Overdose Among the Opioid-Naive; Bed Nets and Malaria

TTHealthWatch 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.

This week’s topics include consumer use of home COVID test kits; malaria net use and lifespan; vitamin D, omega-3s, and autoimmune disease; and risk factors for opioid overdose among opioid-naive patients.

Program notes:

0:42 Use of home tests kits for COVID by consumers

1:44 High probability and test results

2:44 Authors made simpler instructions

3:45 Need proper instructions

4:08 Omega-3s, vitamin D and autoimmune disease

5:08 2,000 IU per day vitamin D

6:11 Well-conducted study

7:10 Opioid overdose factors in opioid-naive people

8:10 Most likely in those over 75

9:10 Relationship to suicidality

9:35 Malaria bed nets and lifespan

10:35 Use of bed nets in infants and young children

11:30 602,000 deaths due to malaria

12:56 End

Transcript:

Elizabeth Tracey: Can vitamin D and omega-3 fatty acids help you avoid autoimmune disease?

Rick Lange, MD: What are the factors associated with opioid overdose in people with their initial opioid prescription?

Elizabeth: Bed nets and malaria, and whether that impacts on how long the kids live.

Rick: And for those who get the COVID-19 self-test kits, how well do they interpret and act on the results?

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 the dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, let’s turn right to JAMA Internal Medicine. This is a look at, hmm, if you’re doing home testing just exactly how well are you interpreting those results?

Rick: This obviously is a big deal because, as you know, at least in the U.S., they’re are planning on distributing almost 600 million tests across the country. Because the thought is, if you test early and act upon the results, you can actually decrease infection rate.

All right. So how well do we really interpret it and act on these results? This is a really interesting study. They took 360 adults and they gave them situations where they would have symptoms or not, exposure or not. Based upon that, they were either high probability or low probability of being COVID-infected. Then they gave them a test result, either positive or negative, and how do they act upon the results?

Elizabeth, let me give you some of the scenarios. If you had symptoms and also known contact with COVID, we both agree that’s high exposure, high risk. Correct?

Elizabeth: Yes.

Rick: All right. With the positive test, you think, “Gosh, I got COVID.” Well, what about for a negative test?

Elizabeth: I would guess that I just hadn’t seroconverted yet.

Rick: OK, so it’s still a high probability. What if you weren’t exposed, but had symptoms, or you were exposed, but had no symptoms and the test came back negative? How would you feel about that?

Elizabeth: Under the conditions of having a known exposure where I was still asymptomatic, I probably would assume that I was infected.

Rick: Well, it’s interesting because at least a third of the people got it wrong. Now, these are a third of the people that have the test results and the instructions that are approved by the FDA that are a part of the self-test kits. A positive test people know what to do with. But a negative test, they incorrectly assume if it’s negative, even though I’m high probability, I’m okay and I don’t have to quarantine.

This sheds light onto the fact that people don’t assess the pretest probability and incorporate it into their decision-making. Furthermore, the instructions of whether to quarantine or not that are included in the self-test kits don’t adequately inform individuals.

By the way, when they read those instructions, people did worse than if they didn’t read any instructions at all. The authors made simpler instructions and people were able to follow those. But the instructions that are part of the self-home test kits, not so good.

Elizabeth: My understanding is that there was also some CDC information that was included or used to inform the development of these instructions and we’ve certainly heard a lot of criticism about the complexity of those.

Rick: That’s right and again, that that’s part of it. They could either read the instructions that accompanied it, be forwarded to the CDC guidelines, and you have to scroll through several different screens. It’s not very easy. That’s why when they did simpler instructions people were able to follow those better, but still oftentimes they misinterpreted a negative result.

These authors said a couple things. One is the self-home test kits may not be as effective as we hope because, first of all, they are not quite as sensitive as a PCR. But furthermore, people don’t properly interpret their probability of being infected. We don’t assess how good these instructions are and we need to be doing that. If we’re going to put the onus on individuals to get tested at home, we need to give them proper instructions that they can understand about whether they should be quarantined or not. Currently, we don’t usually evaluate those instructions.

Elizabeth: The other thing that is somewhat problematic about these home test kits is that they don’t allow any collection of data with regard to transmission anywhere.

Rick: You’re absolutely right. It doesn’t provide us the information that we oftentimes need to make public health decisions.

Elizabeth: The ongoing story. Let’s turn to something else that’s had a lot of confusion surrounding it in many different arenas of health, in the BMJ, a look at whether vitamin D and marine or fish omega-3 fatty acid supplementation has anything to do with the development of autoimmune disease.

First, before I even talk about this study, I’m going to ask you, in your recollection how many times you think we’ve talked about the potential benefits of vitamin D and omega-3 fatty acids.

Rick: The observational studies that look like they can be beneficial. But in carefully conducted studies, they are not. This is interesting because it is carefully conducted and it’s a prevention study, not a treatment study.

Elizabeth: This is something that’s called the VITAL study of vitamin D and omega-3s, a nationwide, randomized, double-blind, placebo-controlled study. They have almost 26,000 participants, about half and half men and women, older than or equal to 55 years for women at enrollment, or men 50 years. Their average age was actually higher.

The intervention was 2,000 IU per day of vitamin D or a matched placebo and omega-3 fatty acids, 1,000 mg per day or a matched placebo. They followed these folks for 5.3 years and they asked them to self-report all incident autoimmune disease.

They also looked at their medical records. These autoimmune diseases included rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all other autoimmune diseases that they might have been able to identify.

