JAMA Editors’ Choice 2024: Clinical Reviews Podcasts
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Hello and welcome to this JAMA Clinical Reviews podcast. I'm Dr. Mary McDermott, Deputy Editor of JAMA. And I'm Dr. Kristen Walter, Deputy Editor of JAMA. There were 60 episodes of the Clinical Reviews podcast published in 2024. JAMA Clinical Reviews are among the most popular of the 20 shows published by the JAMA Network.

To explore all of our shows, visit jamanetworkaudio.com or search JAMA Network wherever you get your podcasts. To wrap up 2024, we've chosen three JAMA clinical review podcast conversations that were particularly noteworthy.

First up is a conversation I had with author Dr. Robert Kushner of Northwestern University's Feinberg School of Medicine on the topic of obesity medications, which JAMA published in July. Obesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity.

The FDA has approved three nutrient-stimulated hormone-based anti-obesity medications, liraglutide, semaglutide, and terzepatide. These three anti-obesity medications affect underlying appetite dysregulation, achieving and sustaining greater weight loss than other available medications.

In this JAMA podcast, Dr. Robert Kushner discusses the mechanisms by which these drugs work, their typical efficacy, and how to minimize adverse effects associated with their prescription. I asked Dr. Kushner how he selects from among the three available anti-obesity medications that are nutrient-stimulated hormone-based drugs and their typical efficacy.

Currently, Mary, because of the difficulty and shortage in access and affordability is what you can get your hands on regarding the patient and the clinician. But if we put access and affordability and shortages aside, they are particularly semaglutide and trisapatide are highly effective and individuals would generally be benefited by either of these two-letter medications.

For example, with semaglutide, individuals lose on an average of 11.5% more than placebo or comes out to about a 15% weight loss. Terzepratide is even more effective. It's about a 12.5% increased weight loss versus placebo or an average weight loss of 20%. So both of them are highly effective and have multiple benefits beyond weight loss alone.

I also asked him about how to manage adverse effects from these drugs. Side effects are primarily gastrointestinal, such as nausea, diarrhea, constipation, could be vomiting or even abdominal pain. They are temporary and are generally considered mild or perhaps moderate.

We mitigate these side effects by doing a slow dose escalation in order to ramp up to the therapeutic dose. And it's given once a week, and we increase the medication every four weeks. That's what the package insert recommends, and that's what was done in the phase three trials.

But when we're seeing a patient, we do not need to escalate at the same timeline. We can slow the escalation if they're having side effects. And equally important is to counsel the patient on a healthy diet. We have learned through the phase three trials that by choosing smaller meals, by reducing the amount of fat in meals and greasy foods, and keeping individuals well hydrated and planning your meal plan,

pattern, we can significantly reduce these side effects and increase the likelihood we'll be able to titrate them up to a therapeutic dose. I asked Dr. Kushner to discuss considerations about long-term use and considerations regarding discontinuing the drugs.

This is probably the most important decision-making between the patient and the clinician at this point. We know from the phase three trials with semaglutine-trucepidide that by suddenly stopping the medication, because that's how these trials were done, individuals regained one-half to two-thirds of the lost body weight over the subsequent half a year to a year.

So that's not a good idea. Current research is investigating other therapies such as intermittent use where you would take the dose perhaps every other week. Other therapies are looking at reducing the dose to a minimally effective dose. Others may actually be substituting or using another medication such as an oral medication that may be more cost-effective.

We also need to be emphasizing the importance of lifestyle by watching the calories, increasing exercise, particularly resistance training and aerobic activity because we want to preserve our muscle mass, and use the strategies that we've talked about for decades.

planning your meal, monitoring your body weight, tracking your steps, setting up an environment in your home and workplace so enticing foods are not as available, and monitoring your diet. And I want to return to this issue of long-term use. Is your practice to try to taper people down on dose or get them to intermittent use, or do you think it's okay for people who would like to continue semaglutide long-term to do so?

