Infant Fever – PediaCast 305

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Dr Dan Cohen and Dr Prashant Mahajan join Dr Mike in the PediaCast Studio to discuss traditional and emerging technologies in the evaluation and management of young infants with fever. We’ll answer the usual questions surrounding baby fever: how high is too high and when should you call your doctor? In addition, advanced topics include molecular assays, polymerase chain reactions, microarray analysis and biosignatures. Be sure to stop by!

Topics

  • Infant Fever
  • How High is Too High?
  • When and How Should Baby Fever Be Treated?
  • When To Call Your Doctor
  • Traditional Methods of Fever Management
  • Emerging Technologies for Fever Management
  • Molecular Assays
  • Polymerase Chain Reactions
  • Microarray Analysis
  • Biosignatures

Guests

Links

Transcription

Announcer 1: This is PediaCast.

[Music]

Announcer 2: Welcome to Pediacast, a pediatric podcast for parents. And now, direct from the campus of Nationwide Children's, here is your host, Dr. Mike.

Dr. Mike Patrick: Hello, everyone, and welcome once again to PediaCast. It's a pediatric podcast for moms and dads. This is Dr. Mike, coming to you from the campus of Nationwide Children's Hospital on Columbus, Ohio. It is Episode 305 for December 17th, 2014. We're calling this one "Infant Fever". I want to welcome everyone to the show.

It's our last program of 2014, and it's a pretty big one. We're going to wrap up the year with the nuts and bolts program on fevers and babies. It's one of the most common reasons that new parents call their doctor or take their baby to the doctor or an urgent care center, or an emergency department — because their child has a fever.

Why do babies get fever? And how high is too high? Should they be treated, and when should you call your doctor and/or have your child seen? So those are the basic questions, the ones most moms and dads want to know the answers to, but of course, the PediaCast crowd always wants to know more. We have many science techies in the crowd along with the medical and nursing students, residents and fellows, pediatricians, family practice doctors, nurse practitioners.

For those of you who like to know more and you want to learn more, I have a special treat for you today. We're not only going to cover the surface of fevers and babies, but we're going to dive deep and talk about traditional strategies for working up and managing fevers and babies, along with the emerging technologies that may soon transform the way that we think and deal with infantile fever – things like molecular assays, polymerase chain reactions, microarray analysis and biosignatures. Yes, it's technical, but in our usual fashion, we're going to break it down into terms everyone can understand.

0:02:14

To help me do that, I have two great guests in the studio today, Dr. Dan Cohen is a pediatric emergency medicine physician here at Nationwide Children's Hospital, and Dr. Prashant Mahajan is Division Chief and Research Director of Pediatric Emergency Medicine at the Children's Hospital of Michigan. We'll get the formal introductions in a few minutes.

First here, in the end of 2014, I have an exciting announcement for you and regarding 2015 and the future of PediaCast. There's always been a pull for me on this program. My first love is teaching moms and dads and covering news parents can use, answering your questions and talking with pediatric experts about the diseases and conditions that affect your children. But on the other hand, and as we talk with Dr. Donna Caniano a couple of episodes back, educating medical professionals from students to residents to practicing doctors, that's important, too. And the pull is exactly how to keep things simple enough and interesting for parents while at the same time, covering topics deep enough to be useful for the providers in the crowd. Hence, in this episode, we're going to talk about what defines a fever and how to treat it, while also covering microarray analysis and biosignatures.

Well, never fear, I have a solution. It's a solution I thought about and really kind of been on my wish list for a long time. What I didn't have was the time or the funding to make it happen, but thanks to the good folks at Nationwide Children's Hospital, 2015 is the year to put the plan into action.

I'm excited to share with you this news, that early 2015, we'll see the creation of a brand new podcast. We're going to call it "PediaCast CME". That's right, it's a podcast for pediatric providers. We're going to kick the science up a notch and we'll end up offering Category 1 CME credit as well. PediaCast, in its current form, will continue for moms and dads, and PediaCast CME will come alongside to offer Category 1 Continuing Medical Education credits for students, nurses, residents, fellows, doctors and other professional pediatric practitioners. It's exciting news and I'll have more details for you when PediaCast returns after the New Year.

0:04:27

Friendly reminder, we do have a sibling blog over at 700Childrens.org and some recent topics there. This one is a nice blogpost from Dr. Heather Battles that it accompanies today's program. It's called "Fevers: Your Questions Answered". Be sure to check that out.

Also, "Making Connections", the role of research in deepening our understanding of motor neuron disease. One from yours truly — yes, I do write the occasional blogpost over at 700Childrens — why your toddler is hitting and biting and how to get them to stop. So be sure to check that one out.

We also have child sex behaviors, what's normal, what's not normal, when should you worry? Celebrating the holiday safely when you're child has food allergies, diabetes myths, fluoride and water, holiday poisonings, and toy dangers, also kidney stones in kids — so lots of great material there now or coming very soon to the Nationwide Children's blog, 700 Children's. Again, you can find it at 700Childrens.org.

