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 a new agent for sickle cell, two ways to assess blood flow in the heart, the dangers of cosmetics for kids, and predicting who will develop dementia.
Program notes:
1:00 ED visits for kids due to cosmetics exposures
2:00 Fifteen-year study period
3:00 Need to store in a locked location
3:11 A new drug for sickle cell disease
4:11 Also received hydroxyurea in 2/3
5:12 Addresses the protein
5:40 Blockage in arteries around the heart
6:40 Fractional flow reserve
7:40 Could place a stent?
8:42 Predicting dementia with three tests
9:43 Ranged in age from 67 to 83
10:43 Thinning of brain
11:41 Somehow identify earlier
12:52 End
Transcript:
Elizabeth Tracey: Can we predict who's going to develop dementia?
Rick Lange, MD: Managing someone with coronary artery disease.
Elizabeth: A new targeted agent for sickle cell.
Rick: When kids and makeup don't mix.
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 21st, 2019.
Rick: And I'm Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso, where I'm also Dean of the Paul L. Foster School of Medicine.
Elizabeth: And we're recording in-person. It's so rare for us to do this, but what a gift because you're here doing your FDA thing.
Rick: Most of our listeners may not realize is when we typically record, you're in Baltimore and I'm in Texas, in El Paso. But today we get to meet in Maryland, just outside of Washington, D.C., so it's a real pleasure to actually do this in-person, Elizabeth.
Elizabeth: I agree. Gosh, it seems like it's been many years. So where shall we start? Why don't we start with the one that's getting a ton of media attention this week. That's a look at emergency department visits relative to children and their exposures to cosmetic agents, and this is in the journal Clinical Pediatrics, something that's totally new for us.
Rick: I thought this was really interesting and I'm glad that you identified it. You know, we spend about $62 billion annually in the U.S. in cosmetics. Per household, that's about $170. But this study did something that I've not seen before, a retrospective analysis using the National Electronic Injury Surveillance System that's in the emergency department and looked at kids under the age of 5 who were treated in the U.S. emergency departments over about a 14-year period for cosmetic-related injuries.
That kind of caught my attention because I'm thinking, "Cosmetic-related injuries?" But this is a huge problem, especially for kids under the age of 2 because 60% of the kids that they identified -- and they identified almost 65,000, by the way -- who presented to the emergency department after being exposed to cosmetics, either ingesting them or actually applying them topically.
So over this 15-year study period, what they found is that the commonly occurring injuries were related to nail care, hair care, skin care, and fragrance products. These things are packaged so nicely and oftentimes, they have these fruity smells that kids -- especially under the age of 2, but even all the way up to age 5 -- see them and actually will drink them or put them on the skin and get contact burns.
Elizabeth: I also saw, when I saw the coverage of this study, the American Academy of Pediatrics recommends that these things get stored just like pharmaceuticals.
Rick: Absolutely. In other words, oftentimes -- and we're all guilty of it, because these things are bottled in very attractive bottles -- we put them on the bathroom sink, or put them on the counter, or put them on the dresser where kids have exposure to them. Of course, they look attractive and the kids, in fact, do get access to them.
Oftentimes, they're just learning how to open these things and they're not childproof, and then about 90% of the things that they examined were actually poisonings related to that. And so storing these in locked cabinets so they're out of the reach of kids is incredibly important.
Elizabeth: Right, but we need to think about that. Of course, as we talked about before we started to record, this is the first time I've ever heard this.
Rick: Yeah. That's why I'm glad you picked this.
Elizabeth: Let's turn to the New England Journal of Medicine, some good news here, something that's called voxelotor, an agent for sickle cell disease. And I've shared with you before that in sickle cell disease I've seen people hospitalized in sickle cell crisis, and it just looks like excruciating suffering.