Yeah, it's an excellent question, Mary, and there's two points to come to mind. One is we currently consider obesity a chronic progressive disease, just like we would consider diabetes or hypertension. So if we use those diseases as a comparator, we think long-term treatment, right, for hypertension or diabetes. We can try and taper the dose, but we don't need to, particularly if the patient is well controlled on medications.

So we want to think the same way about obesity. If someone is tolerating medication, maintaining a lower body weight and improving their health, we may continue the medication long-term. However, efforts are on the way to really answer that question. Do patients really need to be on the same dose long-term or could they be changed to another medication such as an oral medication or one that's more cost-effective?

For now, are there any safety issues long-term that one should think about that don't come up when you first are starting the medicines?

It's important to remember that semaglutide was released under a different trade name, ozembic, although it was at a lower dose in 2017 and has been used worldwide since that time. So we have a lot of patient years exposure to this drug. And as of now, no unanticipated safety signals or side effects have emerged. Certainly, we have

post-surveillance observations going on regarding the medication, but nothing has emerged that is giving us pause that the medication is unsafe to be used long-term. Next up is a conversation I had with author Dr. Jennifer Fleiss of the University of North Carolina titled Dialysis for Chronic Kidney Failure, which we published in October.

More than 3.5 million people worldwide and 540,000 individuals in the U.S. receive maintenance hemodialysis or peritoneal dialysis for chronic kidney failure. Here's a clip from Dr. Fleith discussing the differences between in-center and home dialysis. In the United States, clinic-based hemodialysis, otherwise known as in-center hemodialysis, is the most common form of hemodialysis administered.

It is typically administered three times a week for approximately four hours per treatment. However, at some clinics, patients are offered shorter or more frequent or even longer overnight treatments in a clinic, although that's less common. For home hemodialysis, again in the United States, it typically consists of short daily treatments, usually two to three hours of therapy, four to six days a week.

But it can also be prescribed as longer treatments on the order of five to seven hours, three to six days per week. And when that occurs, it's often performed at night. And moving on to peritoneal dialysis, how is this performed? And what is the difference between continuous ambulatory peritoneal dialysis and automated peritoneal dialysis?

With peritoneal dialysis, typically a glucose-based dialysis solution is instilled in the patient's abdomen. Then transperitoneal membrane diffusive and osmotic forces facilitate toxin removal, fluid removal, otherwise known as ultrafiltration, as well as electrolyte homeostasis.

The degree of the solute exchange depends on the gradient magnitudes, as well as the quality of the peritoneal membrane and the amount of the peritoneal membrane in contact with the dialysate. Typically, in the United States, patients perform peritoneal dialysis at home using machine automated exchanges, and that's called automatic peritoneal dialysis, otherwise known as APD.

In contrast, other patients may not use a machine and instead use gravity to instill and drain fluid. And that is called continuous ambulatory peritoneal dialysis, otherwise known as CAPD.

And here's a clip from Dr. Fleiss discussing factors that patients may consider when making decisions about proceeding with hemodialysis or peritoneal dialysis. So similar to the decision to start dialysis, the choice of modality is very much a shared decision-making process between clinicians, patients, and their caregivers. Things that factor into this decision may include patient preferences and goals, and

the therapy availability, as well as clinical and socioeconomic factors and cost. Oftentimes, lifestyle considerations influence modality selection. When patients do dialysis at home, either with peritoneal dialysis or home hemodialysis, they have more flexible dialysis treatment schedules, and it doesn't involve having to travel to a dialysis clinic.

On the other hand, it does require having a lot of home equipment and supplies. For end-center hemodialysis, patients have to travel to a clinic multiple times per week at a very set time, so have very little flexibility in their schedules, but they're receiving their hemodialysis in a controlled and monitored environment.

And patients weigh the pros and cons of those approaches differently, which is why it's so important that shared decision-making really be the foundation of selecting a modality. And here's Dr. Fleith discussing what primary care clinicians can do to help preserve residual kidney function in patients with chronic kidney disease. Residual kidney function is often defined as producing at least one to two cups of urine per day.

