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Pain Creams and Gels; Reducing Delirium: It’s PodMed Double T! (with audio)

PodMed Double T is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, 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. A transcript of the podcast is below the summary.

This week’s topics include a new tetracycline class antibiotic, a look at topical pain creams and gels, attempts to reduce delirium postoperatively, and are you ever too old for statins?

Program notes:

0:36 Are you ever too old for statins?

1:37 Lowering risk of vascular events

2:32 Absolute benefit about the same

3:20 Topical compounded pain creams and gels

4:20 Avoid oral medications

5:23 A new antibiotic

6:23 Just as effective as older antibiotics

7:22 Part of the tetracycline class

7:44 Trying to reduce delirium postop

8:44 Titrate to minimize EEG disruption

9:43 National guidelines recommend and should reevaluate

10:44 Other strategies known to help

11:13 End


Elizabeth Tracey: Can we reduce postoperative delirium?

Rick Lange, MD: A new antibiotic for skin infections and pneumonia.

Elizabeth: Does it help if you get a personalized pain cream?

Rick: And are you ever too old for statin therapy?

Elizabeth: That’s what we’re talking about this week on PodMed TT, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a medical journalist at Johns Hopkins, and this will be posted on February 8th, 2019.

Rick: And I’m Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso, and I’m also Dean of the Paul L. Foster School of Medicine.

Elizabeth: I’m going to toss the ball right to you, Rick, and ask you to comment on the one you served up about, are you ever too old for statins? That was in The Lancet, taking a look at their use across the lifespan.

Rick: There have been a lot of studies that have shown statin therapy — that is lowering cholesterol — can be very beneficial in what’s called secondary prevention, that is people that already have heart disease and also in primary prevention, people that are at risk of it, but haven’t developed heart disease, and in terms of lowering the risk of heart attacks and strokes and the need for bypass surgery. But the biggest gap is in individuals over the age of 75 years of age. What these investigators did, they did a meta-analysis of 28 different studies that were large studies. They had over a thousand people in them, and they were treated with statin therapy for at least 2 years.

In these meta-analyses, it included almost 200,000 individuals. About 15,000 were over the age of 75, and they compared them to the younger individuals. Here’s what they discovered. Across all age groups, for every millimole per liter decrease in LDL, there was about a 21% [decreased] risk of what are called vascular events. A little bit less reduction in those over the age of 75, but it was still effective. That’s great news. Probably the one group where it was least effective, however, was if you were over the age of 75 and you were using it for primary prevention, that is they had no history of heart disease. It only lowered the risk by about 8%. So the answer is — to the question are you ever too old for statins? — the answer is no, even [those] over the age of 75 can receive benefit.

Elizabeth: Right, and I think that this issue of primary prevention, of course, is front and center for older folks, because just by virtue of age, people age into a predicted cardiovascular risk that would say it’s okay for you to go on a statin. However, the question is, should we put somebody with no history of an event and no objective evidence that there is an issue, on a statin?

Rick: The absolute benefit is still about the same because their risk overall is higher. Now whenever you use medications in the elderly, you have to think about things like drug-drug interactions and the life expectancy of the patient and the quality of life, their cognitive function, comorbidities, and everything. But all things considered, statin therapy can be beneficial in the elderly when you take these things into consideration.

Elizabeth: Right. And I’m going to say that I’m still going to wait for the studies to turn up that are taking a look specifically at this population for primary prevention before when I age into it, I’m going to say, “Okay, I’ll take a statin.”

Rick: I’m glad you mentioned that because there are studies specifically looking at that age population for primary prevention. When they become available, we’ll report them to our listeners.

Elizabeth: Indeed, and then we’ll already have aged into that group, maybe, and we’ll decide, “Am I actually going to take one of these things or not?” Let’s, then, turn to Annals of Internal Medicine. I thought this one was really interesting, part of the home team here at Johns Hopkins. This was a look at these specifically compounded pain creams and gels that are made for people themselves, as I said, by prescription to reduce pain.

This was a federally funded study where they looked both here and at Walter Reed at nearly 400, and they said, “Okay, are these things really helpful or not?” It turns out that this is a huge issue. They cost between $20 to thousands of dollars for a tube of a prescription topical pain cream or a gel, and they looked at the effectiveness of these things and basically found out, guess what? They are no more effective than any of the OTC things, the over-the-counter things that you can use. Certainly not worth the time and trouble in order to go and purchase them.

Rick: The rationale behind this is to try avoid some of the side effects of taking oral medications. And in these studies, they compared it to placebo and found out these compounded creams, although much more expensive, were no better than placebo. Really, I think one of the novel things was they looked at different types of pain. They looked at individuals that had neuropathic pain — that’s pain caused by damage to the nerves — and also what’s called nociceptive pain. That’s caused by harm or injury to a body part such as arthritis or a sports injury. In neither of these two circumstances was compounded medications beneficial or better than placebo. The interesting thing is when they looked at it over the course of a month, even a third of individuals that received placebo said that their pain was better.

