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Delirium and Dementia; Are Biosimilars Cheaper for Patients?

— Also in TTHealthWatch: preventing infections by drug-resistant bacteria

MedpageToday

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 decolonizing patients and infections in the hospital, delirium and dementia, brain size over the last few decades, and whether biosimilars are cheaper for patients.

Program notes:

0:35 Brain size over the last few decades

1:35 About a 7% greater volume

2:35 Bigger brains start in early childhood

3:55 Biosimilar costs

4:53 Cost about 10% higher

5:45 Does delirium predict dementia?

6:46 Recurrent delirium with dose response

7:47 Programs to reduce delirium in older patients

8:51 Multidrug-resistant organisms, iodine, and chlorhexidine

9:52 Decolonize every 5 days

11:04 Don't need surveillance

12:27 End

Transcript:

Elizabeth: Does delirium predict dementia?

Rick: Preventing infections by drug-resistant bacteria.

Elizabeth: What's happened to the size of our brains over the last few decades?

Rick: And are biosimilar drugs really cheaper for patients?

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: 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, with your permission, I'd actually like to start with JAMA Neurology. The reason I want to start with this is I said what has happened to the size of our brains over the last several decades. This is of great interest to me. I used to teach anatomy and physiology, and I've dissected many cadavers that I find a lot of these things to just be so intellectually curious. That's what attracted me to this particular study.

It's taking a look at intracranial and cerebral volumes in folks who participated in the Framingham Heart Study born between 1930 and 1970. These people did not have dementia or a history of stroke and had MRIs that were obtained between 1999 and 2019. This is a cross-sectional analysis of intracranial, cortical gray matter, white matter, and hippocampal volumes, and cortical surface area and cortical thickness.

The cohort was 3,226 participants, about half and half male and female. Sure enough, when we compare those from the '30s to those in the '70s, we find that there is just shy of a 7% greater volume. There is also greater white matter and hippocampal volume. The authors say, well, can we tie together improved brain development, which is what they call this, and what we're noticing as declining dementia rates in that Framingham cohort?

Rick: They mentioned declining dementia rates, but it looks like we're seeing more and more people with Alzheimer's now than we did before, but that's because we're living longer. The incidence of dementia, particularly in this Framingham group -- and remember this is a group that was originally put together to study heart disease, but as you mentioned they have MRIs for people ranging in birth from 1925 to 1968. What they are saying is bigger brains, better brain health because IQs have gone up over the same period.

However, they also note that the height has gotten taller and that ties in with how big brains are. There may not be a relationship between bigger brains and better brain health. They allege, however, that bigger brains starts in early childhood and we're healthier, and there may be some truth to that. We have better nutrition and less infectious disease, but it doesn't prove a cause. But it's nice to say "bigger brains, better brains" -- it just sounds good.

Elizabeth: They do note, the authors, that this is a very prescribed cohort and that these are not results that would necessarily be seen if we examined other cohorts over the same amount of time. A couple of other things I thought were really interesting is that cortical thickness is actually less. The question is, is that sort of spreading it out over all those neurons and the gray matter?

Then they have this thing that they call gyrification. All of us know that there is kind of these hills and valleys that decorate the surface of the brain and then allow it to have this greater surface area in terms of the cerebral cortex. I just think it's really fascinating. It's one of those things like, wow, are we ever going to lose our appendix? Our brains are getting bigger. It's just quite interesting to look at.

Rick: Elizabeth, for those listeners who have been following us for almost 20 years now, they are not going to be surprised that you find the most unusual things fascinating and bring it to our attention, so thank you.

Elizabeth: Thank you. Which of your two would you like to start with?

Rick: Elizabeth, I'm going to pick one from JAMA Health Forum. I think this may be the first time we've reported for JAMA Health Forum. Are biosimilars cheaper for patients? Biologic drugs that have come on the market that are similar to the original ones. When the original biologic drugs come out ... and they treat a number of different things. They're primarily antibodies, though, and they're always expensive. As the patent wears out, we're able to develop biosimilar drugs and the thought would be is that these biosimilar drugs, because there is now competition, is the price will go down and be cheaper primarily to patients.

They looked at 7 different biologic drugs and their biosimilar drugs between 2009 and 2022. They looked at over 1.7 million insurance claims from over 190,000 different individuals. What they were most interested in is the out-of-pocket cost. The annual out-of-pocket cost actually increased before and after biosimilar availability; 2 years after the biosimilar drugs were available, the out-of-pocket costs were actually about 10% higher.

Elizabeth: Is this a question of regulation? I mean, what's going on here? That doesn't make any sense to me.

Rick: Well, Elizabeth, in fact that's exactly what the investigators alleged. Listen, having biosimilar drugs available where there is competition across the entire healthcare system saves billions of dollars. To the individuals paying for it, that doesn't really matter. I say it doesn't matter. It does lower insurance premiums, so that's a benefit, but you'd like for it to benefit the individual as well and that's probably going to take some regulation.

Elizabeth: I find this whole thing -- and this is just one little snapshot -- to just be so complex and very difficult to discern where exactly are these cost savings going when there are biosimilars developed.

