COVID Clotting Risk; Monkeypox Guidelines; Cutoffs for Gestational Diabetes

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 risk of thrombosis in patients hospitalized with COVID, cutoffs for gestational diabetes, monkeypox clinical guidelines, and remote ischemic conditioning and stroke outcomes.

Program notes:

0:40 Thromboembolism in people hospitalized with COVID versus flu

1:40 60% to 100% increased risk of deep vein thrombosis or pulmonary embolism

2:40 Continue after hospitalization?

3:44 Effect of remote ischemic conditioning in stroke

4:45 Outcomes 5% improved

5:45 Have to treat 100 to improve 5

6:48 Biologic plausibility?

7:10 Treating monkeypox clinically

8:10 Lack of evidence to guide clinical decision making

8:43 Treating gestational diabetes

9:45 Several hundred in each arm

10:45 Maybe lower glucose level would help?

11:56 End

Transcript:

Elizabeth: Do we finally know when we should treat gestational diabetes?

Rick: Do people hospitalized with COVID have an increased risk of clotting in the venous and arterial system?

Elizabeth: Can something called remote ischemic conditioning help people who have had a stroke?

Rick: And what do we know about the quality of monkeypox clinical management guidelines?

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, of course, let’s turn to the COVID material that’s in JAMA.

Rick: The authors here looked at the incidence of clotting, or what’s called thromboembolism, in both the arterial system — in the arteries — and in the veins in persons with COVID-19 because the risk of that remains unclear. Secondly, it really remains unclear whether vaccination has actually altered that at all.

So a retrospective cohort study of over 41,000 patients that were hospitalized before the vaccine became available and another 44,000 patients hospitalized after the COVID-19 vaccine was available.

They compared this to individuals that were hospitalized with influenza and they measured the arterial thromboembolism — that is, the risk of acute heart attack or a stroke — and then the risk of having a clot or thromboembolism in the vein that’s manifested as either a deep vein thrombosis or pulmonary embolism within 90 days of the hospitalization.

There was in fact an increased risk of venous thromboembolism, about a 60% and as much as 100% increase in developing either a deep vein thrombosis or developing a pulmonary embolism. Compared with flu, the risk of arterial embolism was not any higher.

Now, did the vaccine change the risk of venous clots? The answer is no. It really didn’t. Compared to patients with influenza, the risk of venous thrombosis was significantly higher among patients both before vaccine, about a 60% increase, and then during vaccine availability, again about a 90% increase.

Elizabeth: This points to a problem that was recognized really early on in COVID hospitalization, the development of blood clots, and does it suggest that we ought to be providing some kind of anticoagulation for these hospitalized folks?

Rick: Elizabeth, I think it provides in fact 2 things. One is be cognizant of this and look for it. By the way, this occurs not only during the hospitalization, but in the first 90 days afterwards. Then, during a hospital stay, we have means of preventing deep vein thrombosis, the anticoagulants to prevent that, and in high-risk individuals, as you said, the question is should we continue these afterwards either using an antiplatelet agent or low-dose anti-coagulation? I think both of those are possibilities.

Elizabeth: Are you sufficiently persuaded by the data that you would offer that as advice for people post-discharge?

Rick: The risk of thromboembolism was about 5% in patients with influenza versus about 9% with COVID-19. That’s before the vaccine became available. Then afterwards, the numbers were about 10.9% [with] a vaccine.

Elizabeth: Right, and to me that sounds like maybe in folks who were hospitalized, whether that’s for the flu or for COVID, we ought to be considering this issue post-hospitalization.

Rick: Right, but, again, I would limit it to high-risk individuals. The reason is, you don’t want to be treating 100 people, 90% of whom you expose to the risk of the treatment — and there is some risk associated with it — without receiving any benefit. But I agree with you. I do think we need to at least be cognizant and make people aware of it. In high-risk individuals, who would those be? Well, people that have had a previous clot, or maybe people that are sedentary, or people who are obese.

Elizabeth: Since we’re talking about clotting issues, let’s stay in JAMA and turn to this effect of remote ischemic conditioning versus usual care on neurologic function in patients who have had an acute moderate ischemic stroke, so a stroke due to clotting.

This is a study that was conducted in China, which I will respectfully suggest would never have happened in the United States. It had 1,893 participants with acute moderate ischemic stroke. Patients were randomly assigned within 48 hours after symptom onset to receive treatment using remote ischemic conditioning. This was using a pneumatic electronic device on both upper limbs with a cycle of cuff inflation for 5 minutes and deflation for 5 minutes for 10 to 14 days, or their usual care.

This was all based on animal models and also previous research that has shown that this idea of remote ischemic conditioning — interrupting the blood supply and then letting it come back in — is beneficial in these kinds of circumstances. Sure enough, when they looked at their outcomes, they found the number of folks who came out of this episode with excellent functional outcome at 90 days was 67.4% in the ischemic conditioning group and 62% in the control group. There were slightly more adverse events in the group that underwent the remote ischemic conditioning. Many of those were things like soreness or whatever at the site of the cuff.

The authors and the editorialists pointed out that there are some limitations to this study. One of them, of course, is there is no way to blind this, but definitely put it forward as a potential for being able to help improve outcomes in these people.