I also want to remind you, PediaCast is your show, so if there's a topic you'd like us to talk about, just head over to PediaCast.org and click on the Contact link. Also, if you have a question for me, you can submit it there. We'll try to get your question on the show.

Also, I want to remind you, the information presented in PediaCast is for general educational purposes only. We do not diagnose medical conditions or formulate treatment plans for specific individuals. If you have a concern about your child's health, make sure you call your doctor and arrange a face-to-face interview and hands-on physical examination.

Also, your use of this audio program is subject to the PediaCast Terms of Use Agreement, which you can find at PediaCast.org.

All right, let's take a quick break and we'll get Dr. Dan Cohen and Dr. Prashant Mahajan settled in to the studio to talk about fevers and babies. That's coming up, right after this.

0:06:12

[Music]

Dr. Mike Patrick: All right, we are back.

Dr. Dan Cohen is an attending physician with the section of Emergency Medicine at Nationwide Children's Hospital and an associate professor of Clinical Pediatrics at the Ohio State University, College of Medicine. He joined me on PediaCast back in 2012 on Episode Number 209 for a discussion of pre-hospital emergency care. He's back in the studio and this time, we're talking about fevers in babies.

Thanks for joining us again, Dr. Cohen.

Dr. Dan Cohen: Thanks for having me back, Mike.

Dr. Mike Patrick: Really appreciate you stopping by.

Dr. Prashant Mahajan is here as well. He's visiting us from what we, Buckeyes, like to call the state up north. Dr. Mahajan is division chief and research director of Pediatric Emergency Medicine at the Children's Hospital Of Michigan in Detroit, and an associate professor of Pediatrics and Emergency Medicine at the Carman and Ann Adams Department of Pediatrics at the Wayne State University School of Medicine. Dr. Mahajan's research focuses on the emerging technologies and the management of infantile fevers, including microarray analysis and biosignatures. He's here to break down the meaning of those technical terms and explain how new advances have the potential to drastically change our management of fever and babies.

Let's give a warm PediaCast welcome to Dr. Prashant Mahajan. Welcome to the show.

Dr. Prashant Mahajan: Thanks, Mike. Excited to be here.

0:08:08

Dr. Mike Patrick: Great. Really, really appreciate you stopping by and coming as far as Detroit to join us here in the studio.

So, Dr. Cohen, let's start out just with the definition. What exactly defines a fever in young babies?

Dr. Dan Cohen: That is a great question, and I have the short answer, which I'll give you first. The definition of fever in young baby is a 100.4 rectal, and by young baby, for this discussion, I'd say is under three months of age. For the Canadians in the crowd and people who like Celsius, that would be 38 degrees Celsius.

Dr. Mike Patrick: Great. So 100.4 degrees Fahrenheit, 38 degrees Celsius. You talked about rectal temperature, why is it important to do a rectal temperature in babies?

Dr. Dan Cohen: Rectal temperature really is the reference standard for fever. Other techniques though can be accurate, I think, especially in very young infant, we really need to know whether or not they have a fever. There's a host of methods out there that are available, ranging from axillary, the armpit, to the forehead — temporal. But when we look at a young febrile infant, we really do need to know.

Dr. Mike Patrick: Because we're going to make some decisions on what we need to do to proceed, and so you really want that reference standard to say, "Look, this is rectal temperature that we're talking about." What about adding or subtracting a degree?

Dr. Dan Cohen: I've never been a big fan of adding or subtracting, and the other thing I would add on a practical level to family is go digital. The days of glass thermometers and mercury are gone, so go digital and go rectal. That's my two choices.

Dr. Mike Patrick: Especially for young babies. And for older kids, I always tell parents, take it how you're going to take it. Let the doctor know what number you got and how you took it, and then they can decide how they're going to interpret that.

Dr. Dan Cohen: Exactly.

Dr. Mike Patrick: Why is the presence of fever an important consideration in babies younger than three months of age?

0:10:06

Dr. Dan Cohen: Our biggest concern is that the younger a baby is, the higher risk that they have of serious bacterial infection, and that truly can be a life-threatening situation. Young babies have a less maturability to fight infections, and they also have less ability to tell us that they have a serious infection. So that signal of having a fever is extremely important for us.

Dr. Mike Patrick: It seems in babies too, that when they do get sick, things can proceed quickly. So in an older kid, you might have a fever for a few days before really, there's a big problem that's showing up, in terms of what the kids look like, sick or not sick. But in a baby, that's going to happen much faster.

Dr. Dan Cohen: Yes, as I recall form y own children, little babies that are very young, they don't do a whole lot. There isn't much of a signal to tell you that they're really sick. An older child obviously can communicate in other ways as well.

Dr. Mike Patrick: Now, what's the traditional method of working up and treating fever in babies that are less than a month old?

Dr. Dan Cohen: Internal, this is one of those principals where we would say, "Better safe than sorry." Since we know that the rates of bacterial infections are higher in the youngest infants, for those under one month or 28 days, we would in general look for infections in many places that they might show up. So we would look at their blood, their urine — especially their urine — and their spinal fluid. And that would be the initial workup, looking for that bacterial infection.

