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Myth of the Month: Is Contrast-Induced Acute Kidney Injury Real?
A 59-year-old man presents with abdominal pain. He has a history of small bowel obstruction and diverticulitis. His medical history includes chronic kidney disease (CKD; baseline creatinine, 1.8 mg/dL), hypertension, type 2 diabetes, and depression. He had a colectomy 6 years ago for colon cancer.
He takes the following medications: Semaglutide (1 mg weekly), amlodipine (5 mg once daily), and escitalopram (10 mg once daily). On physical exam his blood pressure is 130/80 mm Hg, his pulse is 90, and his temperature is 37.2 degrees C. He has normal bowel sounds but guarding in the right lower quadrant.
His hemoglobin is 14 g/dL, his blood sodium is 136 mEq/L, his blood potassium is 4.0 mmol/L, his BUN is 26 mg/dL, and his creatinine is 1.9 mg/dL. His kidney, ureter, bladder x-ray is unremarkable.
What imaging would you recommend?
A) CT without contrast
B) CT with contrast
C) MRI
D) Abdominal ultrasound
This patient has several potential causes for his abdominal pain that imaging may clarify. I think a contrast CT scan would be the most likely to provide helpful information. It is likely that if it were ordered, there may be hesitation by the radiologist to perform the scan with contrast because of the patient’s CKD.
Concern for contrast-induced kidney injury has limited diagnostic testing for many years. How strong is the evidence for contrast-induced kidney injury, and should we avoid testing that requires contrast in patients with CKD? McDonald and colleagues performed a meta-analysis with 13 studies meeting inclusion criteria, involving 25,950 patients.1 They found no increased risk of acute kidney injury (AKI) in patients who received contrast medium compared with those who did not receive contrast; relative risk of AKI for those receiving contrast was 0.79 (confidence interval: 0.62-1.02). Importantly, there was no difference in AKI in patients with diabetes or CKD.
Ehmann et al. looked at renal outcomes in patients who received IV contrast when they presented to an emergency department with AKI.2 They found that in patients with AKI, receiving contrast was not associated with persistent AKI at hospital discharge. Hinson and colleagues looked at patients arriving at the emergency department and needing imaging.3 They did a retrospective, cohort analysis of 17,934 patients who had CT with contrast, CT with no contrast, or no CT. Contrast administration was not associated with increased incidence of AKI (odds ratio, 0.96, CI: 0.85-1.08).
Aycock et al. did a meta-analysis of AKI after CT scanning, including 28 studies involving 107,335 patients.4 They found that compared with noncontrast CT, CT scanning with contrast was not associated with AKI (OR, 0.94, CI: 0.83-1.07). Elias and Aronson looked at the risk of AKI after contrast in patients receiving CT scans compared with those who received ventilation/perfusion scans to evaluate for pulmonary embolism.5 There were 44 AKI events (4.5%) in patients exposed to contrast media and 33 events (3.4%) in patients not exposed to contrast media (risk difference: 1.1%, 95% CI: -0.6% to 2.9%; OR, 1.39, CI: 0.86-2.26; P = .18).
Despite multiple studies showing no increased risk, there is still a concern that contrast can cause AKI.6 Animal models have shown iodinated contrast can have a deleterious effect on mitochondria and membrane function.6 Criticisms of the retrospective nature of many of the studies I have shared, and the lack of randomized, controlled trials are that there may be bias in these studies, as the highest-risk patients are the ones most likely not to receive contrast. In a joint guideline from the American College of Radiology and the National Kidney Foundation, this statement was made: “The risk of acute kidney injury developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated.”7 Their recommendation was to give contrast if needed in patients with glomerular filtration rates (GFRs) greater than 30.
Myth: Contrast-induced renal injury is a concern.
Clinical impact: For CT scanning, it is OK to give contrast when needed. A conservative cutoff for contrast use would be a GFR less than 30.
Dr. Paauw is professor of medicine in the Division of General Internal Medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. McDonald JS et al. Radiology. 2013:267:119-128.