Ways that clinicians can help patients preserve their residual kidney function is to avoid prescribing nephrotoxic medications such as non-steroidal anti-inflammatory drugs, as well as avoiding intravenous iodinated contrast media unless it's diagnostically and medically essential.

We'll finish with a conversation I had with co-authors Dr. Scott Flanders of the University of Michigan and Dr. Valerie Vaughn of the University of Utah, which JAMA published in September, titled Diagnosis and Treatment of Community Acquired Pneumonia.

Community acquired pneumonia is responsible for about 740,000 hospitalizations and causes about 41,000 deaths per year in the United States.

In their JAMA Clinical Review podcast, Drs. Valerie Vaughn and Scott Flanders discuss the typical symptoms and signs associated with diagnosing community-acquired pneumonia, optimal methods of diagnosis, and currently recommended treatment of community-acquired pneumonia. I asked Dr. Flanders about the most common presenting symptoms and challenges to diagnosing community-acquired pneumonia.

So classically what we like to see for a diagnosis of pneumonia are when patients have two or more signs and symptoms and correlated radiographic findings. And the signs and symptoms we often look for and see in patients commonly are fever, tachycardia, shortness of breath, cough, and sputum production are the most common of the signs and symptoms we see in patients presenting with a concern for community-acquired pneumonia. And how do you make a definitive diagnosis?

I think the hard thing with pneumonia is that's nearly impossible to do. There is no standard for exactly how you diagnose pneumonia. In fact, if you look for an etiologic agent, you only find the bacteria or virus or fungus that causes the pneumonia in less than half of cases.

And so what that means is that you're often treating patients empirically for pneumonia based on what you think they might have as their cause. And you're kind of ruling other things out. Dr. Flanders mentioned a patient with cough and radiographic findings could be someone with pneumonia. Well, that's also the way that heart failure might present. Or, you know, you might have a patient with COPD who has an exacerbation and they come in with worsening cough and tachypnea and shortness of breath.

and maybe it's hard to tell some abnormal lung findings on a chest x-ray. That's really hard to distinguish up front. It's what often ends up happening is you end up diagnosing or over-diagnosing pneumonia or figuring out that they have pneumonia based on how they respond to therapy. What about chest x-ray? Isn't that a good way to distinguish between those different possible diagnoses?

Chest x-ray is certainly the initial test we would use on anyone with a suspicion of pneumonia, but we happen to know it is not a 100% sensitive test. Many patients end up being diagnosed with pneumonia that have an abnormal chest x-ray. And in fact, we do reference some studies that have looked at patients that have found CT abnormalities, chest tomography abnormalities of pneumonia, and only about 40% of those abnormalities were actually seen on that chest radiograph.

So it is not uncommon for a patient to have signs and symptoms without an x-ray that conclusively shows pneumonia. So if you have a patient that you think has pneumonia and their chest x-ray is normal, would you get a CT scan?

I think that's a terrific question. I will say it is not routinely done, but as we've realized how challenging it is to diagnose pneumonia, how important it is to not miss other conditions that may present looking like pneumonia. Dr. Vaughn mentioned heart failure.

There's pulmonary embolism is a very important diagnosis not to miss, as well as lung cancers, malignancies. We've increasingly used CT to confirm that diagnosis when that suspicion exists. I think that's probably more common in the hospitalized patient compared to the patient in the ambulatory or outpatient setting where I believe CT scan would be uncommon.

One of the interesting things I learned from the podcast was about how the etiology of community-acquired pneumonia has been changing.

Well, that's changed over time. It used to be that we thought of pneumonia as being a disease that was caused by bacteria. And, you know, that today is changing, especially if you think about the pandemic we all just went through. And in fact, many patients who were severely ill from COVID had COVID pneumonia. And so we know that viruses can also cause pneumonia. And in fact, they may be the most common cause of pneumonia.

pneumonia. And an epic study which looked at patients hospitalized with pneumonia and tried to identify the etiology. This is the study where fewer than half of patients were found to have an etiology, but the most common one that was found was actually viruses. And that can be things like influenza, that can be

COVID, although this study actually took place before COVID. So now that's a new etiology we have to think about. RSV, but also all of the other viruses that can cause upper respiratory infections can also cause pneumonia. So things like rhinovirus. That being said, the most common bacteria and the one that we're often trying to treat when we prescribe antibiotics is strep pneumonia, which remains the most common cause of pneumonia.

