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Preventing Type 1 Diabetes; Testing for HIV: It’s PodMed Double T!

PodMed Double T is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, 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. A transcript of the podcast is below the summary.

This week’s topics include preventing Type 1 diabetes, diagnosing meningitis and encephalitis, white coat hypertension and CVD, and screening and prevention of HIV infection.

Program notes:

0:45 A correction

1:25 White coat hypertension and cardiovascular events

2:25 Treated rise in blood pressure

3:25 Increased risk by 36%

4:21 USPSTF recommendations for HIV prevention

5:21 Pre-exposure prophylaxis

6:21 Now will be covered by Medicaid

6:49 Prevention of type 1 diabetes with an antibody

7:49 Transient drop in white blood cells

8:49 Delayed by 2 years

9:58 Diagnosing encephalitis and meningitis

11:00 Confirm with more specific tests

12:34 End


Elizabeth Tracey: Does so-called white-coat hypertension increase the risk of cardiovascular events?

Rick Lange, MD: Using gene sequencing to diagnose meningitis.

Elizabeth: Can we prevent type 1 diabetes in those at risk?

Rick: And recommendations for screening and preventing HIV infection.

Elizabeth: That’s what we’re talking about this week on PodMed TT, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a medical journalist at Johns Hopkins, and this will be posted on June 14th, 2019.

Rick: And I’m Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso and also Dean of the Paul L. Foster School of Medicine.

Elizabeth: Recently returned from France, of course, and we do have a correction that we’re going to give today.

Rick: So Elizabeth, we appreciate our listeners, first of all, being involved with the podcast, but also to hear something that’s a little bit odd, a little bit different, or a correction is communicating that to us. Over the course of the 14 or 15 years we’ve been doing this, we’ve probably had two or three. I want to appreciate a listener that contacted us just before I left for France about treatment for asthma. Elizabeth, I’ll let you talk about the correction.

Elizabeth: Yeah, so the correction was we were just talking about the different types of meds that are used to manage asthma, and instead of saying, “Antagonist,” you said “agonist.”

Rick: Right. Ed, thanks for pointing that out, and with this correction, we’ll move on to the newest studies for this week. Elizabeth, where do you want to start?

Elizabeth: Let’s turn to Annals of Internal Medicine, taking a look at this issue of white-coat hypertension. As we’re all aware, there’s been a lot of energy behind the idea that people really need to take measurements of their blood pressure when they’re not in a physician’s office, so-called ambulatory blood pressure. And this is made a lot easier by all the plethora of devices that are out there right now. That’s what the idea and the recognition that when somebody comes into a physician’s office and they sit down and get their blood pressure measured, it can often be elevated. And the question is, “Well, all right, if it’s elevated when it’s in the office, is that necessarily problematic?”

This is a meta-analysis where they took a look at 27 studies with almost 26,000 participants who had either what they called “untreated white-coat hypertension,” which they abbreviate WCH, or treated white-coat effect, WCE. That was a new term for me. I was unfamiliar with that, which is somebody who has treated hypertension, but oops, they get a little rise, a transient rise when they come into the office. And so they took a look at these blood pressure, what they call phenotypes, and then also clearly there are two others: those people who don’t have hypertension in or out, not receiving any kind of blood pressure meds; and normal in-office and out-of-office, but receiving high blood pressure meds.

Basically, at the end of the day, what they found was that gosh, those folks who had white-coat hypertension are at increased risk for cardiovascular events and cardiovascular mortality, so suggesting that what we really need to do is make sure we take those ambulatory measurements because they can be really informative. Those people who came in and had that transient rise, the white-coat effect, but were being treated, had no increased risk of a cardiovascular event.

Rick: This was a significant increase in cardiovascular events. People that had white-coat hypertension, untreated, it increased the risk of these events by about 36%, increased their all-cause mortality by about 33%, and their cardiovascular mortality by about 200%. Where it seemed to matter most were in those people that were older, over the age of 55. We know that those people oftentimes have multiple risk factors for cardiovascular events as well. So as you suggested, the combination of in-office blood pressure measurements followed by outpatient blood pressure measurements is really the key to making sure that we both make a correct diagnosis and also treat the hypertension appropriately.

Elizabeth: I’m wondering about the significance of white-coat hypertension in people who are younger, because we certainly hear lots and lots of reports of that.

Rick: In this particular study, when they looked at those under the age of 55 and those that did not have other cardiovascular risk factors, then they weren’t at an increased risk of cardiovascular events.

Elizabeth: So those ambulatory measurements, then, are really important, folks. Think about it. Let’s turn to one of yours. How about this in the Journal of the American Medical Association issue of HIV prophylaxis?

Rick: This is another recommendation from the USPSTF. For those listeners that may not be familiar or joining us as new listeners, this is the U.S. Preventative Services Task Force, and it’s an independent volunteer body. It’s supported by governmental funds, but its recommendations are completely independent and not influenced by the government. And it’s charged with looking at the current evidence to talk about preventive measures — in this particular case, how to prevent HIV infection. They looked at, “Should we be screening for it?” and then secondly is prevention. Let’s talk about each of those.

They found very good evidence that people between the ages of 15 to 65 and all pregnant women should be screened for HIV. Now they didn’t talk about how often that should be repeated. It probably should be repeated in individuals that are at high risk for developing infection. The second thing they talked about was preventing it, taking what’s called pre-exposure prophylaxis. And they found very good evidence for this, by the way, particularly individuals that are at high risk. Men who have sex with men, they have a sex partner who is HIV positive, they have inconsistent use of condoms, or they’ve had a sexually transmitted infection like syphilis or gonorrhea or chlamydia within the last 6 months. That’s the first high-risk group.