2. Ehmann MR et al. Intensive Care Med. 2023:49(2):205-215.
3. Hinson JS et al. Ann Emerg Med. 2017;69(5):577-586.
4. Aycock RD et al. Ann Emerg Med. 2018 Jan;71(1):44-53.
5. Elias A, Aronson D. Thromb Haemost. 2021 Jun;121(6):800-807.
6. Weisbord SD, du Cheryon D. Intensive Care Med. 2018;44(1):107-109.
7. Davenport MS et al. Radiology. 2020;294(3):660-668.
A 59-year-old man presents with abdominal pain. He has a history of small bowel obstruction and diverticulitis. His medical history includes chronic kidney disease (CKD; baseline creatinine, 1.8 mg/dL), hypertension, type 2 diabetes, and depression. He had a colectomy 6 years ago for colon cancer.
He takes the following medications: Semaglutide (1 mg weekly), amlodipine (5 mg once daily), and escitalopram (10 mg once daily). On physical exam his blood pressure is 130/80 mm Hg, his pulse is 90, and his temperature is 37.2 degrees C. He has normal bowel sounds but guarding in the right lower quadrant.
His hemoglobin is 14 g/dL, his blood sodium is 136 mEq/L, his blood potassium is 4.0 mmol/L, his BUN is 26 mg/dL, and his creatinine is 1.9 mg/dL. His kidney, ureter, bladder x-ray is unremarkable.
What imaging would you recommend?
A) CT without contrast
B) CT with contrast
C) MRI
D) Abdominal ultrasound
This patient has several potential causes for his abdominal pain that imaging may clarify. I think a contrast CT scan would be the most likely to provide helpful information. It is likely that if it were ordered, there may be hesitation by the radiologist to perform the scan with contrast because of the patient’s CKD.
Concern for contrast-induced kidney injury has limited diagnostic testing for many years. How strong is the evidence for contrast-induced kidney injury, and should we avoid testing that requires contrast in patients with CKD? McDonald and colleagues performed a meta-analysis with 13 studies meeting inclusion criteria, involving 25,950 patients.1 They found no increased risk of acute kidney injury (AKI) in patients who received contrast medium compared with those who did not receive contrast; relative risk of AKI for those receiving contrast was 0.79 (confidence interval: 0.62-1.02). Importantly, there was no difference in AKI in patients with diabetes or CKD.
Ehmann et al. looked at renal outcomes in patients who received IV contrast when they presented to an emergency department with AKI.2 They found that in patients with AKI, receiving contrast was not associated with persistent AKI at hospital discharge. Hinson and colleagues looked at patients arriving at the emergency department and needing imaging.3 They did a retrospective, cohort analysis of 17,934 patients who had CT with contrast, CT with no contrast, or no CT. Contrast administration was not associated with increased incidence of AKI (odds ratio, 0.96, CI: 0.85-1.08).
Aycock et al. did a meta-analysis of AKI after CT scanning, including 28 studies involving 107,335 patients.4 They found that compared with noncontrast CT, CT scanning with contrast was not associated with AKI (OR, 0.94, CI: 0.83-1.07). Elias and Aronson looked at the risk of AKI after contrast in patients receiving CT scans compared with those who received ventilation/perfusion scans to evaluate for pulmonary embolism.5 There were 44 AKI events (4.5%) in patients exposed to contrast media and 33 events (3.4%) in patients not exposed to contrast media (risk difference: 1.1%, 95% CI: -0.6% to 2.9%; OR, 1.39, CI: 0.86-2.26; P = .18).
Despite multiple studies showing no increased risk, there is still a concern that contrast can cause AKI.6 Animal models have shown iodinated contrast can have a deleterious effect on mitochondria and membrane function.6 Criticisms of the retrospective nature of many of the studies I have shared, and the lack of randomized, controlled trials are that there may be bias in these studies, as the highest-risk patients are the ones most likely not to receive contrast. In a joint guideline from the American College of Radiology and the National Kidney Foundation, this statement was made: “The risk of acute kidney injury developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated.”7 Their recommendation was to give contrast if needed in patients with glomerular filtration rates (GFRs) greater than 30.
Myth: Contrast-induced renal injury is a concern.
Clinical impact: For CT scanning, it is OK to give contrast when needed. A conservative cutoff for contrast use would be a GFR less than 30.
Dr. Paauw is professor of medicine in the Division of General Internal Medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. McDonald JS et al. Radiology. 2013:267:119-128.