Clearly, most babies will have a viral infection, and most viral infections are reasonably well-tolerated, but it's the serious bacterial infections that concern us.

Dr. Mike Patrick: We want to take a very conservative approach when babies are less than a month of age, because those are going to be the ones that are most likely to have bad outcomes if they have a bacterial infection, and then you are figuring out that it's bacterial instead of viral. So, you're just going to basically check everywhere. Then, do those kids, for the most part, all of them get admitted to the hospital and put on antibiotics until you know for sure there's not a bacterial infection, as we practice today?

0:12:17

Dr. Dan Cohen: Yes. I would say, in general, that would be the approach. So they would be admitted to the hospital for observation and on antibiotics. Clearly, in a certain circumstance, where you have a more defined type of infection or there's other situations, one might take a different approach.

Dr. Mike Patrick: So we certainly aren't about setting standards of care for any particular community on this program, but just sort of in general, that what happens, especially when kids are less than a month of age. Now, we've kind of been going to a more of a gray area, when we hit kids who are one month of age to three months of age. Talk about what the workup for those kids with fever looks like.

Dr. Dan Cohen: Again, as babies mature, their ability to fight infection improves. And still, the most common serious bacterial infection is a urinary tract infection. So I would say across the board, that would be the first place we would look. In addition, if they have other signs or symptoms, we might look for other types of viral infections that would become the … for babies to get. In addition, there are other potential places to look, including the blood or spinal fluid if need be, depending on whether or not they look sick or if they didn't look sick. And that sort of spirals into the other question about looking for other clues for illness or not with laboratory markers.

Dr. Mike Patrick: This is one of those things where you don't want to miss any of the kids who have bacterial infections, and at the same time, in order to be cost-effective and not put kids and parents and families through more than they need to be put through, you also don't want to necessarily overdo it either. So there had been some criteria that different places come up with, like the Rochester Criteria, or Cincinnati has come up with a criteria. There's different ones that are floating out there where you look at how high the white blood cell count is, just some markers that we can hang our head on. But none of them are the same and so now, we do have sort of a situation where it's not a standard for one month-old to three-months-old as it is, where everyone can pretty much agree what you need to do under one month of age. Am I characterizing that in an appropriate fashion?

[Laughter]

0:14:30

Dr. Dan Cohen: Yes, I think that's right. There's several criterion, and even the definition of fever that we talked about a little bit earlier, those vary. Then, the biomarkers themselves like a white blood cell count that people think, "Oh, that would be a no-brainer," it's not quite too clear that's a particularly helpful marker, and I think we need to be able to move beyond that in the future.

Dr. Mike Patrick: I guess, as we talk about limitations and pitfalls of these traditional strategies, even our best efforts, there's a still a lot of kids who get admitted to the hospital, have invasive tests done, are exposed to broad spectrum antibiotics who don't need to have that happen. But because we don't want to miss anyone, we're saying we allow a lot of that to happen, when it doesn't necessarily need to.

Dr. Dan Cohen: I think that's the conversation with a parent with a febrile infant is what is the risk and what is the benefit? I think in the slightly older young infant, those risks and benefits might be a little bit different. When we say, first, do no harm, or better safe than sorry. There is potential harm in doing more. The question is how can one best stratify that risk for their family, for that specific baby.

Dr. Mike Patrick: And then, on the flip side of that, you can have a baby who clearly has a viral infection and they could have a serious bacterial infection at the same time, and so we don't want to get cavalier and say, "Oh, it's a two-and-a-half-month-old baby who has a runny nose. It's RSV season, it must be RSV, " and we send that kid home and that's the one that did have bacteria in the blood. Really, we're being pulled in two different directions in terms of trying to figure out what to do.

Dr. Dan Cohen: Yeah, it's quite clear that babies can have viral and bacterial infections at the same time. And there are some virus that probably predispose us to having secondary bacterial infection. As I told my resident friends and my medical students all the time, getting urine in my world is always correct.

[Laughter]

0:16:30

Dr. Mike Patrick: Dr. Mahajan, Dr. Cohen had talked about there's not an absolute black and white standard, especially as we look at babies who are one to three months of age. Tell us about… There was a study in The Journal of the American Medical Association back in 2004 that looked at fever management in babies. Tell us what they found in that study.

Dr. Prashant Mahajan: That's a very interesting study because they looked at children who came to the pediatricians offices across the country. They wanted to see if children who had, or infants who had fever, whether they adhere to these guidelines that Dan is talking about, and of those children who did not follow the guidelines, what was the outcome? And it appears that is an equal chance of not following the guidelines and still having a good outcome. But it ended up raising more questions than providing answers. For instance, the infants that would come to a pediatrician's office may not be a similarly ill infant or the illness profile may be different if they were to come to the ER or the emergency room.

Dr. Mike Patrick: Some parents are making the judgment call. Hey, is this a kid I can take to the pediatrician's office, or am I really worried that I'm taking him to the emergency department? So you get a bit of a different profile of your average baby that ends up in one place or the other.

