Caregiver Mental Health During COVID; KRAS Resistance: It’s TTHealthWatch!

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.

This week’s topics include mental health during COVID for caregivers, who intended to get vaccinated among younger people, resistance to KRAS, and triglycerides and heart disease.

Program notes:

0:53 COVID vaccine intent in 18- to 39-year-olds

1:52 Lived outside metropolitan areas

2:52 Initiatives to give paid time off

3:29 Caregiver’s mental health and COVID

4:29 Suicidal ideation prominent

5:29 Tailored mental health services needed

6:00 Resistance to cancer drugs

7:00 Hoping for a single mechanism

8:00 Characterizing tumors as they are treated

8:30 Triglycerides and heart disease

9:31 No existing atherosclerosis

10:30 If you treat it can you prevent it?

11:55 End

Transcript:

Elizabeth Tracey: How is COVID affecting mental health among caregivers?

Rick Lange, MD: Resistance to cancer drugs.

Elizabeth: Who is intending to get a COVID vaccine among younger people?

Rick: And are triglycerides associated with atherosclerosis?

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’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange President of Texas Tech University of 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 first to the COVID material for this week because, of course, we’ve passed the official grim milestone relative to deaths and also it looks like we’re going to miss another milestone we were hoping for, which was 70% vaccine coverage by July 4^th. That does not look like that’s going to be the case.

So let’s turn to Morbidity and Mortality Weekly Report, the CDC’s publication. They took a look at COVID-19 vaccination coverage and intent among adults aged 18 to 39 years through May of this year. This, of course, is a cohort that is among those who are not voluntarily going out and getting vaccinated.

They looked at, in the time period from March to May 2021, a survey looking at those folks and what they found was that only 34% reported that they had received a COVID-19 vaccine. Almost 25% reported that they probably or definitely would not get vaccinated. That’s a very daunting statistic of course.

They said, “Well, all right. Let’s look at the factors that are associated with that.” Among that cohort, those with lower incomes, lower educational attainment, those who did not have health insurance, who were Non-Hispanic Black and who lived outside of metropolitan areas had the lowest coverage and the lowest intent to get vaccinated.

Rick: There was a little over 30% that have been vaccinated, but fully 50% said they either were vaccinated or were intending to. That still left another 50%. Half of them said they had no intention of doing it and the other half said they were still unsure.

They probed a little bit deeper, and said, “OK” — as you said they identified the risk factors, but then they asked them the question, “Well, why is that?” It seems like safety and effectiveness were the two major reasons. About 50% were waiting to see if the vaccine was safe and about 40% said that they thought other people needed it more than they did. So if we’re going to reach a 70% vaccination rate across the United States, this is the group we need to target.

Elizabeth: Exactly. The CDC folks do also say that ensuring that vaccines are easily accessible, convenient, and available in places where these young adults live and work could also improve this coverage and acceptance. I think that’s true. There is lots of initiatives underway to give people paid time off and other things so that they can obtain a vaccine.

Rick: But unless they’re convinced that it’s safe, they’re not going to get it. When they asked them what would change your mind, about 39% said, “If I thought it was safe, I would change my mind.” About 30% said that they would do it to prevent spreading COVID to their family and friends. This has been pretty important as well.

These are the messages that we need to get out to these individuals. It’s safe. It is effective. And although you may get COVID and not have severe symptoms, your family or friends could develop severe symptoms and die, and so do it for them.

Elizabeth: Since we’re in MMWR, why don’t we stick with this and let’s talk about mental health among parents of children younger than 18 years old and unpaid caregivers of adults during the pandemic and their mental health. Of course, a big concern.

Early on in the pandemic, almost two-thirds of unpaid caregivers of adults reported adverse mental or behavioral health symptoms, compared with approximately one-third of the folks who were not giving care. In addition to that, almost a third of parents of children younger than 18 years of age reported that their mental health had worsened during the pandemic.

This is a snapshot of how many people are feeling the stress and it’s being manifested as a mental health problem because they are in these care-giving situations? They’re either caring for children younger than 18 years of age in the home, they’re caring for aged relatives, or both.

They surveyed these people and I think the thing that is most startling to me out of this is this issue of suicidal ideation and just how really prominent it was among these people who have been in these caregiving roles.

Rick: The group that we’re talking about is a large group of the US population. Forty percent of the U.S. population is in the role of either parenting a child under the age of 18 or providing care to an adult. I was surprised to learn that 85% of those that have both those responsibilities had worsening of their mental health behavior and 50% had suicide ideation. That’s eight times higher the individuals that had no parenting or adult caregiving responsibility.

This suicide ideation was pretty serious. It was not only “Have I thought about it?” but “I’ve thought about ways that I might engage in it.” This is very alarming.

Elizabeth: It is very alarming, and unfortunately this potential solution is multifactorial and it’s not going to be easy to implement.

Rick: It’s not, but we need to recognize that it’s not just the individuals that have COVID that are affected. Everybody may be affected in one way or another. Recognizing it’s a major need and meeting that need is critical.

Elizabeth: They recommend tailored mental health services. To me, that suggests even more of a barrier. Because if we need to assess this on an individual level and then tailor it to the individual, we have a lot of individuals to try to intervene.

Rick: Right.

Elizabeth: One of the durable lessons of COVID is that we really need to get our arms around providing mental health care services because this need for caregivers is projected to increase as the U.S. population continues to age.

Rick: Yup.

