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More COVID-19; Broader HCV Screening: It’s TTHealthWatch!

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. A transcript of the podcast is below the summary.

This week’s topics include COVID-19 update, a multi drug regimen for drug-resistant TB, biopsy of the prostate, and hepatitis C screening.

Program notes:

0:48 COVID-19 update

1:48 1.4% died

2:50 Affects adults

3:46 No objective evidence of infection in some

4:50 Use of MRI in staging prostate cancer

5:53 Both MRI guided and systematic biopsy

6:52 Lots of news about prostate cancer

7:08 Multidrug resistant TB treatment

8:08 Totally oral for 26 weeks

9:07 Drug-resistant TB has high mortality

10:13 Screening for HCV

11:12 All asymptomatic adults 18-79

12:14 Everyone must be tested

13:02 End

Elizabeth Tracey: The obligatory COVID-19 update.

Rick Lange, MD: A screening for hepatitis C.

Elizabeth: A potential treatment for multidrug-resistant tuberculosis.

Rick: And the best way to establish prostate cancer diagnosis.

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 the Texas Tech University Health Sciences Center in El Paso, where I’m also Dean of the Paul L. Foster School of Medicine. And by the way, Elizabeth, last night we celebrated our 10-year anniversary.

Elizabeth: Who celebrated their 10-year anniversary?

Rick: The medical school did, so it was an exciting time.

Elizabeth: Excellent! Congratulations and here’s to 10 more! Let’s turn to what I served up as our obligatory look at the status right now of COVID-19. An early release in the New England Journal of Medicine took a look at 1,099 patients who were obviously in China and established a number of different parameters of the infection. At this point, they were citing a total number of cases of 81,109. This, of course, is a number that’s going up all the time. They used rapid PCR on nasal and pharyngeal swabs in order to establish this diagnosis, and they used an endpoint of ICU admission, ventilation, or death to see, “All right, what happened with these folks?”

In this cohort, they found that the average age — the median age — was 47 years, 42% of whom were female among this patient group. Five percent of them went to the ICU, 2.3% ended up on a ventilator, and 1.4% died. They found that the median incubation period was 4 days and it ranged from 2 to 7 days. The most common finding that was an objective finding was ground-glass opacity on chest CT, and they also established the R0 — the number of people that somebody who is infected potentially will infect — as 2.2.

That’s where we are with regard to this cohort. Interestingly, among this early release were two perspective pieces, one by Bill Gates, calling for not just international cooperation, but international funding and a lot of public money in order to try to come up with something that’s going to be effective here. Then the other piece from Anthony Fauci, whose statistics differed, in my mind, pretty significantly from what this cohort establishes. He cites an average age of 57 years and also establishes a mortality that’s slightly lower.

Rick: This happens to be a condition that affects adults. There are very few, if any, children affected. And of the adults that develop severe complications, whether they’re in their late 40s or late 50s, almost all of them have comorbidities. Again, let’s put this in perspective regarding other pandemics we’ve seen. With regard to MERS and SARS, this is a lower mortality. With respect to flu, it’s probably a higher mortality.

With respect to infectivity, the difference between this coronavirus and the others — the others seem to be transmitted by people that had symptoms. This may be transmitted by people that have minimal or few symptoms, which make it more difficult to control. Then, as you mentioned, the one thing is the diagnosis, but the other is quickly establishing a treatment and/or a vaccine. And as Bill Gates noted in his editorial, we need to be more effective in doing that.

Elizabeth: I found one thing that was interesting about this cohort, the fact that some people had no objective evidence — that is, on chest CT — of infection.

Rick: There’s probably a very early phase where people may not have much in the way of pneumonia, but when you look at those that were hospitalized, even though the incubation period is about 4 to 7 days, they get hospitalized usually between 10 to 14 days, so there’s some progression during that time period. But you’re right. There’s an occasional person, as we reported last week, that has few or minimal symptoms and did not have a pneumonitis, did not have a lung infection. Those are the ones we’re most concerned about being “super infectors. “They may not provide it to two or three individuals. They may provide it to 10 or 20 or 30 or 40 individuals because they don’t recognize they have the disease.

Elizabeth: Many more things still to emerge and I would note that one of the things I’ve been looking for is some pretty extensive postmortem analysis and pathology, which I have not seen anywhere yet.

Rick: No, you’re right. Again, additional information that we need.

Elizabeth: Let us move on, since we’re in the New England Journal of Medicine, and take a look at something that at least, I think, has tremendous public health implications. That’s the use of MRI in the precise diagnosis of prostate cancer.

Rick: And specifically the role of MRI as being able to target specific lesions that may be suspected to be cancer. We know that prostate cancer has a variety of different aggressiveness from being very indolent to highly lethal, so establishing what the grade is is really important because that dictates the therapy. For example, people that have low-grade prostate cancer and what we call grade I, they’ve been shown in very large trials to be associated with a very low risk of cancer-related death. So you want to be able to establish how aggressive it is.

Now, typically that’s done by doing 12 systematic biopsies in the prostate. Sometimes that can overdiagnose or underdiagnose cancer, so these authors said, “What if we used MRI-guided biopsy to target the lesion? Is that better than using systematic or perhaps maybe both should be combined?” That’s a study that was done in over 2,100 men that had suspected prostate cancer, and they underwent both methods. What they found is that the cancer detection rates using just the MRI-targeted biopsy were actually significantly lower than doing the systematic biopsies for grade I cancers. It was significantly higher for grade III through V cancers.