Dr. Prashant Mahajan: Correct. That's correct. To the point that Dan already made ahead, because the physical examination is not clear cut, and the screening test are so non-informative to the physician. We need to look at these infants more carefully, before we decide that they can go home or do they need to be tested and treated.

0:18:18

Dr. Mike Patrick: Yeah, that's one of those, again — and we've talked about this on PediaCast several times — where you have some areas where the science of medicine really wins out, and then you have other areas where the art of medicine kind of wins out. As this study showed, for a lot of the pediatricians who were practicing in community setting, they weren't only relying on the science of medicine, but they're kind of relying on the art of medicine, and they were having good outcomes even though they may not have been following specific guidelines.

Dr. Prashant Mahajan: Absolutely. There is a gray zone which no one has yet figured out, especially in the febrile infants at this age — so what is the value of just independent clinical examination in deciding whether you need to or not need to investigate — but, again, there is such a big spectrum. Because there is so much variation, we need to have a more closer look in these infants to decide.

Dr. Mike Patrick: Yeah, absolutely. Because when it's your baby, then all bets are off. I mean, you can say well, we're going to rely on the art of medicine, we're going to go with the pediatrician's experience in dealing with little babies. But when your baby is the one who really does have a bacterial infection, you don't really want the doctor thinking it's a viral infection when it's not. This is an area where things can get bad quickly, and so we really do want some guidelines that catch everyone but don't overdo it. I think that's really where we're heading toward looking at some new technologies.

A couple of technologies that had been around for awhile are molecular assays and polymerase chain reactions. What exactly are those?

Dr. Prashant Mahajan: So all of us have cells which has our genetic material called the DNA, and that is how we transmit to the next generation. A particular way of looking at the DNA and the message that the DNA is conveying called as the RNA, those are identified by the use of these tests called molecular assays where you actually measure and quantify the amount of expression of the genes in a laboratory.

0:20:29

Dr. Mike Patrick: So you're really looking at the DNA of the organism that's causing the infection.

Dr. Prashant Mahajan: That's right.

Dr. Mike Patrick: So if you can identify that this kid has a DNA from a particular organism, then it's more likely that might be what's causing the fever.

Dr. Prashant Mahajan: Absolutely.

Dr. Mike Patrick: What are some examples of some organisms where we have tests available right now that we can run on babies? And the polymerase chain reaction is just the lab method of being able to identify that genetic material. What are some of the organisms that we can test for now?

Dr. Prashant Mahajan: Some of the common organisms, I would say the one which causes whooping cough. It's called pertussis. That is one which is very well-tested. Commonly identified viral infections like the flu viruses can be identified by this sort of assays.

Dr. Mike Patrick: RSV, respiratory syncytial virus, we've talked about on this program before. And even herpes virus which can be an issue for little babies soon after they're born, that's another one that we can do this kind of test to see if the genetic material is available. Why not then just come up, be able to identify the genetic material of more organisms than test for all of them? What's the pitfall there? What's the downside of relying on this type of technology?

Dr. Prashant Mahajan: So this is the paradigm shift that we are trying to look at, because traditionally, for years now, the people and scientists have tried to identify the presence of pathogen or the infection causing organism by looking at the DNA of that organism. But there are many instances where, one , the DNA is not available to identify but the patient could still have the infection. That is one. Or there could be an instance where the DNA just happens to be there, and the child is not even infected, but this test ends up identifying that DNA.

0:22:26

Dr. Mike Patrick: So now, we get in to false positives and false negatives. If you don't have the right fluid that has the organism in it, it doesn't mean that organism is not still in the kid's body. So if they have meningitis, let's say, an organism is in the cerebral spinal fluid, but there isn't any of it in the blood with the sample that you get, then you're not going to find it. On the other hand, they could be exposed to that, but that's not really what's making them sick at this point.

There is something out there that I came across, as I was doing some research for this particular episode called the universal polymerase chain reaction. What is that?

Dr. Prashant Mahajan: So what happens is, many organisms have a particular portion of DNA which is common to the pathogens or the organisms that cause infection and which is unique to that subgroup. So the idea of this particular test is — because it's universal — if you are able to detect this with the polymerase chain reaction, then it could be a proxy that that is the organism causing the fever or the infection.

Dr. Mike Patrick: But it's not really as specific as identifying particular organisms. So it just lets us know there are some infectious agent there but it doesn't really tell us which one.

Dr. Prashant Mahajan: That is correct. Plus, again, it doesn't welcome the issue of what do you do when you find it in an incidental patient, because all of us have some organisms already harbored in our body. What do you do then?

Dr. Mike Patrick: Absolutely. We kind of get into this newer technology or microarray analysis and biosignatures. This is really, I think, an exciting time to be in medicine, and I think that this field is really just on the verge of wanting to explode. So explain to our audience, what is exactly is a microarray analysis and how do you get a biosignature out of that?