And then beyond that, if you're thinking about other bacteria you need to treat, it really depends on your patient and the severity of disease. And I think that'll come up as we talk more and more today. And even as Scott was saying, would you get a CT scan? The answer is it depends. It depends on the severity of the disease. It depends on the patient and where you're seeing them.

And the same is true when you think about what their most common etiology is. You have to think about how severe is the disease, what exposures have they had, and what are their demographics. Is this an older adult where we know that they're more likely to have bacterial infections and could have things like Legionella? Do they live in certain parts of the United States where you have to think about endemic fungi? There are lots of things that go into that conversation based on the patient.

But for your standard patient that comes in, viruses are now probably the most common cause of pneumonia and strep is your most common bacterial cause. I asked the authors about their current recommendations for first-line therapy of outpatients with community-acquired pneumonia. When we think about empiric treatment, we really have to think about, again, where are you seeing the patient? How severe is the disease? What kind of comorbidities does the patient have?

So in an outpatient that doesn't have any other comorbidities, you can start with something relatively simple and relatively narrow with few risks of side effects like amoxicillin or doxycycline. If you're starting to think about treating a patient who has comorbidities like chronic lung disease or asplenia, then at that point moving toward a broader antibiotic like an amoxicillin clavulanate or a cephalosporin plus a macrolide is probably a better choice.

So you mentioned earlier that most community-acquired pneumonia is caused by viruses. Do you always select an antibacterial treatment when you diagnose a patient with community-acquired pneumonia?

I mentioned before that we are only recently starting to learn how important viruses are in the pathogenesis and the etiology of community acquired pneumonia. And what that means is we don't actually have great evidence supporting what to do with those patients. I think the pandemic actually offered some really interesting insight. When we started in 2020 with patients coming in with COVID pneumonia, having really severe disease, everybody prescribed empiric antibiotics.

And then as time went on, we started to realize that in fact viruses themselves can cause a pretty severe immune response and you don't need a secondary bacterial infection to have severe disease from a virus. And people started moving away from prescribing empiric antibiotics for COVID-19 unless there was evidence that the patient had a bacterial infection. So they had risk factors or they developed hospital-acquired pneumonia, in which case those patients were more likely to have a

concurrent bacterial infection. So what that means right now is that there's really wide variation in practice and probably whether patients should be getting empiric antibiotics if they're known to have viral pneumonia, again, depends on how severe their pneumonia is.

In the outpatient setting, if you have someone that comes in, they test positive for COVID and they have a cough, but they're otherwise feeling pretty well, you're not going to prescribe antibiotics to that patient. If you have someone coming in in septic shock to the ICU, you're going to prescribe empiric antibiotics to that patient.

and then the patients in between are a little bit more of a gray area, probably depending on a whole host of factors. This is where biomarkers potentially play a role. If they have a negative procalcitonin, it might make you feel comfortable with not prescribing antibiotics, whereas if they have more severe disease or underlying comorbidities, you might move in the direction of prescribing empiric antibiotics.

So there's no definite right now 100% correct choice that we know of, and there's a lot of variation. And I think the areas in the middle depend a little bit on clinical nuance. We hope you've had a chance to catch up on or will revisit all the JAMA Clinical Review podcast episodes for this past year. There's a link to the full episodes that we've highlighted in this episode's description. There will be a steady stream of new JAMA Clinical Review podcast episodes coming your way in 2025.

For more of our podcasts, please visit us online at jamanetworkaudio.com or search for JAMA Network wherever you get your podcasts. This episode was produced by Daniel Morrow at the JAMA Network. All best wishes for the new year and thanks for listening.

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