So I thought this was a good-news study. In this case, the basic defect that we see in sickle cell disease is deoxygenated sickle hemoglobin polymerization. So the stuff polymerizes and then it gets into those small blood vessels and occludes them, and causes all kinds of problems secondary to that. We also know that sickle cell disease can truncate somebody's lifespan as well.
In this study, they had 274 participants who were randomly assigned in a 1-to-1-to-1 ratio to receive one of two doses of this agent, voxelotor, either 1,500 mg once a day or 900 mg or a placebo. These were both adults and adolescents who were included in this trial. Two-thirds of them were receiving hydroxyurea at the same time, and they looked at these folks at baseline and at Week 24, and they said, "Hey, how are they doing?"
It turned out that the 1,500-mg voxelotor group did the best with regard to this hemoglobin issue. The 900-mg group did okay, and then the placebo group, of course, what we expected. There were adverse events in all of the groups, but the investigators say that they were largely related to sickle cell and not to the use of this agent.
Rick: And this has important implications [not only] for the 100,000+ people in the United States that have sickle cell, but the millions across the world. We actually have been trying to target the gene because we know what causes sickle cell. It's a change in the amino acid in the hemoglobin.
When the hemoglobin loses its oxygen, then it assumes an unusual shape that causes the red blood cell not to look like a plate, but to look like a sickle and it clogs up the arteries. This is a novel therapy because it doesn't address the gene. It actually addresses the protein and it keeps the protein from doing that abnormal folding. It's a once-a-day administration, and as you suggested, it was very effective in terms of preventing some of the sickling.
Now what they didn't do in this study was they didn't extend it long enough to see if it can decrease the number of sickle cell crises that you mentioned, but that's the next phase of this study. At least in the first part, it does look like it affects the protein in a favorable way and the next question is can they actually avoid some of the sickle cell crisis that you mentioned.
Elizabeth: Since we're in the New England Journal of Medicine, let's turn to your area of expertise. Go ahead.
Rick: We're talking about people with coronary artery disease or blockage in the arteries around the heart. There are several ways to treat that. Obviously, we try to prevent a heart attack and we do that by giving various medications that prevent platelets from clumping.
But in some individuals, there's the suggestion that if we actually revascularize -- that is if we fix the blockage in one way or another -- that it can actually improve their survival. Now that's not everybody, but it's in some individuals that have significant blockages.
Now one of the most common ways it's identified is to do an angiogram on somebody. That's an invasive procedure where we take a look, and if it's a really tight blockage -- like 90% -- and it's associated with symptoms, then oftentimes that's treated with a stent or bypass surgery. If it's a minimal blockage, then we just treat it with medications. But in the intermediate range, sometimes it's confusing what to do.
In that invasive procedure, we can put in a small little catheter and measure the blood flow at rest and when we try to increase the blood flow. That's something called FFR or fractional flow reserve.
Well, we'd like to be able to do that in a noninvasive way. Recently cardiac MRI can allow us to actually measure blood flow at rest and when we try to increase blood flow to see if, in fact, it increases appropriately. Now the question is, is that as good as the time-honored invasive way?
That's what this study did is it compared the two, and they did that in 918 patients that had known coronary disease and also were considered to be at high risk -- they had diabetes or smoking or hypertension or high cholesterol. They randomized them to FFR, the invasive way, or to using cardiac MRI. They followed them over the course of a year. What they discovered was between the two groups, there was no difference between the two strategies.
Now the nice news is, because the newer strategy is noninvasive, it carries less risk with it and it can be more widely available as well. So this noninvasive way, the cardiac MRI measuring perfusion, was shown to be noninferior to the traditional invasive way.
Elizabeth: But the invasive way, the advantages to that would be that you could go ahead and place the stent if you needed to?
Rick: Well, that's one advantage or you might take the other tactic and say, "Listen. If we can avoid doing that, if the cardiac MRI avoids doing that if it's unnecessary, then you don't expose the person to an invasive procedure." In fact, those that were randomized to FFR, virtually 100% of them ended up having angiography. Those that had the cardiac MRI, less than 50% did, so it saved them from having an invasive procedure. And it did that without increasing the risk for having a serious cardiac event.
