Electronic Sepsis Alerts; Reducing Plaques in Coronary Arteries

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 electronic nudges for flu shots, reducing plaques in coronary arteries, electronic sepsis alerts, and managing cachexia in people with cancer.

Program notes:

0:40 Regression of atherosclerotic plaques

1:40 Statins or antibodies to lower cholesterol

2:41 Many respond to routine therapy

2:52 Electronic nudges for flu vaccination

3:52 Letter identifying risk

4:52 Received from Danish government

5:53 No domestic way to distribute

6:46 Cancer cachexia treatment

7:50 Change in body weight at 12 weeks

8:51 Sepsis screening in hospitalized patients

9:51 Alerts in about 15% of screening group

10:51 Identify organ dysfunction

12:13 End

Transcript:

Elizabeth: Can we use electronic nudges to get people to get a flu shot?

Rick: Addressing weight loss in people that have cancer.

Elizabeth: Monitoring for sepsis in patients in the hospital.

Rick: And how lowering cholesterol affects coronary atherosclerosis.

Elizabeth: That’s what we’re talking about this week on TT HealthWatch, 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: This is a very soft toss and I’m going to say let’s turn first to JAMA Cardiology, taking a look at, gosh, do statins actually cause regression of atherosclerotic plaques in some patients? It’s something that I have been quite interested in, because I’m a nerd, for quite a while.

Rick: Coronary atherosclerosis is pretty well known and that is the deposition of cholesterol into the wall of the blood vessels that provide nutrition to the heart. We have known for a long period of time that when you lower cholesterol, you can reduce the risk of stroke and heart attack.

There have been some trials that suggested that when we do this we can actually reduce the progression of atherosclerosis in coronary arteries. Those studies have been relatively small. The changes in atherosclerosis have been relatively modest, a 1% or 2% decrease in the blockage in coronary arteries. There are some plaques that are more prone to rupture and cause heart attacks than other ones. They oftentimes have a lot of lipid or cholesterol in the blood vessel wall. They oftentimes have a very thin cap over them, so they are more likely to rupture.

We have several ways of lowering cholesterol. Statins is one of them. They also have new antibodies, or PCSK9 inhibitors, and they are extremely effective. Well, we have a study in which we have lowered cholesterol in individuals already on a statin with one of these antibodies, alirocumab.

They looked at the coronary arteries in individuals just on statins and those that received statins and the antibody treatment. If you just use statins alone, it causes a mild amount of regression of atherosclerosis, but there is twice as much effect when you reduce cholesterol even further by using the antibody in addition. When they looked at the high-risk lesions, they were the ones that were most likely to respond and they became either medium- or low-risk.

Elizabeth: Talk to me about imaging of these high-risk lesions and how they are assessed.

Rick: Right. Now we have very sensitive instruments we can actually insert into the artery and we can look how much blockage there is, and, more importantly, what the contents are of the atherosclerosis.

Elizabeth: It sounds like we know exactly in whom they are indicated as well.

Rick: Absolutely. They are not for everybody. Many individuals respond to routine therapy with oral agents, but for those in whom they can’t either tolerate a statin or an oral agent isn’t effective in getting it down, we have alternative ways of treating that.

Elizabeth: Turning to JAMA then, let’s take a look at this idea that electronic nudges could increase influenza vaccination rates in patients who have chronic disease. This is a really interesting study as far as I’m concerned because of their randomization scheme — pretty convoluted honestly. They had quite a few ways that they were attempting to reach out to these folks.

This study is in Denmark. It enrolled all Danish citizens 18 to 64 years of age who met the criteria for free-of-charge influenza vaccination in light of their pre-existing chronic disease. These folks were already at higher risk for hospitalization or maybe even death following influenza infection because they already had these chronic diseases that were on board.

They wanted to see, “Hey, if we tweak you guys with an intervention letter, telling you there is a good reason why you ought to get this vaccination and why not consider this in light of the fact that it’s free to you, and that you have this underlying potential problem,” did more of these people step up?

I learned quite a few things about the Danish civilization as a result of this study. They had just shy of 300,000 participants who were randomized. They got this electronic intervention letter. Those who got any intervention letter, almost 40% of them stepped up, while 28% of them would have done that anyway without any intervention letter. The largest effect size was observed when they sent a repeated letter 10 days after the initial letter, and those letters that emphasized the potential cardiovascular benefits of vaccination were also really impactful.

It turns out one of the reasons why this was successful in this population is that, nationally, this is the law that when you receive these kinds of things from the Danish government you must open them and read them, and so they were able to assure that these folks were really going to get this communication.

Rick: Yeah. Elizabeth, I learned a lot about the Danish health system as well. The government in situations like this sends out both an email and a text and people have to respond. The chronic conditions we’re talking about are people that have heart disease or respiratory disease or diabetes. They were able to increase that substantially by sending out emails and texts.

Although it increased the use of vaccination in this particular age group, it didn’t decrease the rate of hospitalizations for flu and it didn’t decrease the rate of death for flu. That’s because even in these young individuals with chronic conditions, they happen relatively infrequently. Furthermore, they have done this in older individuals and about 80% of them already get the flu vaccine, so they weren’t able to see much of an incremental benefit there.