2. Ehmann MR et al. Intensive Care Med. 2023:49(2):205-215.
3. Hinson JS et al. Ann Emerg Med. 2017;69(5):577-586.
4. Aycock RD et al. Ann Emerg Med. 2018 Jan;71(1):44-53.
5. Elias A, Aronson D. Thromb Haemost. 2021 Jun;121(6):800-807.
6. Weisbord SD, du Cheryon D. Intensive Care Med. 2018;44(1):107-109.
7. Davenport MS et al. Radiology. 2020;294(3):660-668.
A 59-year-old man presents with abdominal pain. He has a history of small bowel obstruction and diverticulitis. His medical history includes chronic kidney disease (CKD; baseline creatinine, 1.8 mg/dL), hypertension, type 2 diabetes, and depression. He had a colectomy 6 years ago for colon cancer.
He takes the following medications: Semaglutide (1 mg weekly), amlodipine (5 mg once daily), and escitalopram (10 mg once daily). On physical exam his blood pressure is 130/80 mm Hg, his pulse is 90, and his temperature is 37.2 degrees C. He has normal bowel sounds but guarding in the right lower quadrant.
His hemoglobin is 14 g/dL, his blood sodium is 136 mEq/L, his blood potassium is 4.0 mmol/L, his BUN is 26 mg/dL, and his creatinine is 1.9 mg/dL. His kidney, ureter, bladder x-ray is unremarkable.
What imaging would you recommend?
A) CT without contrast
B) CT with contrast
C) MRI
D) Abdominal ultrasound
This patient has several potential causes for his abdominal pain that imaging may clarify. I think a contrast CT scan would be the most likely to provide helpful information. It is likely that if it were ordered, there may be hesitation by the radiologist to perform the scan with contrast because of the patient’s CKD.
Concern for contrast-induced kidney injury has limited diagnostic testing for many years. How strong is the evidence for contrast-induced kidney injury, and should we avoid testing that requires contrast in patients with CKD? McDonald and colleagues performed a meta-analysis with 13 studies meeting inclusion criteria, involving 25,950 patients.1 They found no increased risk of acute kidney injury (AKI) in patients who received contrast medium compared with those who did not receive contrast; relative risk of AKI for those receiving contrast was 0.79 (confidence interval: 0.62-1.02). Importantly, there was no difference in AKI in patients with diabetes or CKD.
Ehmann et al. looked at renal outcomes in patients who received IV contrast when they presented to an emergency department with AKI.2 They found that in patients with AKI, receiving contrast was not associated with persistent AKI at hospital discharge. Hinson and colleagues looked at patients arriving at the emergency department and needing imaging.3 They did a retrospective, cohort analysis of 17,934 patients who had CT with contrast, CT with no contrast, or no CT. Contrast administration was not associated with increased incidence of AKI (odds ratio, 0.96, CI: 0.85-1.08).
Aycock et al. did a meta-analysis of AKI after CT scanning, including 28 studies involving 107,335 patients.4 They found that compared with noncontrast CT, CT scanning with contrast was not associated with AKI (OR, 0.94, CI: 0.83-1.07). Elias and Aronson looked at the risk of AKI after contrast in patients receiving CT scans compared with those who received ventilation/perfusion scans to evaluate for pulmonary embolism.5 There were 44 AKI events (4.5%) in patients exposed to contrast media and 33 events (3.4%) in patients not exposed to contrast media (risk difference: 1.1%, 95% CI: -0.6% to 2.9%; OR, 1.39, CI: 0.86-2.26; P = .18).
Despite multiple studies showing no increased risk, there is still a concern that contrast can cause AKI.6 Animal models have shown iodinated contrast can have a deleterious effect on mitochondria and membrane function.6 Criticisms of the retrospective nature of many of the studies I have shared, and the lack of randomized, controlled trials are that there may be bias in these studies, as the highest-risk patients are the ones most likely not to receive contrast. In a joint guideline from the American College of Radiology and the National Kidney Foundation, this statement was made: “The risk of acute kidney injury developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated.”7 Their recommendation was to give contrast if needed in patients with glomerular filtration rates (GFRs) greater than 30.
Myth: Contrast-induced renal injury is a concern.
Clinical impact: For CT scanning, it is OK to give contrast when needed. A conservative cutoff for contrast use would be a GFR less than 30.
Dr. Paauw is professor of medicine in the Division of General Internal Medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. McDonald JS et al. Radiology. 2013:267:119-128.