The vitamin D supplementation for 5 years — with or without omega-3 fatty acids — reduced the autoimmune disease by 22%, which is really tantalizing. The omega-3 fatty acids did not reach statistical significance, but did reduce it by 15%. And both treatment arms showed larger effects than the reference arm, which was the vitamin D placebo and omega-3 fatty acid placebo group.

Rick: A very well conducted study in a large group of individuals. It’s a pretty robust endpoint. We next look at, is there a biologic plausibility? We know that vitamin D regulates genes that are involved in inflammation. They affect the cells that are involved with it, the T cells, those that make antibodies as well. So there is some biologic plausibility. Vitamin D at this particular dose is non-toxic.

For all of the other studies we’ve had for putative benefits that didn’t pan out, I think this is good evidence that vitamin D in those individuals can reduce autoimmune disease. By the way, these weren’t vitamin D deficient individuals. These were people on a usual diet. This was just supplements in addition to what they would normally take by their diet.

Elizabeth: The authors note, of course, that autoimmune disease is the third leading cause of morbidity in the industrialized world and a leading cause of mortality among women, so prevention is really important.

Rick: This study of about half men and about half women, I feel like the results are fairly reliable.

Elizabeth: Let’s turn to your next one that’s in JAMA Network Open.

Rick: We’ve talked about opioid overdose before and factors associated with it. This was a study looking at the most severe complications of opioid overdose — people that have either fatal or non-fatal overdoses. It’s done in opioid-naive individuals.

These are individuals that weren’t taking it before, but usually because of a hospitalization or some chronic condition get put on it. They asked, in those individuals what is it that’s associated with opioid, either fatal or non-fatal, overdose?

They looked at over 236,000 patients, about equally divided between men and women. Of that group who were prescribed opioids and never seen them before, about 667, or 0.3%, experienced opioid overdose. Then they looked at what are the patient-related or the prescription-related factors, so that we can really try to prevent this in this vulnerable population?

Now, here is what they found. First of all, age — and you might be surprised, Elizabeth — that the age group that was most likely to experience this were those over the age of 75. They were three times more likely to experience it as people in their middle age.

Secondly, there were obviously race and ethnicity differences. It was uncommon in Asian or Pacific Islanders, even uncommon in Hispanics, but much more common in African Americans. This is all compared to Caucasians.

Patient insurance, whether they were on Medicare or Medicaid, was associated with an increased risk, medical and psychiatric comorbidities — did they have depression or substance abuse disorder, and then interestingly enough what drug they were prescribed. Compared with codeine, those who received oxycodone or tramadol had higher incidence of overdose, whereas those with hydrocodone or morphine had no difference at all. Using these risk factors should allow us to both inform individuals, to monitor them, to prevent this serious complication.

Elizabeth: I do find it really interesting that it’s these older people who seem to be susceptible to this.

Rick: There is no explanation. Like you, I’m surprised that that group was three times more likely to experience opioid overdose than those people that were middle-aged.

Elizabeth: We’re well aware of the increasing suicidality among older people, and especially among older men. I’m wondering about that factor.

Rick: Well, Elizabeth, they weren’t able to ascertain whether that was an issue or not.

Elizabeth: I guess there is more to learn about this one, especially in view of the data relative to this opioid overdose epidemic we continue to experience.

Let’s turn finally, then, to the New England Journal of Medicine, something that turns out to be really beneficial. Again, it asks a question that I probably would never have thought of, which is, what about mosquito net use in early childhood and survival to adulthood in Tanzania?

It turns out that when we take a look at the benefits of using insecticide-treated nets among those at risk for malaria, especially among really young children, some people have hypothesized that if we control this early in childhood it might delay the acquisition of functional immunity and then shift those deaths from younger to older ages.

This is data from a 22-year prospective cohort study in rural southern Tanzania. They started out with a total of 6,706 children; they ended up with just shy of 6,000 that they followed up. They asked questions from the parents and the communities about use of insecticide-treated nets among these children, and saw that about one quarter of children never slept under a treated net, one-half slept under a treated net some of the time, and the last quarter slept always under a treated net.

Then they looked at does this actually shift death to later on? The answer was, no, it doesn’t — that, in fact, the benefits of netting these kids early on and making sure they weren’t exposed to malaria actually persisted as they grew into adulthood. I, at least, am glad to see that this question is being put to rest.

Rick: Elizabeth, and you say, why are we reporting about something in Tanzania? Well, first of all, our listenership is worldwide. But, importantly, I want everybody to realize the magnitude of the problem.

In 2020, there were an estimated 228 million cases of malaria and 602,000 deaths; 80% of these occurred in children under the age of 5. In Africa, 90% of these are in the sub-Saharan area.

From 2004 to 2019, approximately 1.9 billion — that’s billion with a B — nets were distributed in sub-Saharan Africa, so that about two-thirds of households have access to them. It’s estimated that these nets have prevented more than 450 million cases of malaria over the last 15 years. This is a low-cost, highly effective mechanism for preventing malaria. And as you highlighted, it translates into prevention of malaria and increased survival even in later years as well.

Elizabeth: I would also note that malaria, at least Aedes aegypti, and other mosquito-borne diseases are likely to penetrate more into the US as we experience climate change. So I think that we need to understand a lot more about it.

Rick: We do and we need to be looking to the future about how to prevent it. As you know, we are looking at modifying mosquitoes so they have reduced survival and fertility so they are less able to transmit the parasites.

Elizabeth: On that note, 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.