Now, the situation is very different in the United States. We have a lot of people that are concerned about immunizations and vaccines to begin with. Secondly, we don’t have a way of nationally distributing this; we have a very different health system. As you mentioned, the vaccine was given free of charge. But I still think it’s nice to know that these nudge reminders can be very helpful.

Elizabeth: They also identify a couple of other factors. They note that their population is younger, of course, in this and that they might be more responsive to these electronic nudges than older people. The other thing that they put their finger on, and I think is a really important one — and you kind of sidled around it — is this notion of trust. People in Denmark have a much higher degree of trust in the government and in their direction, particularly with regards to health outcomes, and so therefore aren’t going to question or buck the system.

Rick: Right. The results, although they are quite favorable, may not be generalizable to other countries, certainly different political norms like we have.

Elizabeth: Exactly. Let’s turn to the New England Journal of Medicine.

Rick: This is a vexing problem called cancer cachexia, weight loss. It’s fairly common among cancer patients and other chronic diseases like heart disease or liver disease. With this weight loss, people have reduced muscle mass and quality of life. It’s also associated with reduced survival.

There are some oral medications that have been used to treat it. They have unfavorable side effects. There are specific cytokines that are elevated in individuals that have cachexia. One is called growth differentiating factor-15 (GDF-15). With stress, the cytokine goes up and it acts in the hindbrain to cause people not to want to eat. As a result, it causes weight loss. We have shown this in animal models. If you inhibit it, the animals actually can gain weight. In cancer patients, this is also elevated.

They developed an antibody to it. This is a phase II trial in which patients that had cancer and that had elevated GDF-15 levels, and they administered the antibody by injection every 4 weeks for 3 doses. They looked at their change in body weight at 12 weeks. Depending upon what dose they received, there was between 3 lbs. to as much as 8 lbs.

Were there any adverse side effects? Not really. Most of the side effects were related to the fact that 90% of these people were receiving chemotherapy at the same time as they were receiving this treatment.

Elizabeth: I would also note that for those three cancers that were included in this study, there are also an awful lot of other targeted immunotherapies that are on the horizon or even in use. I’m wondering if those are going to help to overcome this issue of cachexia.

Rick: Yeah. Certainly, anything that treats the cancer can help with weight loss. There are other causes of cachexia: heart disease, chronic heart failure — cardiac cachexia is a severe problem — as well as people that have liver disease and other chronic conditions.

Elizabeth: I’m wondering about the mechanism in anorexia, for example.

Rick: That’s an interesting point. I’m not sure if GDF-15 has been measured in those individuals. Now, the other thing that this study doesn’t tell us is in what percentage of cancers is this cytokine elevated.

Elizabeth: Turning back to JAMA then, let’s take a look at this notion of sepsis screening among hospitalized patients. This was an electronic intervention — it seems like we are doing an awful lot more, I would note, about electronic interventions — looking at this electronic alert based on what’s called the Sequential Organ Failure Assessment (SOFA) score, when they looked at that in a warning that was sent to the electronic medical record for hospitalized patients.

This study was done in Saudi Arabia. Their primary outcome was 90-day in-hospital mortality and they had 11 secondary outcomes: whether they had codes that were activated, vasopressors initiated, kidney replacement therapy, multidrug-resistant organism infection, and then C. diff.

They had 60,000+ folks in this, about half of whom were in their screening group and half in the no-screening group. They had alerts occurring in about 15% of their screening group and about 18% in the no-screening group.

Those folks within 12 hours of the alert who were in the screening group were more likely to have their serum lactate tested and to have IV fluids ordered. The electronic screening did result in lower 90-day in-hospital mortality, about 15% lower. It also reduced vasopressor therapy and multidrug-resistant organisms, but increased code blues, kidney replacement therapy, and C. diff infections.

Rick: If the individual developed two of these three things — a fast heart rate, a low blood pressure, or an altered mental status — it sent an alert to the nurse. It sent an alert to the doctor. The two had to communicate with one another so that the patient could be evaluated.

The thought is you will find individuals that have early signs of infection and you’ll be able to quickly put them on antibiotics and treat them. But what these alerts do is they don’t really identify infection; they identify organ dysfunction. Most of the individuals that they identified were already on antibiotics. It increased the use of IV fluids and other medications. There was a decrease in mortality, but it didn’t really change the overall treatment of sepsis.

The editorialist wrote that it seems highly encouraging. Should this be rolled out across other health systems? Before we can confirm this, we need to talk about the nature, the accuracy, and the timeliness of the information that’s used by the alert. What’s it going to prompt you to do? There are a lot of things that go into this, other than just having an electronic medical alert, to assure that it actually benefits patients.

Elizabeth: I think that also, even within the paper, they make an interesting point where they say the reduction in mortality was observed consistently among patients with or without documented infection, suggesting that the screening effect was not limited to patients with sepsis.

Rick: Right. What you identified is a person that’s getting sicker. What it involved was going to see that patient and determining what that patient needed. More often than not, it was IV fluids.

Elizabeth: 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.