New Firearm Injury Numbers; Another Indication for Semaglutide?

— Also in TTHealthWatch: bilateral mastectomy for breast cancer

MedicalToday

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 fatal and nonfatal firearm injuries, smoking and semaglutide (Ozempic, Wegovy), bilateral mastectomy for breast cancer, and HIV in women.

Program notes:

0:41 Firearm injuries

1:41 252,000 injuries

2:40 Suffered 61.5% of firearm assaults

3:15 ?

4:15 Tobacco use disorder

5:15 Both with and without obesity

6:10 HIV prevention in women

7:10 Adolescent and young women in Africa

8:10 Coincidence of other sexually transmitted infections

8:44

9:45 According to surgical approach

10:50 About 7% recurrence regardless

11:55 Table this strategy

12:55 End

Transcript:

Elizabeth: Do we have another indication for semaglutide?

Rick: What do we know about fatal and non-fatal firearm injuries?

Elizabeth: If you have breast cancer in one breast, does it help to remove the other one?

Rick: And preventing HIV infection in women.

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, how about if we turn right to Annals of Internal Medicine? This is a look at firearms injuries and fatalities. Of course, the surgeon general is just coming out and saying, "Folks, we have a public health crisis on our hands."

Rick: We did not really know the magnitude of this previously for a couple of reasons. There is no comprehensive national data source for non-fatal firearm injuries. Second is, as you know, there hasn't been a huge amount of interest in it until recently.

Recently, the National Emergency Department Sample (NEDS) -- and by the way, that's the largest national dataset that represents acute care encounters in the United States -- began [being] able to look at their data in combination with the CDC death data. But more importantly, in 2019, they began to include race and ethnicity for the first time in their data. Now, we're able to look at not only fatal, but non-fatal firearm injuries in the United States, and also look at it by race and ethnicity.

Using this database, they looked at this information from 2019 to 2020. During this time period, there were over a quarter of a million firearm injuries, 252,000. 85,000 of those resulted in deaths. When they looked at the causes of these, about 38% were unintentional, 37% were related to assaults, 21% for self-harm, and only 1.3% were law enforcement-associated.

Elizabeth, it will probably come as no surprise that the self-harm resulted in the highest case fatality rate -- that is, 91% of those were successful in causing death. You may be surprised to know that the self-harm was highest among white persons and Native Indians, and the rate of assault was highest among Black persons. The total burden of firearm injuries amounts to an average of 1 injury every 4 minutes and 1 death every 12 minutes in the United States.

Elizabeth: Yikes. Of course, this data also reveals the disproportionate impact of this burden on people of color. I know it also breaks down age groups and how they are impacted. Would you describe some of that a little more?

Rick: Black persons make up only about 12% to 13% of the population, but they suffered 61.5% of all firearm assaults and they experienced non-fatal firearm assaults at a rate of 20-fold higher than white persons. By the way, this is particularly alarming in Black boys and men that were aged 15 to 34. Hopefully, it will drive us to change patterns and access to care that can decrease both fatal and non-fatal firearm injuries.

Elizabeth: Clearly, no one-size-fits-all kind of policy that's going to be effective here.

Rick: Yes.

Elizabeth: Staying in Annals of Internal Medicine, I said, "Do we have another indication for semaglutide?" Semaglutide, of course, is a glucagon-like peptide receptor agonist (GLP-1RA) used for the treatment of type 2 diabetes, we know, and also for the indication of obesity. Even in folks who do not have type 2 diabetes, it is effective in helping to treat obesity.

What was noticed anecdotally by many clinicians was that the folks who were taking these medicines had a reduced desire to smoke. They decided to examine in this study the association of semaglutide -- and this is a new acronym for me -- and TUD, that's tobacco use disorder. They wanted to look at that association. If you were using semaglutide, what were your TUD-related healthcare measures? I just have to note that tobacco use disorder is really applicable just by the normal use of this product, tobacco. I'm not sure that we call anything a use disorder with something else that's being used as it's intended.

They looked at a population-based database of patient electronic health records and they did that from 2017 to 2023. They were looking at comorbid type 2 diabetes and tobacco use disorder by comparing the new use of semaglutide versus 7 other diabetes medicines, and then [asked,] "Are you seeking treatment for your tobacco use disorder?"

In comparing 223,000, approximately, new users of anti-diabetes medicines, they found almost 6,000 of those folks were using semaglutide. When they did this association, it was associated with a significantly lower risk for encounters for tobacco use diagnosis. There were similar findings for those folks who both had and did not have a diagnosis of obesity. We, of course, have already agreed that we think there are huge holes in this study. You tell me what you see as a huge hole.

Rick: They said those that used semaglutide were less likely to be treated for tobacco use disorder. They were less likely to seek smoking cessation. That could be because they are smoking less. Maybe they had a reduced willingness to seek help to quit smoking. I mean, what they didn't do, what they didn't measure -- nicotine intake and the number of cigarettes consumed per day. To me, that's the biggest hole in the study. What are your thoughts, Elizabeth?

Elizabeth: That's exactly what I thought.

Rick: It's anecdotal information. They need to take it to the next step to get a better study.