0:24:17

Dr. Prashant Mahajan: Sure. It's exciting to talk about it, too. Again, to the previous point, you could have an infection in the body. One way to identify the infection is to go searching for the infection or the germ that is causing that, and that is what we would do with the polymerase chain reaction or a blood culture. But because of its limitations, what we are looking at is the host response or the human being's response to the presence of infection. If we can quantify that and measure that in a reliable manner, then instead of searching for the organism, why should we not consider searching for the host response and see if we are able to mount a particular response to a particular organism. Then maybe, that's an alternate way of detecting the presence of an infection.

Dr. Mike Patrick: So instead of looking for the organism itself, we're going to look to see if the body is responding in a way that's typical of a human body responding to that organism. How do you go about finding that? Where are you looking for that response?

Dr. Prashant Mahajan: So what happens is when anyone of us gets an infection, we have cells in our body called as the white blood cells which is our line of defense against any infection. What we do is we go searching for those cells, which is commonly drawn from a blood test. Then, we isolate the white blood cells and go and look for the RNA within these white cells and quantify or measure the expression of these RNA genes.

Dr. Mike Patrick: So the white blood cells are what's fighting the infection and they're going to respond in a way that's proprietary so that the white cells know what to do, and even if we don't understand exactly what it's doing. But we know that what it's doing is unique for each type of infection that it has encountered.

0:26:10

Dr. Prashant Mahajan: That's right.

Dr. Mike Patrick: I'm still trying to simplify this as best as I can.

Dr. Prashant Mahajan: Yeah, that is correct. One way to look at it, say for instance, if I had the flu, and the way my body is going to fight the flu is very similar to the way Dan's body is going fight the flu. For instance, if I had a bacterial infection like strep, my body is going to fight it in a different way, but that way is very similar as how Dan's body is going to fight strep. The point being that the body, the host, responds to a particular germ in a particular way, and we can differentiate them that.

Dr. Mike Patrick: Sure. Now, can you do that then for different viruses. If you can say, this is what the cell is doing if it's a viral infection versus if it's a strep infection. What if we're looking at influenza versus RSV, could you differentiate which virus that you're fighting based on that same technology?

Dr. Prashant Mahajan: Absolutely, I'm very glad that you asked that question because that's where the term biosignatures comes in, is we are able to now detect if it's an influenza viral infection. Then, it causes a particular signature, which is distinct and different from, say, RSV. So there is a way to identify different viruses that way.

Dr. Mike Patrick: The signature that you're talking about is encoded in the DNA that's inside the white blood cell?

Dr. Prashant Mahajan: It is encoded in the way the host responds and the way we measure it is based on the RNA, which is one outside the cell. That level of expression of the RNA is the signature. So that's how we are identifying it.

Dr. Mike Patrick: This is the RNA of the host? Of the person? Not the RNA of the organism?

Dr. Prashant Mahajan: Exactly. We are not even searching for the organism. We are looking at how the body is responding.

Dr. Mike Patrick: Right, in the person's RNA.

0:28:08

Dr. Prashant Mahajan: Exactly.

Dr. Mike Patrick: Great. Does this white blood cell that you're looking at this signature have to be in proximity to the organism that you are killing, that your body's trying to get rid of. I guess, what I'm saying is would all white blood cells in the body show this pattern while the body is fighting an infection? Or is it localized, the white blood cells just around the infection?

Dr. Prashant Mahajan: That's a great question, Mike. What happens is when the body is exposed to an infection, that is an immediate response from the white cells, would circulate. Depending upon the infection, now, certain infections like influenza could be all over the body, so if you draw the blood, you are likely to find that response everywhere. But if it was a very localized infection, then there is a potential that certain types of cells are more activated compared to others. But as a general rule of thumb, if you have an infection and the body is trying to fight, there is a very good chance that the white cells drawn would show a host response to that infection.

Dr. Mike Patrick: On the advantage side, this is a lot less invasive. You could potentially just do a little capillary stick, and get a little bit of blood and do the microarray analysis to look at the biosignature, to try to figure out which organism your body is responding to currently.

Dr. Prashant Mahajan: Correct. It is not there yet, but we could use extremely non-invasive methods, but we are rapidly progressing. With technology's progress, that it is not inconceivable, that few years from now, you could have a capillary stick or a finger stick to give you the amount of blood required.

Dr. Mike Patrick: Then, on the disadvantage side, we want to be fair to all sides, that wouldn't tell you where the infection is located. It wouldn't necessarily tell you if it's in the cerebral spinal fluid and causing a meningitis, or if it's a urinary tract infection or a blood infection, although certain organisms are going to be more likely to cause infection of different places, but it wouldn't tell you a 100% the location of the infection.

0:30:20

Dr. Prashant Mahajan: Absolutely. You brought up the right point. Certain organisms are more predisposed to reach certain organs, but the way we are thinking about this test is in the entire picture. So for instance, in the febrile infants, they are less than two months of age, so really, there is not much clinical symptoms. But conceivably, an older child would complain of urinary symptoms, for instance, and then if it would grow or demonstrate a signature that suggest to you of an organisms that grows in the urine, this is probably a faster way of identifying that.

