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 when to clamp the umbilical cord in premature infants, vitamin C for people hospitalized with COVID, visualizing cardiac stents after placement, and early childhood interventions for autism spectrum disorders.
0:37 Making coronary stenting safer
1:37 Intravascular Imaging after stenting improved outcomes
2:31 Autism interventions
3:31 Shared control between the child and the person conducting the intervention
4:31 Not much evidence that’s reliable
5:31 Very early intensive intervention
7:01 No help in either of two groups
8:00 Clamping the umbilical cord in premature infants
9:00 Already saw a benefit with delaying in full term infants
10:05 May stabilize neonatal circulation
Elizabeth: When should the cord be clamped in premature infants?
Rick: Do patients hospitalized with COVID-19 benefit from intravenous vitamin C?
Elizabeth: What do we know about interventions for autism early in childhood?
Rick: And making coronary stenting more effective.
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: And 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, I’m going to turn right to you. Which one would you like to start with?
Rick: Let’s start with the one I have teed up as making coronary stenting safer.
Elizabeth: In The BMJ.
Rick: Thank you, Elizabeth. For people that have coronary artery disease and have symptoms that’s refractory to medication, or have very complex disease, they either have bypass surgery or they have stenting performed. Typically, when we do the stenting, we take a picture of the arteries — called coronary angiography — we put a stent in and we take more pictures. There is an alternative to that. After you take your pictures and put the stent in, you can actually look at the stent from inside the artery. That’s called intravascular imaging. Does doing that extra imaging afterwards benefit the patient?
These investigators did a systematic review and a meta-analysis of all randomized controlled trials comparing the results after intravascular imaging versus routine coronary angiography in about 12,000 patients. What they discovered was, those that had the imaging done after the stent was placed had a lower risk of cardiac death by about 47%, subsequent heart attack by about 19%, less likelihood that the stent would clot or have thrombosis by about 56%, and about 26% less likelihood that that vessel would need to be re-vascularized.
Elizabeth: It sure sounds like that’s a slam-dunk to me. What are the downsides to the intravascular imaging?
Rick: It prolongs the procedure. It prolongs the amount of radiation that the patient is exposed to. It also increases the amount of contrast agent — people that have kidney damage, that can make the kidney damage worse. It also cost a lot more.
So when the authors looked at this, they said, “OK, it looks like it benefits patients, but which group benefits the most?” Those that have disease of the left main — the major artery — or those that have complex disease seem to benefit the most. It tells whether the stent is properly placed, is it properly inflated, do we need to do additional work, or should we just leave it as it is?
Elizabeth: Since we’re in The BMJ, let’s stay there, an interesting study looking at autism interventions. This is also a systematic review and meta-analysis of early childhood studies that’s known as Project AIM. These folks did this exact same thing just a few years ago, but since then they have had a bunch of other research that’s actually turned up, so they thought, “All right, we need to do this again.”
They found 252 studies representing over 13,000 individuals and effects for almost 3,300 outcomes. When we look at these randomized controlled trials, what are the effects for behavioral interventions on social, emotional, or challenging behavior outcomes, developmental interventions, what they call naturalistic developmental behavioral interventions, which I was so floored by that term I had to look it up. I’m just going to tell everybody that what that is, is those kinds of interventions that are implemented in natural settings that involved shared control between the child and the person who is conducting the intervention.
They also looked at language and play. Basically, they found out that after they took out caregiver- or teacher-reported outcomes, which they identified as being really quite subject to bias, they only found significant effects estimated for developmental interventions on social communication, and naturalistic developmental behavioral interventions, also on social communication. Only one significant summary effect was estimated, and that was for this naturalistic developmental behavioral interventions on measures of diagnostic characteristics of autism, while adverse events were poorly monitored and they say they might possibly be common. The upshot of this paper for me was demonstrating that there is not that much evidence that is unbiased, that is reliable, that clinicians could make any recommendations based on.
Rick: Elizabeth, that’s after reviewing 252 different studies and that was my major takeaway too. I mean, it was actually very thorough. Ideally what you would like is that the overall development to be improved. As you mentioned, there were very specific interventions that hit a very specific part of the autism spectrum, but overall the studies were either poorly designed or they weren’t unbiased in terms of how they evaluated the outcome. They certainly didn’t evaluate whether there was any harm associated with it, so we have to go back to the drawing board.
Elizabeth: I just am struck by this because intervening early in childhood, if it does have a really positive impact for a child who is on the autism spectrum, gosh, they are just starting out. I mean, we want to improve outcomes for them — we’re all vested in that — and they also note that 1% to 4% of the population is affected by autism spectrum disorders, so trying to figure out what is the best thing.
Further, they note that here in the U.S. we are fond of very early intensive behavioral intervention that’s usually 20 to 40 hours of that kind of intervention per week, while in Europe, or in England anyway, it’s not that intensive. So what are the outcomes relative to those things?