It seemed to get the best results with actually using both techniques together. That combined biopsy led to a cancer diagnosis in an additional 10% of men that either method alone would not have detected. It led to a higher grading of cancer in about a fifth of men, and that would have changed treatment. This shows that combined biopsy leads to more detection of prostate cancer and doing MRI-targeted biopsy alone is probably not sufficient.

Elizabeth: These things, of course, are really important because this moving target of ‘How do we appropriately stage prostate cancer?’ absolutely informs what treatment will be employed going forward.

Rick: Absolutely, and so I’m glad you picked this particular one. We tend to shy away from reporting on prostate cancer because it seems to be in the news every other week, but I think this one really has the ability to more accurately identify the grading. As you said, it specifically determines how the therapy is delivered.

Elizabeth: Remaining in the New England Journal of Medicine, let’s take a look at a study looking at a combination of three oral medications for treating folks who have extensively drug-resistant tuberculosis and multidrug-resistant tuberculosis that was not responsive to treatment. Tuberculosis, of course, a worldwide killer since we’re talking about mortality. Estimates are that about 10 million+ are infected every year and a million die as a result of the infection. We know that having other coinfections along with that is common — HIV, for example — and that this multidrug-resistant or extensively drug-resistant TB is a real issue.

In this case, they studied only 109 patients and they used this combination of drugs: bedaquiline, pretomanid, and linezolid that have this bactericidal activity against tuberculosis and for which there’s little preexisting resistance. They used this combination, as I said, it was totally oral for 26 weeks in these patients who were already pretreated in some cases and had this multidrug, some of whom had the multidrug-resistant type. 90% of them appeared to have what they called a favorable outcome. They shy away from the term “cure.” They did see an expected toxic effect of the linezolid — that is peripheral neuropathy — in the majority of the patients, and also myelosuppression in about half of the patients.

The editorialists say something that I thought was really informative. They said, “Let’s look at this historically. We did have a previous three-drug treatment that also was really important in eradicating disease, and our big problem was the development of resistance, and we already saw one case of that in this study, this very small study. What are we going to do to make sure we’re monitoring for that?”

Rick: This is a really important study, because once you get drug-resistant tuberculosis, the mortality is very high. The cure of that with our current therapy is less than 20%. This three-drug treatment resulted in 90% of individuals having a favorable outcome. The three-drug treatment ends up being, really, a major advance. As you mentioned, though, it does come with some risk, but those can be followed. The drugs can be adjusted based upon those, but otherwise, the outcome is actually very poor.

Elizabeth: And what are you thinking about needing worldwide cooperation with regard to monitoring for resistance?

Rick: I think most developed countries do that. It’s the underdeveloped — those with low- or moderate-income countries — that have the most trouble both following patients and treating them appropriately. Part of the treatment — you talked about resistance — and part of that is individuals not completing the normal treatment program. If we can provide treatment so it’s low-cost and keep the duration as short as possible and monitor these patients, we’re less likely to have drug resistance. In low- and moderate-income countries, that’s frequently not available.

Elizabeth: More to come on this one, no doubt, but at least hope for many. Let’s turn to our final one. That’s in the Journal of the American Medical Association. Should we be screening everybody for hepatitis C?

Rick: Most of our listeners may not be aware that hepatitis C virus — we’re going to call it HCV for short — is the most common chronic blood-borne pathogen in the United States. It’s the leading cause of complications for chronic liver disease. Hepatitis C virus is associated with more deaths than the top 60 other reportable infectious diseases combined. That includes HIV. Unfortunately, over the last decade, cases of acute hepatitis C infection have increased approximately four-fold, primarily because of increased injection drug use.

What the U.S. Preventative Services Task Force did was they commissioned a review of the evidence of whether we should be screening for HCV, and if so, how. By the way, this is an update to its 2013 recommendations. Their recommendation now expands screening for hepatitis C, all asymptomatic adults between the ages of 18 and 79 years without known liver disease get hepatitis C screening one time. You look for an antibody in the blood. If the antibody is present, then you do additional testing. Is there active infection, not just exposure, but is there active infection?

Elizabeth: Hmm. So far, of course, getting everybody to the table and allowing themselves to be screened for HCV has not been 100% among the previous age range for whom it was recommended.

Rick: In fact, depending upon what population it is, in low-income individuals, oftentimes the screening is less than 1%. In some of our better clinics, it may be 20% or 30%, so we still have a lot of work to do. Now you say, “Well, why would we screen?” The important thing is we now have direct antiviral agents that are effective in causing a sustained virologic response — that is curing the individual of the disease — about 95% of the time. Those drugs can be administered over an 8- to 12-week period.

It’s important and I want all of our listeners healthcare providers and our listeners that aren’t healthcare providers but are consumers to ask the question, “Is everybody between the ages of 18 and 79 being screened just one time?” Now, by the way, if you have a patient or an individual that is a drug user, they should be screened more often than one time. This recommendation doesn’t say how often that should be, but again, looking for hepatitis C virus infection, knowing that we have effective cures, is really important.

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.