low-dose exposure to ionizing radiation in workers from France, the U.K., and the United States. It's called the INWORKS cohort study. I think this is a really interesting study in view of the fact that Japan has decided that they're going to start releasing some of the water from the Fukushima reactor and this is unquestionably going to be exposing more people to radiation.

The authors note that the public's exposure to ionizing radiation has increased in recent decades. Taking the U.S. as an example, they say the average person's annual effective dose doubled between 1985 and 2006, and has remained elevated since. That's primarily due to increases in exposure from medical imaging procedures.

This is a look at a lot of workers in the nuclear industry in the thee countries that I mentioned -- over 300,000 of them, with individual monitoring data for external exposure and a total follow-up of almost 11 million person-years. I learned something new, which is this unit of exposure now is called a gray, abbreviated Gy, versus a rad, which is what I was familiar with before.

They showed over this 10 years of follow-up 103,000+ deaths, of which 28,000+ were due to solid cancers. They estimate that the rate of mortality due to solid cancer increased with cumulative dose by 52% per Gy or gray, lagged by 10 years. So it seems like, even though we have all kinds of things in place to protect people from ionizing radiation in the workplace, that that exposure is still problematic.

Rick: The virtue of this particular study is it's the first one to actually look at low-dose ionizing radiation. The previous studies we have primarily looked at fallout from the nuclear blast in Japan. This is a large number of individuals followed up over 70 years and they have a chronic kind of low-dose exposure.

Now, the risk is low in these individuals, but it still increased it nevertheless, primarily solid tumors, providing evidence that we should use the minimum allowable radiation dose possible. Now, that's not only for workers, but we'll also talk about for radiation studies as well. For individuals that are having radiographic studies, the older you are, the less cumulative dose you have. If you start these studies at an early age and continue on, then you increase exposure.

Elizabeth: A word of warning. Let's turn to your final one that's looking at proteomics and cardiovascular events. That's in JAMA also.

Rick: We've talked before about risk stratification. If you take someone that doesn't have any underlying cardiovascular disease, can you predict who is at risk? Because those individuals we really want to target for either lifestyle changes or for medications that could lower that risk. We know there are clinical risk factors. Things like age, gender, the presence of high blood pressure, diabetes, and kidney disease.

We've talked before about the fact that there are some genetic differences in individuals that may predispose them, called genomics. Well, there is also this whole field called proteomics and these proteins can be measured in the blood. They assess both the genetic diversity, but also many environmental factors and ongoing biologic processes. The question is, now that we have new technologies that allow us to measure thousands of these in a relatively short period of time, can we use that information to predict who will have cardiovascular disease?

They developed a protein risk score using more than 4900 protein levels in the blood to see whether they can predict major atherosclerotic cardiovascular events like death, stroke, and heart attack. This is a retrospective study of over 13,000 individuals in whom they had proteomic data and, again, no previous cardiovascular disease. In the 16 years of follow-up, the proteomics data provided a little bit of information, but it was really pretty modest. I mean, most of the information is contained in the clinical risk score.

Elizabeth: I think this whole notion of examining the proteome is like trying to catch water with your hands. It's such a moving target and one's proteomic profile changes moment-to-moment, let alone month-to-month or year-to-year. So it's unclear to me how something like this could actually be beneficial.

Rick: Elizabeth, your point is well taken. The genetic information stays the same, but the proteomic information varies -- again, not just upon the genes, but upon the environment and lifestyle changes as well. It may not be a single measurement, but some measurement over a period of time. You're absolutely right.

Elizabeth: Tell me what your view is on whether we really need additional stratification of risk for people when we already employ so many models.

Rick: The nice thing is most of the information is contained in clinical factors, which are very readily available to the primary care provider, but also to the patient as well. It's oftentimes not that we don't have enough information. We just don't act upon the information we have.

I mean, how many of us are still overweight or don't exercise, or don't eat a healthy diet, or don't have routine checkups, when we know that all of those things can actually decrease the risk of cardiovascular events? If this was a big jump, we could recommend it, but it's actually a very modest improvement over the clinical risk factors. So that's where I would put most of my attention.

Elizabeth: Okay. 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.