Elizabeth: Our famous placebo effect. We’re not really surprised by that. This was actually fairly rigorous. I mean they applied the cream three times per day. They took a little entry in a diary in order to see whether it impacted on it. So I’m pretty persuaded by this study.

Rick: As I am, too. This is really a very well-done study using what were thought to be effective compound agents.

Elizabeth: Back to the drawing board. So speaking of being at the drawing board, but actually having an impact, let’s turn to the New England Journal of Medicine, a description of a new antibiotic and a couple indications for that.

Rick: This is a new tetracycline antibiotic. And you say, “Why do we need another antibiotic?” Obviously, we’re having trouble with antibiotic resistance because many of the antibiotics have been around for decades and because of their use and sometimes overuse. We’re always looking for antibiotics that are effective against more than one organism, as well. So for example, infections like skin infections are multiple organisms. They can cause skin infection. This new tetracycline is a once a day antibiotic that can be given orally or intravenously.

In each of these studies in which there were over 300 patients treated, they compared this new tetracycline antibiotic called omadacycline with what was considered state-of-the-art therapy. Either moxifloxacin for pneumonia, or for the skin infection, linezolid. In each of these studies, the new tetracycline was just as effective as these older, established antibiotics. And also, it’s not affected by some of the tetracycline resistance, so this is a new, promising antibiotic for individuals that may be affected by some antibiotic-resistant organisms currently.

Elizabeth: And I guess I don’t want to dash cold water on this because this is a really good thing. I’m glad to see that these new agents are emerging, but I’m also wondering how long will it be before resistance emerges, also?

Rick: Well, Elizabeth, we always have to stay one step ahead. And you’re right. In the past, we’ve talked about how important it is to only target organisms with antibiotics that they’re effective against to limit the duration of antibiotic therapy and to make sure we don’t give it for things that aren’t proven to be bacterial infections. This and most other antibiotics are likely to have resistance, but we certainly need to have newer antibiotics now to treat individuals that are resistant to the current antibiotics we have or have a wider spectrum. But you’re absolutely right. This is something to be concerned of in the future.

Elizabeth: Especially since it’s part of a class that already exists, tetracyclines.

Rick: It is. It doesn’t carry some of the side effects of some of the different antibiotic classes. For example, it’s not known to cause tendon problems. And this hasn’t been associated with as much C. diff. infections. There are some benefits, but you’re right. We need to target therapy and limit it to individuals who are most likely to benefit.

Elizabeth: Our final one, then, for this week is in the Journal of the American Medical Association, which I consider to be a really laudable goal. Is there some way that we can decrease delirium following an operation for older people? Having born witness to lots of delirium and seeing how both persistent and troubling it can be for everyone, the staff and the family and the patient themselves.

So this study took a look at over 1,200 patients who were older than 60 years and having major surgery. They further subdivided these patients into whether they were having cardiac or non-cardiac surgery. They also took a look at some of their history to see if they had had falls in the past and other kinds of events that may have predicted that they would have trouble. What they used was intraoperative electroencephalography to see an EEG during the operation, how much is the waveform suppressed, and can we kind of titrate the anesthesia so that we minimize that suppression?

And it turned out very disappointingly that the delirium incidence was not significantly different between these two groups. There were some other things, though, that I thought were kind of hopeful. There was the end-tidal volatile anesthetic concentration at the end. In the guided group, it was lower than in the usual-care group. The EEG suppression was significantly less, 7 versus 13 minutes in the intervention group versus the usual-care group.

So I think that there are some median measurements that are hopeful here, but clearly still point to the need for something that’s more effective, and we don’t really understand the mechanism by which delirium develops anyway. So I think we need to kind of go back to that drawing board and find out what we might be able to do to intervene.

Rick: Many of the national guidelines recommend using EEG monitoring to assess the depth of anesthesia to minimize the amount of anesthetics. The presumption is that it would limit the amount of postoperative delirium, but this study shows that it clearly doesn’t. So many of the national guidelines are going to need to go back and re-evaluate this.

But when they looked at other secondary things like the amount of anesthesia, you’re right. It did reduce the amount of anesthesia. But the things that we’re most interested in is did it lower the amount of time that someone was hypotensive? No, it really didn’t. Did it reduce 30-day mortality? No, it didn’t. Did it reduce postop delirium? No, it really didn’t. And did it affect the awareness during the surgical procedure? The answer is no, it didn’t, either. I think it’s nice to test what are considered to be time-honored guidelines. In this particular case, the EEG, although routinely used in many places, doesn’t really seem to affect outcome in a favorable way.

Elizabeth: And we need to go back to the drawing board and figure out what is it that produces delirium in these folks to begin with?

Rick: Absolutely, and we know there are some things like other medications and comorbidities and age, whether they get out of bed, sleep cycles and use of light, sounds, things like this as well. So we know that those things clearly affect postop delirium, and we need to optimize those things, and that was done in this study, by the way. Not only did they measure the EEG, but they tried to optimize other things as well to prevent it.

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.