Dr. Mike Patrick: Now, some would say this technology must come at an expense. So if you're going to incorporate this into the bedside at some point, would it be cost prohibitive? But, at the same time, you got to look at how many kids are we admitting to the hospital for overnight stays and giving them broad spectrum antibiotics? That has a cost, so I would suspect that there will be some cost savings, if you look at the whole big picture.

Dr. Prashant Mahajan: Exactly, and that is indeed one of the things that we would need to look at. But, exactly, I'm just reiterating the point that you made, that by itself this test is fairly cost prohibitor, but there are 500,000 febrile children — infants — who come to the emergency departments every year. So just imagine the cost savings and unnecessary antibiotics or hospitalization.

Dr. Mike Patrick: Absolutely. Really, research is still needed. It's ongoing. Where are you in the research of this now, and what still needs to be done?

Dr. Prashant Mahajan: So where we are right now, is we have been able to define these biosignatures, if a child or an infant has a bacterial or a non-bacterial infection, which could be viruses. We are very closed to be able to say how good this biosignature is as compared to the current reference, which is a blood culture. Where we need to be is we do need to look at it in a more robust manner, so that we can bring it to the clinical setting for the physician, and where we can give the results in four hours or six hours. That is the step where we need to be.

0:32:29

Dr. Mike Patrick: In order to do that — and folks who listen to the show knows that large prospective type studies are the ones that are most internally valid — you need a large group of patients in order to do this. Both of our hospitals are part of something called PECARN. Dr. Cohen, what is PECARN? Who are they and why is that an important thing?

Dr. Dan Cohen: PECARN stands for the Pediatric Emergency Care Applied Research Network. Did I get that right, Prashant?

Dr. Prashant Mahajan: You did, you knew.

[Laughter]

Dr. Dan Cohen: That's good.

Dr. Mike Patrick: I'm sorry. I'm asking you this, and I hadn't prepared you, but I think it's an important thing for folks to understand how research happens.

Dr. Dan Cohen: Clearly, there's no way a single center could possibly do this kind of research. Although, collectively, we see thousands of febrile infants under 60 days collectively as 16 hospitals within our consortium. Individually, there's no way we could prove that we could do it, that it could be done in a large robust way, and then moving forward to potentially apply rules. Looking down the pike, it would absolutely have to happen in a collaborative effort.

Dr. Mike Patrick: So we want to all play nice together and not be competing with one another but really work as a team to get this research done so that we can make an effect on babies' lives, sooner rather than later.

Dr. Prashant Mahajan: Absolutely, and you need an infrastructure like PECARN to explore this high-risk type of questions in a very robust manner.

0:34:11

Dr. Dan Cohen: Yup. If it wasn't for the NIH and for Maternal and Child Health and HRSA for supporting the efforts, this is probably one of the highest priority for practitioners, not just in children's hospitals but across the spectrum of the care for the children. It's one of the major high priorities for us to evaluate. I think it is a really wise investment.

Dr. Mike Patrick: Absolutely.

Dr. Mahajan, how long do you think — if you could get your crystal ball out, and we won't hold you to this — how long are we talking before we really could be using something like this? At least to differentiate between are you fighting a virus or bacteria, so that we'd have a better idea of which kids really need to admitted and antibiotics and all that.

Dr. Prashant Mahajan: I would say in the next three to four years, we would have results of very large studies that we and the few others are conducting, which would give us a very good clue on how to pursue further on this. If things were to go the way we anticipate them to go, then it is not inconceivable, then the next seven to ten years, we could potentially have a bedside test that could help in this decision-making.

Dr. Mike Patrick: That's really exciting, and not just with the biosignatures with infectious diseases, but I know this is also a way — and we just talked about this in our last episode of PediaCast — for tumor cells, being able to identify tumor cells in a similar manner by looking at a fingerprint and how your body is responding to the tumor. So you may not have to actually get a piece of the tumor and identify it, you may be able to do it just through a biosignature. This is really an exciting time. It must be great being at the forefront of this.

Dr. Prashant Mahajan: It's very exciting. Very exciting.

0:36:01

Dr. Mike Patrick: Dr. Cohen, so fever, there's a lot of fear out there. So I'm going to actually expand this now. With little babies, OK, yeah, you do need to be afraid. So if your little baby has a fever, you need to see your doctor. For older kids, there's a lot of fever fear out there. Why do kids get fevers?

Dr. Dan Cohen: Fevers, this gets in the fever phobia conversation. Fevers are evolutionary likely very helpful things for us to fight infections. At least, at home, I need to ask my wife to get a pass to actually get my daughter an ibuprofen if need be, because there is actually some benefit to having a fever. I see it more as a signal that somebody is sick. And if they're sick, then we need to try to figure out why and how sick might they be. And if they're uncomfortable or if they're not drinking adequately, or they're not going through what they need to do for their activities of daily living, then we probably should treat that fever to make people feel better.

But in and of itself, there's clearly evidence that stopping fever — at least in animals with significant infections have been done in the lab — that actually there's worst outcomes to stopping that fever. So, internal, I don't necessarily chase every fever.

