TTHealthWatch 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 inhaled interferon for COVID, dropping measles vaccination rates, a polypill to reduce cardiovascular disease, and the utility of masks.
0:50 Antiviral therapy via inhalation
1:42 Didn’t improve hospital discharge
2:46 How is it delivered?
3:00 Use of masks to reduce COVID transmission
4:03 Did not result in 50% reduction in infection rates
5:01 Significant limitations to study
6:02 Will it be used to deny masks?
6:26 Polypills in those without cardiovascular disease
7:28 Higher risk of low blood pressure
8:28 Keep people from getting any therapy?
8:52 Measles vaccination rates
9:54 By 2019 rising again
10:51 Increased 567% in 2019
11:50 Trust issues in different countries
Elizabeth Tracey: What’s going on with measles vaccination worldwide?
Rick Lange: A nebulized antiviral agent to combat COVID.
Elizabeth: Does a Danish study really tell us anything about the utility of masks?
Rick: And what’s a polypill and how can it be used for cardiovascular disease?
Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I am Elizabeth Tracey, a Baltimore-based medical journalist.
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: In keeping with what we’ve been doing the last several weeks, Rick, I’m going to ask you to start. Which would you like to choose?
Rick: Elizabeth, let’s talk about this nebulized antiviral agent used for COVID infection. This is an antiviral therapy that’s designed to be given inhaled — nebulized — because, as we’re aware, the COVID virus primarily affects the nasal pharynx and the respiratory tree. We can actually give an antiviral agent to a higher level in those areas without the toxicity associated with giving it intravenously.
This is the use of beta interferon. It’s known to be a cytokine that modifies the immune system. There were 101 patients randomly assigned to either a single daily nebulized beta interferon or a placebo. These were people that were in the hospital, about two-thirds of them on supplemental oxygen.
They followed them over the course of 14 days — that’s the duration during which they received either the nebulized interferon or a placebo — with the intent of seeing if they improved clinically. Those that received the nebulizer were twice as likely to end up with really no significant symptoms at the end of the 14-day period.
Now, it was a small study. It was underpowered to detect whether it improved mortality and it didn’t improve hospital discharge, but it actually did improve resolution of symptoms in those who received it.
Elizabeth: Let me just say this is in the Lancet Respiratory Diseases. Tell me about your thoughts on inhaled therapies for this particular disease, and also there has been a rather disappointing set of results, I would say, relative to beta interferon.
Rick: Most the time it’s given intravenously. To get to the high enough doses that you really need, it requires such a high dose there is a lot of toxicity associated with it. The advantage of the nebulized treatment is that you can give a large local dose to the area that’s affected without all the systemic manifestations. Again, this is a very early study. We need larger phase III trials, but the local application via nebulizer is much more attractive to give it intravenously.
Elizabeth: Yeah, I get that. I am just also a little bit, hmm, skeptical, if you will, relative to the benefits of interferon because other trials have been disappointing.
Rick: It probably has to do with a couple things. It may have to do with the individual syndrome that you’re treating, when do you give it, early in the disease or later in the disease, and how was it delivered as well.
Elizabeth: Certainly, we’ve seen other strategies and other therapies that are inhaled that seem to be pretty effective also, so I guess we’ll see more of that. Let’s turn to Annals of Internal Medicine. I said, “Does this study really tell us anything about the efficacy of masks?” This is a Danish study. It was conducted in Denmark between April and May of 2020. They recruited people who spent more than 3 hours per day outside their homes, but without occupational mask use.
They had an intervention group and a control group. In their intervention group, they provided them with 50 surgical masks and instruction on how to use them properly. Their primary outcome measure was SARS-CoV-2 infection in the mask wearer at 1 month. They used antibody testing in order to assess that primarily, but they also had PCR or hospital diagnosis.
They had actually more than 3,000 participants assigned to wear masks and just under 3,000 were controls. Of that number, just under 5,000 completed the study. They basically found that surgical masks in supplementation to other public health measures that were in place in Denmark during this time to reduce the spread of SARS-CoV-2 did not result in what they were hoping for, a 50% reduction in infection rates. This was a little bit disappointing.
Now, let me turn to the editorial which was written by Tom Frieden, the former director of the Centers for Disease Control and Prevention, who points out that there is a lot of things about this study that probably are not really very applicable to larger situations.
When I read through this, primary among those was the fact that compliance with mask-wearing was less than 50%, so it’s pretty hard to say, “Hey, it works” or “It doesn’t work” if you’re only using it half of the time.
Other factors that were also corrosive relative to the results of the study or the conclusions of the study were the fact that at that time the rate of transmission among community-dwelling folks in Denmark was low. Tell me what your thoughts are on this and how it got published in Annals of Internal Medicine.
Rick: Elizabeth, I agree. I think the study has very significant limitations. What they set out to ask was if you do all the social distancing, does the addition of masks provide additional benefit? Unfortunately, at the end of the study, we don’t have any answers to that. As you said, the transmission rate was low. The mask use wearing was low. The use of antibody testing is a particularly bad way of figuring out whether someone had infection or not, and by the way, a significant number of people that they enrolled in the trial didn’t even complete it. For all those reasons, I don’t think it really gives us any information.
By the way, I wouldn’t have published this because I think the study is a very poorly done study, but most of us have preconceived ideas about what works and what doesn’t. We think masks work, and to be able to publish an article that says, “Well, we’re not quite so sure,” it’s a little courageous to do that. I applaud them because you don’t want to not publish stuff because it doesn’t meet with your preconceived ideas.