2. Ehmann MR et al. Intensive Care Med. 2023:49(2):205-215.
3. Hinson JS et al. Ann Emerg Med. 2017;69(5):577-586.
4. Aycock RD et al. Ann Emerg Med. 2018 Jan;71(1):44-53.
5. Elias A, Aronson D. Thromb Haemost. 2021 Jun;121(6):800-807.
6. Weisbord SD, du Cheryon D. Intensive Care Med. 2018;44(1):107-109.
7. Davenport MS et al. Radiology. 2020;294(3):660-668.
‘Green Whistle’ Provides Pain Relief -- But Not in the US
This discussion was recorded on March 29, 2024. The transcript has been edited for clarity.
Robert D. Glatter, MD: Joining me today to discuss the use of methoxyflurane (Penthrox), an inhaled nonopioid analgesic for the relief of acute pain, is Dr. William Kenneth (Ken) Milne, an emergency physician at Strathroy Middlesex General Hospital in Ontario, Canada, and the founder of the well-known podcast The Skeptics’ Guide to Emergency Medicine (SGEM).
Also joining me is Dr. Sergey Motov, an emergency physician and research director at Maimonides Medical Center in Brooklyn, New York, and an expert in pain management. I want to welcome both of you and thank you for joining me.
RAMPED Trial: Evaluating the Efficacy of Methoxyflurane
Dr. Glatter: Ken, your recent post on Twitter [now X] regarding the utility of Penthrox in the RAMPED trial really caught my attention. While the trial was from 2021, it really is relevant regarding the prehospital management of pain in the practice of emergency medicine, and certainly in-hospital practice. I was hoping you could review the study design but also get into the rationale behind the use of this novel agent.
William Kenneth (Ken) Milne, MD, MSc: Sure. I’d be happy to kick this episode off with talking about a study that was published in 2020 in Academic Emergency Medicine. It was an Australian study by Brichko et al., and they were doing a randomized controlled trial looking at methoxyflurane vs standard care.
They selected out a population of adults, which they defined as 18-75 years of age. They were in the prehospital setting and they had a pain score of greater than 8. They gave the participants methoxyflurane, which is also called the “green whistle.” They had the subjects take that for their prehospital pain, and they compared that with whatever your standard analgesic in the prehospital setting would be.
Their primary outcome was how many patients had at least 50% reduction in their pain score within 30 minutes. They recruited about 120 people, and they found that there was no statistical difference in the primary outcome between methoxyflurane and standard care. Again, that primary outcome was a reduction in pain score by greater than 50% at 30 minutes, and there wasn’t a statistical difference between the two.
There are obviously limits to any study, and it was a convenience sample. This was an unmasked trial, so people knew if they were getting this green whistle, which is popular in Australia. People would be familiar with this device, and they didn’t compare it with a sham or placebo group.
Pharmacology of Penthrox: Its Role and Mechanism of Action
Dr. Glatter: The primary outcome wasn’t met, but certainly secondary outcomes were. There was, again, a relatively small number of patients in this trial. That said, there was significant pain relief. I think there are issues with the trial, as with any trial limitations.
Getting to the pharmacology of Penthrox, can you describe this inhaled anesthetic and how we use it, specifically its role at the subanesthetic doses?
Sergey M. Motov, MD: Methoxyflurane is embedded in the green whistle package, and that whole contraption is called Penthrox. It’s an inhaled volatile fluorinated hydrocarbon anesthetic that was predominantly used, I’d say 40, 50 years ago, for general anesthesia and slowly but surely fell out of favor due to the fact that, when used for prolonged duration or in supratherapeutic doses, there were cases of severe or even fatal nephrotoxicity and hepatotoxicity.
In the late ‘70s and early ‘80s, all the fluranes came on board that are slightly different as general anesthetics, and methoxyflurane started slowly falling out of favor. Because of this paucity and then a subsequent slightly greater number of cases of nephrotoxicity and hepatotoxicity, [the US Food and Drug Administration] FDA made a decision to pull the drug off the market in 2005. FDA successfully accomplished its mission and since then has pretty much banned the use of inhaled methoxyflurane in any shape, form, or color in the United States.
Going back to the green whistle, it has been used in Australia probably for about 50-60 years, and has been used in Europe for probably 10-20 years. Ken can attest that it has been used in Canada for at least a decade and the track record is phenomenal.