Rick: For those that may not be familiar with what we call remote ischemic conditioning, it causes brief but reversible episodes of ischemia, that is, decreased blood flow, and then you restore blood flow in vascular beds not affected by the initial insult. You have to treat 100 individuals for 5 of them to receive a non-disabling outcome with this particular therapy.

The best therapy, obviously, is to establish blood flow to the brain, and we do that either with using medications to dissolve the clot or use catheters — devices to remove the clot — those are called thrombectomies, and they are much, much more effective in terms of preventing disabling stroke.

These individuals in China didn’t have those available. What I would say is this is a very modest effect and there is some controversy because this has been tried in other individuals with stroke and it hasn’t been beneficial, so this needs to be reproduced. The advantage of it is, it can be done anywhere.

Elizabeth: I just note that the editorialist talks about a consensus group that’s called STAIR, the Stroke Treatment Academic Industry Roundtable. These folks highlighted multiple pleiotropic interventions with different mechanisms of action instead of targeting a single injury pathway. That’s one reason I thought this was persuasive. For that 5% of the folks who did better using it, it was very important for them.

Rick: Right. You say is there any biologic plausibility? It may be that causing ischemia and reperfusing provides certain proteins or protective factors. At this particular point, there are hypotheses, but we really don’t know how it’s beneficial, if in fact it is. But it needs to be reproduced.

Elizabeth: Let’s turn to the British Medical Journal and this is a look at what do we know right now about treating monkeypox clinically?

Rick: Elizabeth, this is a systematic review that looked at both the availability, the scope, and the quality of what’s called monkeypox clinical management guidelines. This is globally by the way.

Most of the monkeypox has been reported in Central Western Africa. It was first reported in 1970 and several outbreaks in 2008. That means we have had decades to arrive at what should be considered clinical management guidelines.

They did a systematic review, both in 6 databases routinely used, but also did a great literature search as well — kind of off the record. These are oftentimes in foreign languages. They are in PDFs. They are not the typical databases.

Here is what they discovered. They only found 14 guidelines were included. Unfortunately, most of them were considered to be low quality and really did a very poor job of providing evidence-based clinical guidelines.

They did note the estimates from early outbreaks in Africa show that the case fatality rate ranges between 1% and 11%, but overall they identified a lack of evidence-based clinical management guidelines to guide the clinical decision-making for patients that are diagnosed with monkeypox.

Elizabeth: This clearly is pointing to a problem since we seem to be seeing more and more monkeypox cases.

Rick: Right. This is an opportunity. The CDC is attempting again to provide guidance about identifying monkeypox and then the best available treatments, isolating individuals, antiviral agents that are available, and then specific vaccinations in people that have been exposed and are considered to be at high risk.

Elizabeth: More to come on this one, no doubt. Finally, let’s turn to the New England Journal of Medicine. I said, “Gosh, do we finally know when we ought to start treating gestational diabetes?”

This is a study that took place in New Zealand. They had a total of 4,061 women who were randomized in this study for looking at their fasting plasma glucose level, an oral glucose challenge test, and then what’s this look like, your management of sugar, over hours after you take it?

The question is when do we say, “Oh, you have gestational diabetes and now we really need to start treating you or managing you more closely?” An outcome measure that’s really important here is the delivery of a really big baby, macrosomia.

They had two levels of glycemic criteria groups. The higher one allowed for higher blood sugar levels than in the lower one. There were 310 women in the lower glycemic criteria group and 124 in the higher glycemic criteria group who were actually diagnosed with gestational diabetes.

What happened as far as their infants were concerned? Virtually identical numbers of macrosomia — large-for-gestational-age infants. Other kinds of things that surrounded that were induction of labor, use of health services, use of pharmacologic agents, and neonatal hypoglycemia were more common in this lower glycemic criteria group.

Basically, I have to say that the lower one doesn’t look like it results in the beneficial outcome they were looking for, but did result in a lot of other things that had to be done for these women. I don’t think we still know the answer.

Rick: We previously looked at studies saying, “Does the earlier diagnosis help the mother or the child?” Because currently it’s recommended that mothers be screened between 24 to 28 weeks of pregnancy. Screening earlier wasn’t beneficial.

This study said, “What if we lower the set point — that is, a lower sugar level? Maybe that will improve the outcome for the mother and the child.” But this study shows that it doesn’t. Twice as many women were diagnosed with it. They went through the usual treatments, but lowering the glucose entrance criteria for making a diagnosis didn’t really help at all. I think this is actually very helpful in avoiding the diagnosis and treatment in women who otherwise it doesn’t help them or their babies.

Elizabeth: I would also respectfully suggest that this was conducted in New Zealand, where it’s largely a White population, and because we know that the incidence of diabetes and gestational diabetes is much higher in other ethnicities, I wonder just how applicable these results are to other women.

Rick: Elizabeth, that’s a good point. In fact, in all of our studies we need to look at the populations that were studied and say, “Are they representative of the population at large?” As you said, for Caucasians this may apply, but it needs to be replicated in other populations as well. That’s a good point.

Elizabeth: On that note then, that’s 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.