Elizabeth: Yeah. I would say that in the current climate, particularly here in the U.S., this is the kind of study that it concerns me that someone’s going to seize on it and say, “Hey, this is abundant evidence that masks don’t really work and I don’t want to wear it.”
Rick: I agree with you. Someone may misconstrue this. That’s why I appreciate Tom Frieden writing that editorial that says, “Hey, guys, this doesn’t really answer the question, so you really can’t rely upon this to justify not wearing masks.”
Elizabeth: Okay. On that upside, I’m going to accept that. Let’s turn to the New England Journal of Medicine. This is yours, this abundant evidence that polypills are actually okay in people without cardiovascular disease.
Rick: I must say I’m skeptical of using polypills, and you say, “Well, first of all, what is a polypill?” That’s a pill that has a number of different ingredients — all at a regular dose. This particular polypill that was studied has a statin, a couple of medications — three — to lower your blood pressure. You could potentially combine them in a single pill that could lower cardiovascular risk in individuals that have never had cardiovascular disease, but are at increased risk of it, and that’s exactly what this study addressed.
It took almost 6,000 participants who didn’t have any evidence of cardiovascular disease, but they were at increased risk based upon their age, gender, and underlying conditions, and they randomized them to either a placebo, or to a polypill, or to the use of aspirin, or to both of those together. Use of a polypill plus aspirin reduced the risk of cardiovascular disease by 31% over the course of 4½ years.
A couple of caveats. There was a higher risk of hypotension and dizziness in this group. Before they got the polypill, they had a run-in phase — that is, they tested it first to make sure that people could tolerate it and would take it. What they discovered in that initial run-in phase about 15% of people either couldn’t tolerate it or wouldn’t take it, but those that actually completed the trial, there was a significant benefit to the use of a polypill plus the use of low-dose aspirin compared to placebo.
Elizabeth: I think this sounds like a great strategy for people in developing countries, and potentially even here in this country where we are concerned about the cost of prescription medications and just how onerous it can be to be on multitudes of medications and try to remember your scheduling, and dosing, and all that sort of stuff.
Rick: The advantage of this is it’s all in one pill. People take it once a day. It’s less expensive. You can manufacture this pill for $15 a month in India. The downside is it doesn’t allow you oftentimes to optimize, “We want to get the blood pressure down to a certain level, or cholesterol down to a certain level.” If that’s your goal, the polypill’s not the answer. But if that’s going to inhibit or prevent people from getting any therapy at all, polypill can be useful.
Elizabeth: I would just add that I’m going to look forward to more long-term data on this particular strategy to see whether addressing all of them at one time simultaneously with just a single medication is going to achieve the outcomes we’d like to have.
Rick: All right, Elizabeth. Let’s go to your next one. We’re talking about global therapies and global treatments.
Elizabeth: This is a little bit disappointing from Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention, “Progress Toward Regional Measles Elimination Worldwide between 2000 and 2019.”
I just want to remind the majority of our listeners that measles is really a pretty miserable disease and it is associated with mortality. The other thing that I think is really noteworthy about measles is just how very contagious it is and right now we’ve got this pandemic screaming along of COVID-19. Measles remains in environments — everybody catches it if somebody is shedding measles viruses, and so this, I think, is a particularly dire situation.
They were looking at what’s going on since, as I said, 2000 to 2019, and worldwide it was really looking pretty good. From 2000 to 2016, they actually saw that the incidence of measles declined, declined, declined until 2016, but by 2019 it was on the rise again.
As we know, this is a vaccine that requires two doses and so they divide the data into, “Hmm, how many kids get the first one and how many get the second one?” Unsurprisingly also, I guess I would note, the number who get the second one is lower than the number who got the first one. But worldwide, again, we’re seeing this very disturbing decrease in the number of kids who are even getting the first dose.
There are certain countries, of course, and that also is somewhat predictable, that are experiencing more of this than other ones — many of them in the developing world — but actually here in the U.S. we have pockets of people who are vaccine deniers and who are not getting their kids immunized, and we’ve had noteworthy outbreaks that we’ve actually reported on.
From 2000 to 2016, annual measles incidence decreased 88% and then increased 567% in 2019. How about mortality? They say measles vaccination prevented an estimated almost 26 million deaths globally since this program has been incepted.
I have this big concern about this decline in measles vaccination that’s going on right now. Similarly, we’re also seeing that with other routine immunizations worldwide and my concern is that we’re going to see a resurgence of infections like this.
Rick: To me, the numbers were pretty striking, just since 2016 the global measles mortalities increased almost 50%. It’s a failure to vaccinate, and particularly among the younger and older groups, that is those that are most likely to have mortality as well.
When you dig underneath a little bit, there are several things. You mentioned one, is that people get the first vaccine and don’t get the second. Some of that has to do with delivery and with storage. Some of it has to do with trust, by the way, and when they looked at different countries, there were some groups that were less willing to take up the vaccine because of concerns either about the safety or about why it was being given as well.
Access to services is an issue, social influences affect the confidence and motivation to receive the vaccine, and then there are strategic issues. They are different for different countries, by the way.
Elizabeth: Well, I think that this calls out a need to develop a comprehensive vaccination strategy because I believe that, as our coronavirus vaccines start to get deployed also, we’re going to need to confront vaccine hesitancy on the part, especially, of parents and figure out how we’re going to get everybody to say, “You know, these are public health success stories and we really need to make sure that we support this practice.”
Rick: In fact, Elizabeth, the WHO and other groups have actually outlined strategies called the Immunization Agenda 2030 and the Measles Rubella Strategic Framework 2021 to 2030 to address some of these issues that you mentioned.
Elizabeth: On that rather sobering note then, that’s 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.