We are using subanesthetic, even supratherapeutic doses that, based on available literature, has no incidence of this fatal hepatotoxicity or nephrotoxicity. We’re talking about 10 million doses administered worldwide, except in the United States. There are 40-plus randomized clinical trials with over 30,000 patients enrolled that prove efficacy and safety.
That’s where we are right now, in a conundrum. We have a great deal of data all over the world, except in the United States, that push for the use of this noninvasive, patient-controlled nonopioid inhaled anesthetic. We just don’t have the access in North America, with the exception of Canada.
Regulatory Hurdles: Challenges in FDA Approval
Dr. Glatter: Absolutely. The FDA wants to be cautious, but if you look at the evidence base of data on this, it really indicates otherwise. Do you think that these roadblocks can be somehow overcome?
Dr. Milne: In the 2000s and 2010s, everybody was focused on opioids and all the dangers and potential adverse events. Opioids are great drugs like many other drugs; it depends on dose and duration. If used properly, it’s an excellent drug. Well, here’s another excellent drug if it’s used properly, and the adverse events are dependent on their dose and duration. Penthrox, or methoxyflurane, is a subtherapeutic, small dose and there have been no reported cases of addiction or abuse related to these inhalers.
Dr. Glatter: That argues for the point — and I’ll turn this over to you, Sergey — of how can this not, in my mind, be an issue that the FDA can overcome.
Dr. Motov: I agree with you. It’s very hard for me to speak on behalf of the FDA, to allude to their thinking processes, but we need to be up to speed with the evidence. The first thing is, why don’t you study the drug in the United States? I’m not asking you to lift the ban, which you put in 2005, but why don’t you honor what has been done over two decades and at least open the door a little bit and let us do what we do best? Why don’t you allow us to do the research in a controlled setting with a carefully, properly selected group of patients without underlying renal or hepatic insufficiency and see where we’re at?
Let’s compare it against placebo. If that’s not ethical, let’s compare it against active comparators — God knows we have 15-20 drugs we can use — and let’s see where we’re at. Ken has been nothing short of superb when it comes to evidence. Let us put the evidence together.
Dr. Milne: If there were concerns decades ago, those need to be addressed. As science is iterative and as other information becomes available, the scientific method would say, Let’s reexamine this and let’s reexamine our position, and do that with evidence. To do that, it has to have validity within the US system. Someone like you doing the research, you are a pain research guru; you should be doing this research to say, “Does it work or not? Does this nonapproval still stand today in 2024?”
Dr. Motov: Thank you for the shout-out, and I agree with you. All of us, those who are interested, on the frontiers of emergency care — as present clinicians — we should be doing this. There is nothing that will convince the FDA more than properly and rightly conducted research, time to reassess the evidence, and time to be less rigid. I understand that you placed a ban 20 years ago, but let’s go with the science. We cannot be behind it.
Exploring the Ecological Footprint of Methoxyflurane
Dr. Milne: There was an Austrian study in 2022 and a very interesting study out of the UK looking at life-cycle impact assessment on the environment. If we’re not just concerned about patient care —obviously, we want to provide patients with a safe and effective product, compared with other products that are available that might not have as good a safety profile — this looks at the impact on the environment.
Dr. Glatter: Ken, can you tell me about some of your recent research regarding the environmental effects related to use of Penthrox, but also its utility pharmacologically and its mechanism of action?
Dr. Milne: There was a really interesting study published this year by Martindale in the Emergency Medicine Journal. It took a different approach to this question about could we be using this drug, and why should we be using this drug? Sergey and I have already talked about the potential benefits and the potential harms. I mentioned opioids and some of the concerns about that. For this drug, if we’re using it in the prehospital setting in this little green whistle, the potential benefits look really good, and we haven’t seen any of the potential harms come through in the literature.
This was another line of evidence of why this might be a good drug, because of the environmental impact of this low-dose methoxyflurane. They compared it with nitrous oxide and said, “Well, what about the life-cycle impact on the environment of using this and the overall cradle-to-grave environmental impacts?”
Obviously, Sergey and I are interested in patient care, and we treat patients one at a time. But we have a larger responsibility to social determinants of health, like our environment. If you look at the overall cradle-to-grave environmental impact of this drug, it was better than for nitrous oxide when looking specifically at climate-change impact. That might be another reason, another line of argument, that could be put forward in the United States to say, “We want to have a healthy environment and a healthy option for patients.”