Dr. Mike Patrick: Sure, and we've talked about febrile seizures on this program before and folks can do a Google search for PediaCast and febrile seizure and you'll get all the information. But really, that is not a function of a high fever causing brain damage that makes a kid have a seizure. It's not that at all. It's really more the way that a person's body responds to a change in body temperature.

Dr. Dan Cohen: That's right. It's really the rate of change. And oftentimes, parents wouldn't have noticed their child was sick until they had a febrile seizure and they are relatively common offense, of course. The average height of a fever and a febrile seizure is not particular high. It's 101, 102, so in and of itself, I don't always follow up with chasing fevers, even in the context of febrile seizures because the data is a little bit mixed about that. Again, I think it's really more a signal and treating kids for comfort.

0:38:09

Dr. Mike Patrick: Parents always ask how high is too high? And so, we're saying here 100.4 or 38 degrees Celsius if your baby's three months or younger, but for other kids, how high is too high of a fever?

Dr. Dan Cohen: That is a great question. When we look at those six or seven criterion across the board, they each have different numbers. Some people use an absolute temperature of 39 degrees Celsius or a 104 or thereabouts. The challenge with that is that kids can also have a very high fever and have influenza, and you can have a clear signal with that. The rates of SPI might be a little bit higher but the predictive value may not really be all that much to hang your head on.

Dr. Mike Patrick: So the higher the fever… Kids who have blood infection or have a serious illness are more likely to have a higher fever, but it's not an absolute thing. Certainly, you can have a very serious infection and be a 101 degrees, and you can have a cold virus and be a 104.

Dr. Dan Cohen: Yeah. Another thing I would add to that is that especially in young infants, having a low body temperature can equally be a problem. And I kind of divide fever into, you have a fever or you don't. Then, it's also age basis we've talked about, but also duration. Duration of fever can concerns us as pediatricians first.

Dr. Mike Patrick: I really like how you put that. You know you need to treat a fever if your kid is really uncomfortable with it. If their quality of life is suffering because of their fever, if you look at risk versus, it's probably your meter on risk benefit would fall on it being a benefit to treat it. But if your kids are 102 and they're running around and playing and acting OK, that's a good indication that maybe you just allow them have their fever.

Dr. Dan Cohen: Yes.

Dr. Mike Patrick: And we're not talking about any specific child here, but just in general.

[Laughter]

0:40:00

Dr. Mike Patrick: So then if you decide that you are going to treat a fever at home, how should parents treat fevers?

Dr. Dan Cohen: First, you probably covered this in the past but how to not a fever…

Dr. Mike Patrick: Yes.

Dr. Dan Cohen: We're not big fans of cold water bathing towels in the general circumstances and absolutely never using alcohol rubs like my grandma used to many years ago. That is definitely verboten. So for babies under six months, the general rule is acetaminophen. Over the six months, the choices would be acetaminophen or ibuprofen.

Dr. Mike Patrick: And no aspirin in kids because of the small risk of Reye's syndrome, unless you instructed by a doctor to use aspirin because you have something like Kawasaki Disease. There's always exceptions to the rules but in general, no aspirin.

Dr. Dan Cohen: Thank goodness, I haven't seen a case Reye's syndrome myself since the 1980s, and hopefully never will again. Clearly, that association of the non-use of aspirin is an important message to keep out there.

Dr. Mike Patrick: Acetaminophen is the active ingredients in Tylenol. In Canada, though, paracetamol, I believe, and over in Europe is the brand name. And Ibuprofen would be Advil, Motrin, those kind of names. Really, when we look at ingredients, then ibuprofen and acetaminophen are the drug names that parents should be looking for.

Dr. Prashant Mahajan: One thing I'd caution folks, and you'd probably have covered this before, Dr. Mike, is that there's so many preparations out there, reading the labels and knowing the concentration, it's really, really important.

Dr. Mike Patrick: Yeah. Now, they're putting fever reducers in some cough and cold medicines. Not that we recommend cough and cold medicines for most children, but you want to be careful that you're not giving them the same drugs in two different forms too, as well.

So when should a parent call their child's doctor about a fever? You have a kid that's got a fever. You think the fever is making him pretty lousy. You decide you're going to give him Tylenol or ibuprofen depending on their age? When should you call the doctor?

0:42:03

Dr. Dan Cohen: We've already covered under three months. I think the second cut would be, does the child look unwell or does the child look well? That would be the second kind of decision tree for me as a parent. Then, I would also think through other associated signs or symptoms, and the final thing would be duration. If the fever's going out more than three or four days, you probably should be in touch with your pediatrician.

Dr. Mike Patrick: Yup, anytime a parent wonders, "Shall I be calling my doctor? " they probably ought to call their doctor. Then, the doctor can educate them and talk to them and say well, in that situation, it's OK to give me a couple of days. You always hate the idea of a parent being worried about their child and worrying even more about what their doctors going to think of them if they call.

I mean, that's why we go into medicine. When I was in private practice, did I like getting that phone call at three in the morning? I would grumble about it, but I totally understood, and would rather have a parent call me if they're worried than not call me. Would you…?

