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 treating intracerebral hemorrhage, diagnosing forearm fractures in kids, ketamine and electroconvulsive therapy (ECT) for depression, and defining post-acute sequelae of SARS-CoV-2 infection (PASC).
Program notes:
0:38 Defining PASC
1:38 Loss of or change in smell
2:38 Common physiologic features?
3:38 Look at ways of treating it
3:53 Treatment-resistant major depression
4:51 Only 41% in ECT group
5:51 Not cost effective in clinics
6:55 Treating intracerebral hemorrhage
7:55 Rapid reversal of warfarin
8:55 Even in high-income counties
9:25 Diagnosing distal forearm fractures in kids
10:25 Ultrasound increasingly adopted
11:25 Results just as good as radiography
12:30 End
Transcript:
Elizabeth: What’s the best way to treat a bleed in the brain?
Rick: Ketamine versus electroconvulsive therapy for treatment-resistant depression?
Elizabeth: Can we define post-COVID sequelae?
Rick: Using ultrasound to diagnose suspected arm fractures.
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: In keeping with our habit for the last 3 years, we’re going to turn straight to JAMA and we’re going to take a look at post-acute sequelae of SARS-CoV-2 infection known in all caps as PASC and colloquially called “long COVID.” This is a study that had 85 enrolling sites in 33 U.S. states plus Washington, D.C. and Puerto Rico. They had a total of 9,764 participants, 89% of whom were infected with SARS-CoV-2, 71% female, and their median age of 47 years.
They are trying to define what does PASC look like. Their symptoms that contributed to their PASC score calculation included, and I’m going to name them all, post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements.
Among their 2,231 participants first infected on or after December 1, 2021 and enrolled within 30 days of infection, they found that there were 10% of them who were PASC positive at 6 months. There is a number of other kind of slice and dice attempts among this population to further define it.
Rick: The reason they chose this particular timeframe is because, as they noted, you are more likely to have long COVID symptoms if you were unvaccinated, if you happened to be re-infected, and if you had received the Omicron variant as opposed to infection with another variant. The reason why to get our definitions around this is we’re trying to do a couple things. We’re trying to identify how commonly this occurs. We’re trying to see if there’s some common physiologic reasons about why these occur. If we do that, we can talk either about treatment or long-term outcomes.
Elizabeth: I get it. I would also say that the editorialist points out a number of really curious facts — that nearly 4% of people without a history of COVID-19 met the score cutoff for PASC. And then the substantial overlap between folks who have the constellation of symptoms that defines myalgic encephalomyelitis or chronic fatigue syndrome and what happens in this PASC definition also. Finally, that so many of these folks are female.
Rick: There may be some overlap because there may be a common root cause among all these things. For example, in the study that you mentioned, not only do they collect the clinical data, but they actually bank bile samples as well. Maybe by looking at this with this condition, or other viral illnesses — for example, those that cause chronic fatigue syndrome — we can find some commonalities that allow us to either predict what will occur or look at ways of treating it or assessing the natural history.
Elizabeth: I think we got a lot more work to do. I agree with the editorialist. It’s an important initial framework for this work to go forward. Which of yours would you like to turn to, sir, both in NEJM [New England Journal of Medicine]?
Rick: Let’s talk first about treatment-resistant major depression. Electroconvulsive therapy has long been used for over 80 years now for this particular condition. More recently, using sub-anesthetic intravenous ketamine has also proven to be effective for people that have treatment-resistant major depression. We’re talking about people that have an unsatisfactory response to two or more adequate trials of antidepressants, which is about a third of the 21 million adults in the United States that have major depression.
What these authors did was they compared the two. It’s a randomized non-inferiority trial of 403 patients at five clinical sites randomized to receive either ECT or ketamine. They follow these patients after the initial treatment phase and those that had a positive response additional over a 6-month period. What they discovered was that with regard to initial response, a total of 55% of the patients in the ketamine group and only 41% of those in this ECT group had a response. Ketamine was actually non-inferior.
When they look over a longer period of time, the results were similar. Those that had ECT were more likely to have some problems with memory early on. Those that received ketamine were more likely to have dissociative thinking. It suggests that ketamine can be used rather than ECT in this particular group.
By the way, this particular group did not have psychosis. We know that ECT is particularly helpful in older individuals and those that have treatment-resistant depression and psychosis. Those people were excluded from this particular study. ECT is oftentimes not administered. There is a stigma attached to it, so to be able to use sub-anesthetic doses of ketamine for this patient population and having an outcome that’s just as good or a little bit better is very encouraging.
Elizabeth: It’s also really interesting. As you’re well aware, ketamine clinics that have popped up all over the place are now closing in record numbers because people can’t make the numbers work. It’s not cost effective for those who have been operating them to actually continue to do so. My question about this application for ketamine is how many episodes or how many administrations of ketamine were there in comparison to how many times ECT was used and were these under what conditions.
Rick: During the initial 3-week treatment phase, patients received either ECT three times per week or ketamine twice per week.