Elizabeth: Which of your two would you like to turn to first?

Rick: Let’s talk about resistance to cancer drugs. We have spent a fair number of podcasts over the last two decades talking about individualized therapy. There was a time where we looked at cancer as being a part of an organ. You’ve got a specific treatment if you have liver cancer, or lung cancer, or colon cancer.

Now we’re realizing each of these cancers has specific pathways that cross different organs and so what we’re trying to do is hone in on those particular pathways to provide individualized cancer therapy.

One of those is directed to what’s called KRAS. It’s one of those commonly mutated alkA genes in cancer. This KRAS functions as a switch. It’s in the “off” or “on” form. When it’s in the “on” form, what it does is it promotes tumorigenesis, or tissue developing into tumors. We have developed specific therapies designed against this KRAS and they have been successful. Unfortunately, individuals can develop a resistance.

What these authors attempted to do was to define how that occurs. They looked at 38 individuals — 27 had lung cancer, 10 had colorectal cancer, and one had appendiceal cancer — and then looked at the different mechanisms, hoping that you’ll find a single mechanism and we could attack that.

Well, unfortunately, what they found is it’s not a single mechanism. In some, it’s an alteration in the KRAS gene. In some, it’s not KRAS, but it’s the other pathways underneath it that are influenced. And in some individuals, the tumor actually changed. These investigators give us an insight on how difficult it is to address these particular issues.

Elizabeth: Right. Let us just note that this is in the New England Journal of Medicine. One of the issues, I think, that this brings up is that we probably are going to need sequential genomic analysis of people’s tumors as they live, and if their cancer recurs, because a recurring cancer is not the cancer you started with and this is really going to pinpoint the need for that genetic analysis virtually continuously.

Rick: Absolutely. What happens when you start treating a cancer is there are very strong selective pressures. There is a convergence of these different resistance mechanisms. For example, some of these individuals, about 40%, didn’t have a single resistance mechanism, they had several different ones. You’re right. Categorizing the tumor as we treat it, providing sequential therapy or combination therapies based upon that as well.

Again, treating cancer isn’t as simple as it seems — a single cancer, a single drug, a single cure. It’s going to take continued, as you said, genetic analysis. You think you get it right at the headwater and all of these little tributaries will pick — uh uh. That’s not the case. These little tributaries end up circling back around and still driving tumor growth as well, so more to learn.

Elizabeth: Absolutely. Now, let’s turn to the journal of the American College of Cardiology, this ongoing issue we were talking before we recorded about how we seem to talk about so many different topics again and again as more information is uncovered, and we’ve quipped, of course, “Should we put statins in the water?” Now, this look at even if you do that, maybe you’re not going to be able to ameliorate a lot of the cardiovascular disease.

Rick: Everybody is familiar with the fact that cholesterol is associated with atherosclerosis or hardening of the arteries that affects the brain and affects the arteries in the heart, and arteries throughout the body and the limbs as well. That’s associated with cholesterol and particularly low-density lipoprotein cholesterol.

There has been a lot of controversy about whether triglycerides, in and of themselves, were independently associated with atherosclerosis, and because they are associated with these other cholesterols, trying to tease that out hasn’t been particularly easy.

But what these authors did was they took a unique approach. They took over 3,700 middle-aged individuals that had low to moderate risk of having atherosclerosis — that is they had a normal or low LDL cholesterol, so they weren’t at risk for atherosclerosis, they didn’t have any atherosclerosis, but then they examined their subsequent risk of developing it, by looking at three different measures.

One is, they did a sono of eight different arterial systems in the body. Number two, they looked at coronary artery calcifications so they could look at progression in the heart. The third thing they measured was inflammation.

What they discovered is even the individuals who had low or normal cholesterol levels, particularly LDL cholesterol, the triglyceride level was associated with the development of subclinical — that is, they didn’t have symptoms — atherosclerosis in the arterial system and a two-fold increased risk of inflammation.

Now interestingly enough, it wasn’t more calcium in the heart, but oftentimes that’s a later phase. That is, you develop inflammation first, develop some deposition of atherosclerosis, and then develop calcification late, so that’s not terribly surprising. I think this is another piece of the puzzle that suggests that triglyceride levels are in fact associated with atherosclerosis, even in individuals who have normal cholesterol.

Now, the next question is, if you treat it, can you prevent it? And that we don’t know the answer to. You say, well, of course, this makes sense. Sometimes things makes sense, but they just don’t particularly work out. For example, we know that high HDL levels are associated with decreased atherosclerosis, atrial cholesterol. But when we raise those levels, it didn’t actually help at all. Even though we have made an association between triglycerides and atherosclerosis, we can’t take the next step yet and say that treating the triglycerides alone is going to lower your cardiovascular risk or risk of stroke.

Elizabeth: Yeah. This is so disappointing, isn’t it? It sounds an awful lot like the KRAS pathway, where we really thought we had identified something that was the smoking gun and it turns out that it’s not the whole story.

Rick: Well, there are oftentimes pieces to the story and the reason why this is important is, we have people with low or normal LDL cholesterol who still develop atherosclerosis. You say, “But what is that about and is there something we can do to prevent that?”

Now, we know what that something else may be — it’s triglycerides. The next step is to say let’s take these same individuals, low to moderate risk, and lower their triglycerides over a long period of time and see if we can prevent future atherosclerotic events like stroke or heart attacks. I’m sure that will be coming down the road.

Elizabeth: Yes. 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.