Consequences of Afib; Autism Heritability in Males and Females

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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 autism rates among males and females, consequences of atrial fibrillation, antipsychotics among those with dementia, and antibiotic use utilizing artificial intelligence.

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Program notes:

0:41 Atrial fibrillation and its complications

1:41 Increased risk factors

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2:41 Treat with medication or ablation

3:30 Autism heritability in males and females

4:30 No support for environmental shared factors

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5:33 Tried to account for with modeling

6:23 Antibiotics, artificial intelligence, and common infections

7:23 50 different variables

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8:23 Patient-specific factors

9:10 Antipsychotics and dementia

10:10 New antipsychotic use increased risk of pneumonia

11:10 Care providers

12:42 End

Transcript:

Elizabeth: Can we explain the different rates of autism between males and females?

Rick: The lifetime risk of atrial fibrillation and its complications.

Elizabeth: What are the adverse outcomes associated with any psychotic use in people with dementia?

Rick: And harnessing our electronic health records to improve our antibiotic prescribing.

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, if you’re okay with it, I would like to start with The BMJ and this issue of atrial fibrillation and its complications, which this study was kind of a surprise to me.

Rick: I tee this up as the lifetime risk of atrial fibrillation, and they used the Danish nationwide population information to look at how common is atrial fibrillation over a lifetime and specifically what complications are associated with it.

They looked at two different decades, 2000 to 2010 and then 2011 to 2020, to compare those two different decades. Atrial fibrillation is an irregular heart rhythm, where the upper chamber of the heart kind of quivers. In the U.S. alone in the next 20 to 25 years, there will be about 16 million people that have it.

What’s the danger? They said, okay, let’s say you make it to age 45 and you haven’t had atrial fibrillation. What’s the risk that you’ll get it before you turn 100? Once you have it, what are the associated complications? In the first decade between 2000 and 2010, it was about 1 in 4 individuals over the age of 45 developed atrial fibrillation. In the most recent decade, it’s now 1 in 3. That may be because we have had increased risk factors like high blood pressure, obesity, and diabetes, and it is more common in men as well.

Here was a surprising thing to me. All healthcare providers and most of our listeners will be aware that it’s associated with an increased risk of stroke. About 20% of the individuals experienced a stroke after atrial fibrillation, despite the fact they were supposed to be on blood thinners. But the amazing thing is they were twice as likely, there were 40% of those, that actually developed heart failure. Then about 15% developed a heart attack.

Unfortunately, even though we have gotten better at diagnosing and trying to treat atrial fibrillation, the incidence of those was a relatively minor decrease. Atrial fibrillation is on the rise and the complications happen pretty frequently.

Elizabeth: I thought it was just surprising, this rate of heart failure, and I think they were a little bit surprised by that also.

Rick: Yeah, 40%. If you’ve got a 1-in-3 risk of developing atrial fibrillation and 40% of those develop heart failure, that says something. About a third of patients really don’t have symptoms. When they do have atrial fibrillation, it is to treat either with medications or we now have ablation to hopefully help lower that risk. But more importantly is to prevent it from occurring.

The risk factors for heart failure are the same for atrial fibrillation. We can reduce the risk of atrial fibrillation and its complications if we control those things.

Elizabeth: Allow me to also interject a question about exercise and its ability to prophylax against development of atrial fibrillation.

Rick: It’s a really interesting thing, Elizabeth. If you’re an elite athlete, it actually increases your risk of atrial fibrillation. But for those of us that do a modest amount of exercise, 150 minutes a week, it actually lowers all the other risk factors and also reduces the risk of atrial fibrillation as well. If you’re serious about preventing heart failure and you’re serious about preventing atrial fibrillation, a lot of that is within our control.

Elizabeth: That’s the good news. Let’s turn, since we’re over in this area of the world, to Sweden. This is JAMA Psychiatry, the study that was examining sex differences in autism heritability. Autism spectrum disorder [ASD] is extremely common and it feels like it’s getting diagnosed more and more often. Nobody has ever really tried to nail this down in this particular way before.

The authors put forward the fact that the cause of ASD is largely genetic and they wanted to look at the sex-specific heritability of this disorder. Using the health registers of non-twin siblings and cousins from Sweden between 1985 and 1998, they followed them up to 19 years of age. They had a sample of over a million individuals, with each family having about two children; 1.17% of that sample received a diagnosis of ASD — almost twice as many males as females.

They estimate the heritability among the males at 87%, and at 76% for females. It said there was no support for shared environmental contributions. They posit a number of potential reasons that might be true, but they don’t really come to a conclusion.

Rick: Part of that, Elizabeth, is that even though 2% to 3% of American kids will be diagnosed with an autism spectrum disorder and we know there is some heritability, there are probably some environmental or other things that we just don’t understand.

Let me take a step back for a second, because some kids with ASD have intellectual disability and some don’t. It appears that those with intellectual disability and autism that the heritability between males and females is the same. But it’s those that have the less severe form where it looks like the males have an increased heritability than the females.

Now, maybe they are more likely to develop it. It could be something about the females that’s protective. Some of it is the age at which they are diagnosed — because females are typically diagnosed later than males — and the presentations are different. They tried to account for all of this by doing different modeling. I would agree with you that there is an increased incidence among males. Exactly why that is, is still unknown.

Elizabeth: They talk about this female protective effect, which we have seen in other circumstances that female sex just seems to confer protection. We even know this if we examine lifespans, for example. They tried to correct for so many of these factors, though — the usual suspects like parental age, the existence of the condition already in the family. Again, I feel like they are saying, “Yep, okay, there are a number of possibilities, and the answer is we don’t know.”