The second highest-risk group is heterosexually active women and men who also have had one of those characteristics I previously mentioned. Then, finally, people who inject drugs and either share their drugs or there’s risk of sexual acquisition related to the drug use. Those individuals should receive pre-exposure prophylaxis with HIV medications. And how effective are they? They’re really effective. By their estimate, there are about 1.2 million individuals in the U.S. who should be getting pre-exposure prophylaxis, yet only about 10% are.

Elizabeth: With regard to barriers, then, to people choosing to go on PrEP, I know that cost is one of those things. Was there any identification of other barriers in this particular recommendation?

Rick: They didn’t identify them, but you mentioned that cost is one of the factors. Because this is now a recommendation from the USPSTF, this should be covered by Medicaid now. So even individuals that normally wouldn’t have access to it and they’re on Medicaid, can receive the medication.

Elizabeth: This is really good news. Of course, it also begs the question of people really need to go and be tested.

Rick: Also, this information needs to be in the hands of the healthcare provider so they can take a good history to see if a person is in a high-risk category.

Elizabeth: OK. Let’s turn to the New England Journal of Medicine. This was a look at something I thought was pretty exciting, the idea that in people who are at risk to develop type 1 diabetes, it may be possible to use an antibody in order to reduce their risk or prolong the duration of time until they actually develop it. It turns out that there’s 1.25 million Americans who have type 1 diabetes, and most current thought on this indicates that the pathogenesis of the condition is thought to be, “Hey, you have a genetic risk,” but there are environmental factors that initiate this autoimmune destruction of the beta cells in the pancreas.

In this case, they used an antibody and they had two groups, one of whom received it, one of whom didn’t, of course. New onset type 1 diabetes rates in the people who got the antibody were about 15% per year in comparison to almost 36% per year in those who got the placebo. They did have an issue with their lymphocyte counts because of treatment, but they were able to rebound after a fairly short period of time. They also were able to identify really beautifully these types, these subgroups, who would benefit from this particular treatment.

This study was really small. There were only 76 participants, and they only had one 2-week course of treatment. I interpret this study as exciting evidence that we might actually be able to interrupt that whole autoimmune process that results in frank type 1 diabetes and its whole constellation of negative impact on someone’s life.

Rick: I agree with you. I’m not sure this particular antibody is the panacea, but it is a proof of concept. Type 1 diabetes is an autoimmune disease mediated by T cells, those particular inflammatory cells. By the way, this antibody was to those T cells.

By affecting the immune system or doing immunomodulation, they were able to delay the diagnosis of diabetes for 2 years in these individuals, so a couple things. One is this was just a single treatment with an antibody. Even though they just got it one time, the effects lasted for years and that’s going to open the door to other medications or other pathways to try to affect this. This particular medication runs the risk, you said, of decreasing the white cells. It causes a rash. It can activate other viral infections that have been dormant like a CMV or a herpes simplex virus, but as a proof of concept, it’s really important.

Elizabeth: I think this is also really exciting because they were able to identify that these were folks who were at risk based on siblings and family history of having type 1 diabetes. What it suggests to me is that ultimately we may be able to discern that up front when a child is born that they may have this constellation of genetic characteristics that put them at risk and start it even with that.

Rick: That’s an interesting hypothesis because you’re talking about a lifelong treatment initiated even before symptoms begin. What we know is depending upon the genetic risk factors, as many as 50% to 75% of individuals with those risk factors with a sibling that’s already had diabetes was likely to develop it. Those particularly high-risk individuals are most likely to benefit.

Elizabeth: Let’s remain in the New England Journal of Medicine and turn to yours.

Rick: So Elizabeth, this was a fascinating study trying to diagnose what the cause is for people that develop meningitis, an infection of the surrounding of the brain and through the spinal cord and also encephalitis, that is an infection of the brain. About 50% of the time, even though people develop meningitis or encephalitis, we really can’t figure out the cause. And that’s because the routine way we do it is you examine the patient, you take a history, and you say, “I think these could be the organisms that are doing it,” and you test for specific organisms. But if you don’t happen to get the right organism or let’s say it’s an inflammatory process, then you’ve missed the boat.

So what these authors did was they actually used a clinical metagenomic sequencing process. Wow! They took a sample of the cerebrospinal fluid. They did gene amplification, isolated the particular DNA and RNA, took out any of the DNA or RNA which was thought to be due to the host, then submitted it to analysis to say, “OK, does this DNA or RNA match up to any particular organisms?” It could be a fungus, could be a bacteria, or could be a virus.

If they did that, they would try to confirm it with more specific tests. Of 58 different infections in 57 individuals, 33% were diagnosed by conventional testing and this metagenomic sequencing, 45% by the conventional testing alone, but 22% or 1 in 5 were identified by the metagenetic testing and not by conventional testing.

Elizabeth: Right, a really terrifying infection, I would say [laughter] at least from my seat in the bleachers. I’m wondering two things. One thing is how long does it take in order to do this analysis, especially the confirmation? And the other thing is can you see a time when this might actually replace the traditional means of making the diagnosis?

Rick: Two great questions. But first of all, it takes about 90 hours to have this test done. Will that time be shortened with additional technologic advances? The answer is probably yes. I don’t think it will replace — I think it will supplement. Let’s say the infection has been cleared and all you have is antibodies to that infection to make the diagnosis. That’s oftentimes what happened here is the infection had already cleared, but conventionally we can test antibodies and say, “There’s an antibody to this infectious agent. That must have been the cause.” But since the infectious agent isn’t there, we can’t look for any genetic material for it. Will it provide an answer sometimes conventional testing doesn’t? Yes. And now we need to figure out how to best integrate it into our conventional testing.

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.