I’ll let Sergey speak to mechanisms of action and those types of things.
Dr. Motov: As a general anesthetic and hydrocarbonated volatile ones, I’m just going to say that it causes this generalized diffuse cortical depression, and there are no particular channels, receptors, or enzymes we need to worry much about. In short, it’s an inhaled gas used to put patients or people to sleep.
Over the past 30 or 40 years — and I’ll go back to the past decade — there have been numerous studies in different countries (outside of the United States, of course), and with the recent study that Ken just cited, there were comparisons for managing predominantly acute traumatic injuries in pediatric and adult populations presenting to EDs in various regions of the world that compared Penthrox, or the green whistle, with either placebo or active comparators, which included parenteral opioids, oral opioids, and NSAIDs.
The recent systematic review by Fabbri, out of Italy, showed that for ultra–short-term pain — we’re talking about 5, 10, or 15 minutes — inhaled methoxyflurane was found to be equal or even superior to standard of care, primarily related to parenteral opioids, and safety was off the hook. Interestingly, with respect to analgesia, they found that geriatric patients seemed to be responding more, with respect to changing pain score, than younger adults — we’re talking about ages 18-64 vs 65 or older. Again, we need to make sure that we carefully select those elderly people without underlying renal or hepatic insufficiency.
To wrap this up, there is evidence clearly supporting its analgesic efficacy and safety, even in comparison to commonly used and traditionally accepted analgesic modalities that we use for managing acute pain.
US Military Use and Implications for Civilian Practice
Dr. Glatter: Do you think that methoxyflurane’s use in the military will help propel its use in clinical settings in the US, and possibly convince the FDA to look at this closer? The military is currently using it in deployed combat veterans in an ongoing fashion.
Dr. Motov: I’m excited that the Department of Defense in the United States has taken the lead, and they’re being very progressive. There are data that we’ve adapted to the civilian environment by use of intranasal opioids and intranasal ketamine with more doctors who came out of the military. In the military, it’s a kingdom within a kingdom. I don’t know their relationship with the FDA, but I support the military’s pharmacologic initiative by honoring and disseminating their research once it becomes available.
For us nonmilitary folks, we still need to work with the FDA. We need to convince the FDA to let us study the drug, and then we need to pile the evidence within the United States so that the FDA will start looking at this favorably. It wouldn’t hurt and it wouldn’t harm. Any piece of evidence will add to the existing body of literature that we need to allow this medication to be available to us.
Safety Considerations and Aerosolization Concerns
Dr. Glatter: Its safety in children is well established in Australia and throughout the world. I think it deserves a careful look, and the evidence that you’ve both presented argues for the use of this prehospital but also in hospital. I guess there was concern in the hospital with underventilation and healthcare workers being exposed to the fumes, and then getting headaches, dizziness, and so forth. I don’t know if that’s borne out, Ken, in any of your experience in Canada at all.
Dr. Milne: We currently don’t have it in our shop. It’s being used in British Columbia right now in the prehospital setting, and I’m not aware of anybody using it in their department. It’s used prehospital as far as I know.
Dr. Motov: I can attest to it, if I may, because I had familiarized myself with the device. I actually was able to hold it in my hands. I have not used it yet but I had the prototype. The way it’s set up, there is an activated charcoal chamber that sits right on top of the device, which serves as the scavenger for exhaled air that contains particles of methoxyflurane. In theory, but I’m telling how it is in practicality, it significantly reduces occupational exposure, based on data that lacks specifics.
Although most of the researchers did not measure the concentration of methoxyflurane in ambient air within the treatment room in the EDs, I believe the additional data sources clearly stating that it’s within or even below the detectable level that would cause any harm. Once again, we need to honor pathology. We need to make sure that pregnant women will not be exposed to it.
Dr. Milne: In 2024, we also need to be concerned about aerosolizing procedures and aerosolizing treatments, and just take that into account because we should be considering all the potential benefits and all the potential harms. Going through the COVID-19 pandemic, there was concern about transmission and whether or not it was droplet or aerosolized.
There was an observational study published in 2022 in Austria by Trimmel in BMC Emergency Medicine showing similar results. It seemed to work well and potential harms didn’t get picked up. They had to stop the study early because of COVID-19.