Rick: Yeah, I mean, for almost 20 years we have been reporting, we very seldom reported on ASD initially and now it seems like we’re reporting on two or three things per year. We’re trying to get to the root cause.

Elizabeth: Indeed. Okay, so let’s turn to JAMA. What are we going to do about these antibiotics? How can we use them best in common infections?

Rick: Another surprising fact is that approximately half the hospitalized adults in the U.S. receive antibiotics. The two most common infections, by the way, are pneumonia and urinary tract infection [UTI]. Again, over the last two decades, we have talked a lot about antibiotic stewardship, making sure the person has a bacterial infection, they’re on the right antibiotic for their particular organism, and we keep them on it for the minimal amount of time. We’re doing this to try to prevent resistant bacteria, what are called multidrug-resistant organisms or MDROs.

The way we typically do that is we admit somebody and we put them on a broad spectrum. We do that because we don’t know what the organism is and we’re concerned it could be a really deadly one. Get cultures to find out what bacteria is infecting them and then 3 or 4 days later we change the antibiotics.

But what these investigators said is, hey, wait a minute. Less than 10% of individuals have a multidrug-resistant organism infection. Can we target those individuals for the broad spectrum and for the rest of them use something that’s less selective?

To do that, they actually used the electronic health record [EHR] and they looked at 50 different variables. Some of them are related to the organism. Some of it related to the patient, their comorbidities, and where they have been hospitalized. It predicted whether or not they were going to have an infection with a multidrug-resistant organism and needed broad-spectrum antibiotics or they didn’t.

They reduced the broad-spectrum antibiotic use in those with pneumonia by about 30%. For those with urinary tract infection, it reduced it by about 20%.

Did it harm the patients that were in the hospital longer? Do they have to go to the intensive care unit? Did they have to switch antibiotics? The answer is none of those things. These were patients that were hospitalized with pneumonia or a UTI, but weren’t going to the intensive care unit, so it looks like the electronic health record can improve our antibiotic stewardship. This is really a good news story.

Elizabeth: It’s a great news story, and I guess I’m interested in what some of those factors are that predict what specific organism someone might be infected with.

Rick: They look at what I call a local antibiogram. What are the most common organisms causing pneumonia or urinary tract infection in that particular hospital region and do they respond to antibiotics? Then there are patient-specific things like demographics and comorbidities. Do they have a prior healthcare exposure, which would increase our risk overall?

Elizabeth: Well, I’m really interested in this notion that there are local flora, that there are certain organisms that are found in certain regions and that are most commonly going to cause infections. What I would love to see would be a study over time, or seasonally, that looks at variations among that population and I’m sure we can get that data.

Rick: Yep. In fact, what you mentioned is one of the limitations of this study. First of all, it requires a large EHR, and some small hospitals don’t have that or local doctors don’t. The second is people have moved from region to region. If we’re going to really, broadly apply this, we’re going to have to look at how to overcome those things.

Elizabeth: Finally, let’s turn back to The BMJ and this is a situation that we also have reported on previously: adverse outcomes associated with antipsychotic use in people with dementia.

This is, however, a really big study from the Clinical Practice Research Datalink, CPRD, in England. They had adults 50 years of age or older with a diagnosis of dementia between 1998 and 2018 — just shy of 200,000. Each new antipsychotic user, which was 35,000+, was matched with up to 15 non-users using this incidence density sampling.

What they wanted to find out was if you are on an antipsychotic, did you experience stroke, VTE [venous thromboembolism], an MI [myocardial infarction], heart failure, ventricular arrhythmia, fracture, pneumonia or acute kidney injury. Then they had as negative controls the outcomes of appendicitis and cholecystitis.

Sure enough, if you were on a new antipsychotic, you did have an increased rate of primarily pneumonia. That was the biggest increased risk. But all these other risks were also increased with that. They did not observe any increased risk in appendicitis or cholecystitis. It was pretty concerning and confirmatory of what we have reported on previously.

Rick: Unfortunately, the use of antipsychotics in people with dementia was starting to decline, and then during the COVID years it actually increased. We have known for, gosh, about 15 years that the antipsychotics are associated with the complications that you mentioned, and they really have very marginal benefit at all.

We need to be really restrictive in who we give these medications to — for those that prescribe medications, to be aware of this, but also for caregivers as well. Because we think the easiest thing to do is if mom or dad has dementia and we can try to control the antipsychotics, we can actually increase the risk of these severe complications and shorten their life.

Elizabeth: I guess my heart really goes out to care providers for people with dementia and the huge struggle it can be to deal with a lot of these behavioral issues. The temptation to turn to … and I should mention in this study that they note that risks are associated both with what are called atypical antipsychotics as well as typical antipsychotic drugs. It just seems like, gosh, this is a fix for something that can be quite intractable.

Rick: It is. One of the things that the investigators mentioned is that we actually need to do more research into what are some safer drug treatments. If there are behavioral or environmental changes that we can make short of using medications, that would be the actually preferred treatment.

Elizabeth: They note that the attempt to use other things hasn’t been very fruitful either with what we have currently in the armamentarium. Let’s just then end with the authors’ perception. They state that when an antipsychotic prescription is the least bad option clinicians should try to do it for the shortest period of time as possible.

Rick: Both the smallest dose, it gets the desired effect, and for as short as possible. Great.

Elizabeth: On that note, 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.



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