Rick: Yeah. The company still wants to make a profit, so there's a little bit of savings, but we need to pass it on to the patient. It looks like that's going to take some regulation or legislation to do that.

Elizabeth: Let's turn to the BMJ. This is a look at something that I see pretty often in the medical intensive care unit, MICU, and that's delirium. This is a study from Australia that takes a look at if you have delirium, does that predict that you are at risk to develop dementia?

They looked at data from 650,000+ hospitalized patients who were older than 65 years of age. Those who had dementia at baseline were excluded. They had delirium no-delirium pairs identified by matching personal and clinical characteristics, and they followed these folks for more than 5 years. They ended up having 55,000+ matched pairs.

What they showed was that 17% had a newly reported dementia diagnosis. During that 5.25 years of follow-up, those with delirium had almost a 40% higher risk of death. They also had a three times higher risk of incident dementia after they had had this episode of delirium interestingly, and the numbers start to break down a little bit here when they extend this.

They also showed that for those who have recurrent occurrences of delirium while they are hospitalized, there is kind of a dose response relative to the development of dementia on the far side of that. I thought their biological explanation was a little bit stretched.

Rick: For those listeners who may not have seen delirium, it's some acute event in the hospital, it's an illness or a surgery, that leads to the patient having some change in their baseline cognitive function so that they are inattentive or there is some disturbance of their awareness. It's self-limited and people get over it.

This isn't the first time there has been a relationship associated between those two. Is their baseline cognitive dysfunction and the delirium unveils oncoming dementia? Or is there something that delirium does biologically that increases the risk of dementia in otherwise normal people? Which is it?

Elizabeth: That's, of course, the bazillion-dollar question and the one that everybody would like to develop an answer for. That sort of brings us all the way back to their conclusions relative to this because nobody really knows that. However, they do talk about programs that have been undertaken in Australia that appear to help reduce the incidence of delirium for older hospitalized patients.

They have something that's called the Hospital Elder Life Program, HELP, that reduces this incidence of delirium while folks are in the hospital. Does it ultimately reduce subsequent dementia? I don't know if they have enough data to really be able to answer that question.

Rick: But clearly delirium is a marker, if not a cause, for subsequent dementia.

Elizabeth: I would just also note that this Hospital Elder Life Program and other strategies to try to reduce delirium while someone is hospitalized, I think, are incredibly worthy. Because delirium can persist for a very long time, surprisingly a long time, and it's extremely distressing to the loved ones of patients.

Rick: Right. I mentioned that it's transient. I didn't mean to imply that it's pretty short. It does go away eventually and that's one of the definitions of delirium. The next step is does preventing delirium prevent subsequent dementia. We need to prove that.

Elizabeth: Finally, turning back to JAMA, can we do something about these multidrug-resistant organisms in hospitals and nursing homes?

Rick: These are bacteria that are oftentimes resistant to our typical antibiotics, and this become a big problem primarily in hospitals where as many as 15% of hospital patients may be colonized with these, but more importantly, as many as 40% to 65% of nursing home residents and 80% of individuals in long-term acute care hospitals may have colonization with these drug-resistant organisms.

Because individuals bounce back and forth between nursing homes and hospitals or hospitals to long-term care facilities, you can see how these can spread.

What the investigators of this particular study hypothesized is if we're going to address this, we need to address it in the network. They identified 35 healthcare facilities in Orange County, California, and decided to try to decolonize. What that means is they tried to put iodine solutions in the nose for 5 days every other week and also to use routine bathing with chlorhexidine-containing products. Did it in fact decrease both colonization and subsequently hospitalization with these drug-resistant organisms?

There was in fact between a 15% and 35% decrease in the prevalence of colonization across all these facilities, and more importantly about a 27% decreased incidence of hospitalization with these drug-resistant organisms, and the cost savings as well. This is a really robust study. In fact, this is so robust that when the results became available the state of California decided to do this in other facilities as well.

Elizabeth: We certainly are in dire need of things that are going to intervene in this transmission of multidrug-resistant organisms in these facilities, hospitals and long-term care facilities. To me, this sounds like a win-win.

Rick: It is. It's cost effective. We're not using antibiotics that actually increase resistance. It's simple. It's easy to train individuals to do this and it doesn't require routine surveillance. You apply it to everybody because it's so easy to do and you get significant results.

Now, the key to this, Elizabeth, was to identify networks -- where do these long-term health facilities and nursing homes admit their patients -- and make sure that you target those hospitals.

Elizabeth: I guess one other thing that we are definitely going to need to watch is what is the long-term consequence of applying these two particular agents to people's skin and to their intranasal passages. There was some data that emerged during COVID about the downsides of iodine-based washes for the nasal passages, so I'm wondering about that.

I'm also wondering about is that as people age, we know their skin becomes a good deal more sensitive to things and fragile. That's another question that I would wonder about over the long haul. Finally, I would say over the long haul, will this select for organisms that will be ultimately resistant to chlorhexidine and iodine?

Rick: Elizabeth, those are all valid points. In fact, the authors of the study listed those as limitations of this study and I suspect now that they have done this we'll be able to collect that data.

Elizabeth: Okay. On that note then, that's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.

Rick: I'm Rick Lange. Y'all listen up and make healthy choices.