Elizabeth: Hmm, so would you call this practice changing?
Rick: Yeah, I think it can be. Again, when you're talking about cardiac MRI, the technical term is magnetic resonance perfusion. It certainly provides another option for individuals.
Elizabeth: And you think it would be more widely available, also.
Rick: Anybody that has an MRI machine with certain software. It doesn't require a cardiac cath lab. It doesn't require the special techniques, for example, that I learned as an interventional cardiologist, but it can be done by a radiologist, for example, or a cardiologist with expertise in cardiac imaging.
Elizabeth: Let's turn to the Journal of the American Medical Association, and this was a group of three different kinds of tests that were used to assess people who did not have dementia at baseline, but in order to predict whether or not they might develop dementia over the followup. In this case, what they used were they labeled this thing AT(N) for amyloid tau and neurodegeneration biomarkers.
They had a cohort of people without dementia age 60 years or older. This was 480 people in the Mayo Clinic Study of Aging. They had a clinical evaluation and amyloid PET scanning, tau PET scanning, and MRI, cortical thickness measurements between April 2015 and November 2017, and at least one other clinical evaluation follow up by November 12th, 2018 -- 4.8 years of follow up.
Their primary outcome was a composite memory score at 15-month intervals, and this whole group ranged in age from 67 to 83 years. So during that time, they were able to use this particular set of assessments to say that they could predict just with a little bit more accuracy who was going to end up developing dementia over the follow-up period. They do admit that the clinical importance of this difference is unclear at this time.
Rick: Right, and so, we know that there are some baseline things that can help predict who might develop dementia. For example, does someone have mild cognitive impairment to begin with, or do they have an APOE abnormality? That's a genetic abnormality. Those that have those are more likely over the next 5 years to develop dementia.
Do these biomarkers actually add additional predictive value? As you mentioned, they do, but it's really modest and it may not be particularly helpful. And that's disappointing, because of the three biomarkers, amyloid and tau are thought to be fairly specific for Alzheimer's. The (N), the neurodegeneration, is an evaluation looking at thinning of the brain, and it was thought that if you combined all three of these things it would provide some additional information.
Elizabeth: Yeah, modest, at best. The editorialists say it could be useful in clinical trials.
Rick: Right. When we have someone older and we're trying to see does a drug prevent dementia, what you'd like to do is identify those individuals that are at high risk. Now in the group using those three tests, they were able to combine those three and say, "There are certain groups that seem to advance faster than others, and those are the ones we would target with new therapies."
So you're right. These things can help identify individuals that are more likely to progress faster, but in general in the large population, they don't add a whole lot more than our clinical and our genetic information.
Elizabeth: I think we need to frame up this particular study within the context of disappointing results for trials that have attempted to reduce amyloid in the brain, and that hasn't really resulted in any significant prolongation of the interval during which Alzheimer's disease develops. And so everyone is speculating, "Gosh, if we could just somehow identify these folks earlier and intervene earlier, maybe some of these things would work out."
Rick: Right. That's why they looked at these biomarkers to say, "If we have these things, even before someone develops dementia, can they help us predict?" But as you mentioned, targeting amyloid protein hasn't been particularly helpful to date, so we're still looking for that Holy Grail, both identifying individuals and then how do we interrupt that process?
Elizabeth: Well, and we still haven't really answered the question of whether it's amyloid or tau or neurofibrillary tangles. All of those things are present in people who are cognitively normal.
Rick: You're right. In other words, the presence of those don't guarantee that you'll have dementia. It certainly raises the risk as well, and that leads to speculation that maybe it's something else that's actually causing the amyloid or tau and we just haven't gone back far enough to figure out what that is. So stay tuned. There's still a lot to learn here.
Elizabeth: Indeed, but we're looking. On that note, 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.