Elizabeth: What we need is a big study that's got type 2 diabetes in people who smoke and are using semaglutide with a big comparator group, and measurements of metabolites of nicotine to validate that.

Rick: Elizabeth, while that study I don't consider very conclusive, I'm going to talk about one in the New England Journal of Medicine [where] I think the data are pretty compelling. This is with regard to HIV prevention in women.

Currently, women account for approximately half of the 1.3 million new HIV diagnoses that occur worldwide each year. We know that we have effective treatment for that. Since about 2000, we have actually had effective HIV pre-exposure prophylaxis (PrEP) -- daily medications that someone takes, and they are effective if they are taken as directed.

There is a novel HIV treatment drug called lenacapavir. It's a first-in-class HIV treatment. It's very potent, has a very long half-life, and therefore you can give it twice a year. Now, it's by subcutaneous injection. You inject and it forms a little nodule. Over the course of the 6 months, that nodule begins to dissolve and it releases the medication into the bloodstream. Can we use this as PrEP?

They took over 5,300 participants who were initially HIV-negative -- adolescents and young girls in South Africa and Uganda. They randomized them into one of three treatments, either the subcutaneous lenacapavir every 26 weeks; the daily PrEP that's already being used, which is called F/TDF; or another oral medication that's been effective, but has not been given as prophylaxis, called F/TAF.

The two oral medications didn't differ very substantially. They weren't terribly effective at preventing HIV because they didn't take the medications. Adherence compliance over the course of weeks and months was less than 10% or 15%. However, the injection was 100% effective in preventing HIV compared to the underlying incidence and compared to the other two medications.

Elizabeth: That's pretty amazing, isn't it? Let's talk about, what are the barriers to having this particular strategy employed?

Rick: Having access to the medication. The second is the cost.

Elizabeth: I would also like to know about the co-incidence of other STIs [sexually transmitted infections] because one thing that concerns me, of course -- and we have talked about numerous times -- is the rise in treatment-resistant gonorrhea and syphilis. I would really find it troubling if this injection would cause women to sort of turn their attention away from those things.

Rick: It doesn't address any of the bacterial infections or other viral infections.

Elizabeth: So more questions, but it sounds like a hopeful sign.

Rick: Particularly in populations with disproportionately high HIV incidence or women that have trouble getting access to care.

Elizabeth: Let's turn now to JAMA Oncology and this is an issue again we have talked about multiple times over the years. If you have breast cancer diagnosed in one breast, is it helpful to have the other one removed? We have talked about this with regard to certain subpopulations -- women with BRCA1 and 2 mutations, for example. In the wake of some rather prominent folks making this choice, it became extremely popular for women to choose bilateral mastectomy when they were diagnosed with breast cancer in one breast.

This study examines the 20-year cumulative risk of breast cancer mortality among women who were originally diagnosed with stage 0 to stage 3 unilateral breast cancer according to the type of initial surgery performed. This study used the SEER data -- that's the Surveillance, Epidemiology and End Results program -- to identify women with unilateral breast cancer, both invasive and ductal carcinoma in situ, diagnosed between 2000 and 2019.

They had 3 cohorts of equal size that they generated using their matching according to their surgical approach and then these folks were followed up for 20 years for contralateral breast cancer and for breast cancer mortality. They had in their study sample 660,000+ women. Their average age was just shy of 59 years.

After they matched them, there were 36,000+ in each of the three treatment groups. There were 766 contralateral breast cancers observed in the lumpectomy group, 728 in the unilateral mastectomy group, and 97 contralateral cancers in the bilateral mastectomy group. Overall, the risk of contralateral breast cancer was just shy of 7%. Removal of the contralateral breast did not impact on breast cancer mortality, which was essentially the same among these groups.

Rick: If there were 1,000 women with breast cancer in a single breast, over the next 20 years 69 of those 1,000 women will develop breast cancer in the other breast. Knowing that, if you did a bilateral mastectomy in the very beginning, would you affect mortality? Would you lower the risk of death in all of those 1,000 women?

The answer was no. This does not apply to individuals who have BRCA variations. The authors didn't have any information on whether the women received endocrine therapy or not, because that can actually decrease the risk of contralateral breast cancer. But what I do think the data are pretty convincing is, bilateral mastectomy did not lower overall mortality over the course of 20 years.

Elizabeth: They suggest, of course, that some women make that choice because they also want to have reconstruction that looks more symmetrical. I guess if that's a woman's primary desire when she is considering this, maybe that is worth considering, but it's pretty disfiguring and pretty traumatic surgery to undergo if it's not going to result in reduced risk and mortality.

Rick: There is a difference between doing it for cosmetic reasons as opposed to overestimating the risk of developing breast cancer in the other breast.

Elizabeth: The authors say that both previous research and this study suggest that early detection of contralateral breast cancer may not be an effective means of reducing mortality. They do talk about the follow-up and detection and that even if you catch it early, it may not actually benefit you in terms of reduction in risk of mortality.

Rick: That's disappointing news.

Elizabeth: Very disappointing, so let's table this strategy it sounds like to me, and I think I would land on that a little bit more definitively.

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.