Elizabeth: In my witness to this, it seems like the ketamine is easier to administer than the ECT. Is there any reflection about that in this paper?
Rick: This was done in the outpatient setting. ECT previously wasn’t used that way, but it’s actually been refined and safe in that setting as well. Giving sub-anesthetic doses of ketamine can be done in the outpatient setting as well. With regard to the cost-effectiveness, this study did not address that at all.
Elizabeth: Well, I think there is going to be ongoing debate about this just as … we debate many things. Over the long haul, I think there is going to continue to be some controversy surrounding this.
Let’s turn now to The Lancet and this is a study that they say is primarily, at least in this study, targeted to low- and middle-income countries. However, the authors prognosticate that they think their findings could be very useful for higher-income countries also. They are looking at hemorrhagic stroke and their central hypothesis is that early control of elevated blood pressure is the most promising treatment for acute intracerebral hemorrhage.
They enrolled patients from nine low-income and middle-income countries and one high-income country, Chile. They had imaging-confirmed spontaneous intracerebral hemorrhage and the patients presented within 6 hours of the onset of symptoms. They used a bundle of interventions to try to improve outcomes here. The bundle included intensive early lowering of systolic blood pressure, strict glucose control, anti-fever treatments, and rapid reversal of warfarin-related anticoagulation. Their primary outcome measure was functional recovery.
They had over 7,000 patients enrolled. Just shy of 3,000 of them were in the care bundle. What they showed was that the patients in the care bundle group had fewer serious adverse events and they had better outcomes than the folks who weren’t.
Rick: This is relevant because worldwide intracerebral hemorrhage accounts for about 20% of the almost 20 million new strokes that occur each year. As you said, this is a study where they threw the kitchen sink out. They said let’s do everything we can think of that could possibly help them lower their blood pressure, lower their sugar, treat their fever, and reverse their anticoagulation. They did have a better outcome. However, when they went down and looked at which had the most significant effect, it seemed to be lowering blood pressure, lowering the systolic blood pressure to less than 140.
Elizabeth: As I said, the authors prognosticate that, gosh, even here in high-income countries, we don’t have a lot of really wonderful things to do for folks who have intracerebral hemorrhage and that it will be well worth employing this strategy globally.
Rick: In fact, globally, the most common cause of intracerebral hemorrhage is elevated, untreated, uncontrolled hypertension. Therefore, it should be no surprise that in these primarily low- and middle-income countries, lowering the blood pressure in them could significantly improve the outcome with intracerebral hemorrhage.
Elizabeth: OK. Back to NEJM. Diagnosing distal forearm fractures in kids.
Rick: This is an interesting study. I never thought about using an ultrasound to diagnose fractures, but these, what are called distal forearm injuries, in children and adolescents really a frequent reason why they go to the emergency room not only in the United States, but worldwide.
The most common fractures in children are what’s called buckle fractures, that is, there is not a clear break. It just buckles and it’s akin to almost a soft tissue injury. You don’t have to really put a cast on it. You can treat it with a splint or even a bandage. Typically that’s diagnosed by radiography. If the kid has a clear deformity, they have a fracture. But the buckle fractures are really hard to see on the surface, so typically an x-ray is done.
Unfortunately, approximately two-thirds of the world actually lacks access to diagnostic imaging. I wasn’t aware of that, Elizabeth, but we just kind of take it for granted. But ultrasound has been increasingly adopted in these low- and middle-income countries because it’s portable and it’s very affordable.
What these investigators did was they compared using ultrasonography or radiography for suspected pediatric distal forearm fractures. This was conducted in Australia. They recruited patients who were 5 to 15 years of age. They presented to the emergency department with a forearm injury without clinically visible deformity and they would normally be referred to imaging. Half the kids were referred to radiography, the other half were referred to ultrasonography, and then they followed the outcome at the end of 4 weeks to see what the physical function was in the arm.
What they discovered was that the scores at 4 weeks in those that had ultrasound were exactly the same as those that had radiography. Those scores being the functional assessment of the kids.
If someone had ultrasonography and it looked like there was an honest-to-good enough fracture, then they went on to receive radiography — that was about 25% of the kids — and then they went on to get a cast. This shows that in adolescents and kids with a distal forearm injury, ultrasound can be used as the initial diagnostic method and the results can be just as good as routine radiography.
Elizabeth: I think this is really good news. We’re both familiar, of course, with just the explosive growth of point-of-care ultrasound. It seems like everybody’s got that. We’re also familiar with the fact that we’re trying to reduce exposures to radiation and so it sounds like a win-win here.
Rick: Yep, it is Elizabeth. Not only that, but it takes a radiologist actually to read an x-ray. But they actually had a diverse group of healthcare practitioners who were trained in how to read the ultrasound. Physicians, nurse practitioners, and even physiotherapists read the ultrasounds in this particular group. I think this is really interesting. I wasn’t even aware we were doing ultrasounds to make this diagnosis. I’m glad you picked this study.
Elizabeth: Excellent. 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.
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