[Laughter]

Dr. Dan Cohen: Absolutely. It kind of reminds me of back when I had my first daughter, who's now in college. She had rosy a lot. She had a fever for very prolonged period of time, until it finally broke. It's pretty anxiety-provoking to a parent with a fever and no focus, and especially the first time parents.

Dr. Mike Patrick: Yeah, and the longer it gets, you're just kind of waiting when is that fever going to stop. My daughter, she's in college as well. And I remember a time when she was young. She had a fever that lasted like seven or eight days, and you know as a doctor, we kind of used that five-day marker. When she went past that five days, it's like, "What's going on?" There is that pull of wanting to do more, but she still looked pretty good, and then it just went away, and I don't know what it was. But she's in college, so that's good.

[Laughter]

Dr. Dan Cohen: It worked out well.

Dr. Mike Patrick: Yeah. So did my bank account, but you know how that is on colleges.

All right, any other things we should be talking about with fevers in babies, before this degenerates too far down the path.

[Laughter]

0:44:11

Dr. Prashant Mahajan: I just think, to your point, it's a very exciting time to look at newer technologies, and there is a very strong possibility in the next few years, we'll get a better answer to what happens to this extremely common condition, when children is present with fever.

Dr. Mike Patrick: Great. There is some good links for you if you head to the Show Notes at PediaCast.org. Click on Show Notes and go to Episode 305, which is this one. We have the Fever Helping Hand from Nationwide Children's Hospital. We have a fever information page from HealthyChildren.org — that's organization of the American Academy of Pediatrics — and also a document from the AAP on when to call your pediatrician about a fever. And third one, from the American Academy of Pediatrics on medications used to treat fever.

So some great resources for you, if you head to the Show Notes over at PediaCast.org. We also have the Contact link to get in touch with me if you have a question for the program or you like to suggest a show topic. Then, we always have that Connect Now With The Pediatric Specialist From Nationwide Children's for referrals and appointments. You can find that in the Show Notes as well.

All right, well, big thanks to Dr. Cohen. Really appreciate you stopping by and joining us again.

Dr. Dan Cohen: Thank you for having me, Dr. Mike.

Dr. Mike Patrick: And Dr. Mahajan, thanks for traveling from Detroit. I'll say Detroit because it's not Ann Arbor, so you're a good guy.

[Laughter]

Dr. Mike Patrick: No, you would be, anyway.

Dr. Prashant Mahajan: No, I still follow the University of Michigan's footsteps.

Dr. Mike Patrick: OK, all right. You didn't tell me this before we invited him to the studio.

[Laughter]

Dr. Mike Patrick: No. Hey, it's Big Ten, and we're all Big Ten. A strong Big Ten is good for all of us.

Dr. Prashant Mahajan: It is. It is.

Dr. Mike Patrick: We really appreciate you stopping by today.

Dr. Prashant Mahajan: Thank you.

Dr. Mike Patrick: All right, let's take a quick break, and I will be back to wrap up the show, right after this.

[Music]

0:46:31

Dr. Mike Patrick: All right, well, that wraps up PediaCast for 2014. I just want to really take the time to thank each and every one of you for being a part of the audience and for making PediaCast a part of your day. I really do appreciate it, and looking forward to 2015. Again, these regular PediaCast episodes will continue and we will be adding PediaCast CME to the lineup pretty early on in 2015 for all the providers out there, so more on that to come when we get back from our holiday break.

Again, thanks to Dr. Dan Cohen, pediatric emergency medicine physician here at Nationwide Children's Hospital and Dr. Prashant Mahajan, Division Chief and Research Director of Pediatric Emergency Medicine at the Children's Hospital of Michigan.

That does wrap up our time together. PediaCast is a production of Nationwide Children's Hospital.

Don't forget PediaCast and our single-topic, short-format program, PediaBytes — we have to get clever there — they're both available on iHeart Radio Talk, which you'll find on the Web at iHeart.com and the iHeart Radio app for mobile devices.

Our show archive, which includes over 300 episodes, as well as our Show Notes, transcripts, terms of use, and our contact page are all available at the landing site, which is PediaCast.org.

We're also on iTunes, under the Kids and Family Section of their podcast directory. You'll find PediaCast on Stitcher, TuneIn, Downcast, iCatcher, Pod Bay and most other podcasting apps for iPhone and Android.

We're also on Facebook, Twitter, Google+, and Pinterest. Of course, we really appreciate you connecting with us there, and sharing, retweeting, re-pinning all of our posts so you can help spread the word about the show.

0:48:05

We also appreciate you talking us up with your family, friends, neighbors and co-workers, anyone with kids, or anyone who takes care of children. And as you're at those holiday gatherings this year, especially if you have folks with kids, make sure that your relatives or friends, associates with them, make sure you let them know about PediaCast so they can find this as well.

As always, be sure to tell your child's doctor about the program. Posters are available under the Resources tab at PediaCast.org.

Until next time, this is Dr. Mike, saying stay safe, stay healthy and stay involved with your kids. So long, everybody.

[Music]

Announcer 2: This program is a production of Nationwide Children's. Thanks for listening. We'll see you next time on PediaCast.

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