We need to always focus in on the potential benefits, the potential harms; where does the science land? Where do the data lie? Then we move forward from that and make informed decisions.
Final Thoughts
Dr. Glatter: Are there any key takeaways you’d like to share with our audience?
Dr. Milne: One of the takeaways from this whole conversation is that science is iterative and science changes. When new evidence becomes available, and we’ve seen it accumulate around the world, we as scientists, as a researcher, as somebody committed to great patient care should revisit our positions on this. Since there is a prohibition against this medication, I think it’s time to reassess that stance and move forward to see if it still is accurate today.
Dr. Motov: I wholeheartedly agree with this. Thank you, Ken, for bringing this up. Good point.
Dr. Glatter: This has been a really informative discussion. I think our audience will certainly embrace this. Thank you very much for your time; it’s much appreciated.
Dr. Glatter is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical adviser for Medscape and hosts the Hot Topics in EM series. Dr. Milne is an emergency physician at Strathroy Middlesex General Hospital in Ontario, Canada, and the founder of the well-known podcast The Skeptics’ Guide to Emergency Medicine (SGEM). Dr. Motov is professor of emergency medicine and director of research in the Department of Emergency Medicine at Maimonides Medical Center in Brooklyn, New York. He is passionate about safe and effective pain management in the emergency department, and has numerous publications on the subject of opioid alternatives in pain management. Dr. Glatter, Dr. Milne, and Dr. Motov had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
This discussion was recorded on March 29, 2024. The transcript has been edited for clarity.
Robert D. Glatter, MD: Joining me today to discuss the use of methoxyflurane (Penthrox), an inhaled nonopioid analgesic for the relief of acute pain, is Dr. William Kenneth (Ken) Milne, an emergency physician at Strathroy Middlesex General Hospital in Ontario, Canada, and the founder of the well-known podcast The Skeptics’ Guide to Emergency Medicine (SGEM).
Also joining me is Dr. Sergey Motov, an emergency physician and research director at Maimonides Medical Center in Brooklyn, New York, and an expert in pain management. I want to welcome both of you and thank you for joining me.
RAMPED Trial: Evaluating the Efficacy of Methoxyflurane
Dr. Glatter: Ken, your recent post on Twitter [now X] regarding the utility of Penthrox in the RAMPED trial really caught my attention. While the trial was from 2021, it really is relevant regarding the prehospital management of pain in the practice of emergency medicine, and certainly in-hospital practice. I was hoping you could review the study design but also get into the rationale behind the use of this novel agent.
William Kenneth (Ken) Milne, MD, MSc: Sure. I’d be happy to kick this episode off with talking about a study that was published in 2020 in Academic Emergency Medicine. It was an Australian study by Brichko et al., and they were doing a randomized controlled trial looking at methoxyflurane vs standard care.
They selected out a population of adults, which they defined as 18-75 years of age. They were in the prehospital setting and they had a pain score of greater than 8. They gave the participants methoxyflurane, which is also called the “green whistle.” They had the subjects take that for their prehospital pain, and they compared that with whatever your standard analgesic in the prehospital setting would be.
Their primary outcome was how many patients had at least 50% reduction in their pain score within 30 minutes. They recruited about 120 people, and they found that there was no statistical difference in the primary outcome between methoxyflurane and standard care. Again, that primary outcome was a reduction in pain score by greater than 50% at 30 minutes, and there wasn’t a statistical difference between the two.
There are obviously limits to any study, and it was a convenience sample. This was an unmasked trial, so people knew if they were getting this green whistle, which is popular in Australia. People would be familiar with this device, and they didn’t compare it with a sham or placebo group.
Pharmacology of Penthrox: Its Role and Mechanism of Action
Dr. Glatter: The primary outcome wasn’t met, but certainly secondary outcomes were. There was, again, a relatively small number of patients in this trial. That said, there was significant pain relief. I think there are issues with the trial, as with any trial limitations.
Getting to the pharmacology of Penthrox, can you describe this inhaled anesthetic and how we use it, specifically its role at the subanesthetic doses?
Sergey M. Motov, MD: Methoxyflurane is embedded in the green whistle package, and that whole contraption is called Penthrox. It’s an inhaled volatile fluorinated hydrocarbon anesthetic that was predominantly used, I’d say 40, 50 years ago, for general anesthesia and slowly but surely fell out of favor due to the fact that, when used for prolonged duration or in supratherapeutic doses, there were cases of severe or even fatal nephrotoxicity and hepatotoxicity.