Rick: They make a point as they conclude that any intervention first of all has to be effective. There ought to be some mechanism you can understand. It has to be practical. It’s got to be desirable, the benefits have to outweigh the cost, and it has to be effective.
Elizabeth: Indeed. Let’s turn now to JAMA.
Rick: For patients hospitalized with COVID-19, does intravenous vitamin C help? Vitamin C is known to modulate the immune system. It’s known to be an antioxidant and many people think that it’s really helpful when they have viral illnesses. Well, what about for patients that are hospitalized with COVID-19? Is it helpful?
This is actually two different studies. They were both randomized clinical trials. They enrolled two types of individuals: those that were hospitalized and weren’t critically ill — there were 40 different sites that did that — and then at 90 sites, they enrolled people that were critically ill. In both of those groups, they were randomized to either receive vitamin C given intravenously every 6 hours for 96 hours, or placebo.
How many days were they alive and then free of needing any organ support in the ICU setting up to 3 weeks after the intravenous therapy was administered? They stopped the trial early because when they looked at the interim analysis, there was no benefit at all in either group.
Elizabeth: I think it’s probably useful that we’re still looking at these things, even though we do have now a wealth of interventions that have been proven to be efficacious in both keeping people out of the hospital, helping them not to progress to needing ICU-level stays, and also from death. It’s sort of unsurprising that vitamin C isn’t helpful. We have assessed it before in the critical care setting as well as in all the rest of us, and it doesn’t really seem to demonstrate much in the way of benefit.
Rick: No, and what you’d like to do Elizabeth is, as you mentioned, people benefit from steroids if administered early on in the disease process, and 95% of these individuals in the study were receiving steroids. But you’d like to have something else that has a different mechanistic approach. If vitamin C had worked, it would be nice to add it to other things that we know are beneficial.
Elizabeth: Finally, let’s turn to The Lancet. This takes a look at what they call deferred cord clamping — that’s clamping the umbilical cord at birth; cord milking, where they try to milk the contents of the umbilical cord down into the baby, and immediate cord clamping. In this case, they’re looking at preterm births in children who were born before 37 weeks of gestation, and this is a review and meta-analysis.
They found 48 randomized trials, data on 6,300+ infants. They looked at this deferred cord clamping — waiting a little while before they clamped it — compared with this immediate, and then does this reduce death before discharge.
For umbilical cord milking compared with immediate cord clamping, there was no clear evidence of reducing death before discharge. That was also true for umbilical cord milking compared with deferred cord clamping.
They did find that waiting to clamp the cord did have a benefit with regard to allowing these infants to remain alive before discharge. They say they have high-certainty evidence that deferred cord clamping, compared with immediate cord clamping, reduces death before discharge in these preterm infants. This was something that they had already seen in full-term infants and so the question was, “Are we going be able to do this in these babies if they’re born prematurely?”
They note that there are 13 million infants worldwide who are born preterm and of these, nearly 1 million of them die. Those that survive do also incur high morbidity and healthcare costs, so is it good to defer this cord clamping for 60 seconds? And it sure looks like it was helpful.
Rick: I’m going to put some numbers to that, because it not only reduced the death rate — it reduced it by 32%. It’s just waiting to cut the cord for 60 seconds and that’s, gosh, pretty easy to do.
Now, typically you ask, “What’s the downside?” Well, the baby is a little bit more hypothermic. They are like 0.13°C cooler and the way to take care of that is you put them in a blanket. We always like to say, is there a plausible mechanism about why that could be beneficial? The hypothesis is, it obviously increases maternal blood to the infant. It may actually stabilize the transition as the baby goes from what’s fetal to neonatal circulation. There may be some mechanism by which this deferred cord clamping allows the baby to start breathing, aerate the lungs and oxygenate the blood earlier.
Elizabeth: One of the things they speculate on is that physicians may be reluctant to allow this cord to remain intact in what is frequently the chaos of a preterm infant’s birth. They think it’s going to require a behavior change.
They do also note that they have a companion network meta-analysis, also in The Lancet, that shows a dose-response effect of longer deferral, more than 2 minutes, leading to larger reductions in death before discharge. I mean, I’m just really speculating on, “Gosh, if we sort of got out of the way and didn’t impose all these interventions on this particular aspect of birth, would that even be better?”
Rick: Elizabeth, again, to put a number to it, we said that if you just delay it for 60 seconds you reduce mortality by 32%. When you delay it by more than 2 minutes, it reduced mortality by 69% in preterm infants. That’s pretty remarkable.
Elizabeth: Again, this sounds like something that’s a change in practice that’s just calling out to be implemented.
Rick: Yep, it sounds pretty easy.
Elizabeth: Okay. 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.