In the late ‘70s and early ‘80s, all the fluranes came on board that are slightly different as general anesthetics, and methoxyflurane started slowly falling out of favor. Because of this paucity and then a subsequent slightly greater number of cases of nephrotoxicity and hepatotoxicity, [the US Food and Drug Administration] FDA made a decision to pull the drug off the market in 2005. FDA successfully accomplished its mission and since then has pretty much banned the use of inhaled methoxyflurane in any shape, form, or color in the United States.
Going back to the green whistle, it has been used in Australia probably for about 50-60 years, and has been used in Europe for probably 10-20 years. Ken can attest that it has been used in Canada for at least a decade and the track record is phenomenal.
We are using subanesthetic, even supratherapeutic doses that, based on available literature, has no incidence of this fatal hepatotoxicity or nephrotoxicity. We’re talking about 10 million doses administered worldwide, except in the United States. There are 40-plus randomized clinical trials with over 30,000 patients enrolled that prove efficacy and safety.
That’s where we are right now, in a conundrum. We have a great deal of data all over the world, except in the United States, that push for the use of this noninvasive, patient-controlled nonopioid inhaled anesthetic. We just don’t have the access in North America, with the exception of Canada.
Regulatory Hurdles: Challenges in FDA Approval
Dr. Glatter: Absolutely. The FDA wants to be cautious, but if you look at the evidence base of data on this, it really indicates otherwise. Do you think that these roadblocks can be somehow overcome?
Dr. Milne: In the 2000s and 2010s, everybody was focused on opioids and all the dangers and potential adverse events. Opioids are great drugs like many other drugs; it depends on dose and duration. If used properly, it’s an excellent drug. Well, here’s another excellent drug if it’s used properly, and the adverse events are dependent on their dose and duration. Penthrox, or methoxyflurane, is a subtherapeutic, small dose and there have been no reported cases of addiction or abuse related to these inhalers.
Dr. Glatter: That argues for the point — and I’ll turn this over to you, Sergey — of how can this not, in my mind, be an issue that the FDA can overcome.
Dr. Motov: I agree with you. It’s very hard for me to speak on behalf of the FDA, to allude to their thinking processes, but we need to be up to speed with the evidence. The first thing is, why don’t you study the drug in the United States? I’m not asking you to lift the ban, which you put in 2005, but why don’t you honor what has been done over two decades and at least open the door a little bit and let us do what we do best? Why don’t you allow us to do the research in a controlled setting with a carefully, properly selected group of patients without underlying renal or hepatic insufficiency and see where we’re at?
Let’s compare it against placebo. If that’s not ethical, let’s compare it against active comparators — God knows we have 15-20 drugs we can use — and let’s see where we’re at. Ken has been nothing short of superb when it comes to evidence. Let us put the evidence together.
Dr. Milne: If there were concerns decades ago, those need to be addressed. As science is iterative and as other information becomes available, the scientific method would say, Let’s reexamine this and let’s reexamine our position, and do that with evidence. To do that, it has to have validity within the US system. Someone like you doing the research, you are a pain research guru; you should be doing this research to say, “Does it work or not? Does this nonapproval still stand today in 2024?”
Dr. Motov: Thank you for the shout-out, and I agree with you. All of us, those who are interested, on the frontiers of emergency care — as present clinicians — we should be doing this. There is nothing that will convince the FDA more than properly and rightly conducted research, time to reassess the evidence, and time to be less rigid. I understand that you placed a ban 20 years ago, but let’s go with the science. We cannot be behind it.
Exploring the Ecological Footprint of Methoxyflurane
Dr. Milne: There was an Austrian study in 2022 and a very interesting study out of the UK looking at life-cycle impact assessment on the environment. If we’re not just concerned about patient care —obviously, we want to provide patients with a safe and effective product, compared with other products that are available that might not have as good a safety profile — this looks at the impact on the environment.
Dr. Glatter: Ken, can you tell me about some of your recent research regarding the environmental effects related to use of Penthrox, but also its utility pharmacologically and its mechanism of action?
Dr. Milne: There was a really interesting study published this year by Martindale in the Emergency Medicine Journal. It took a different approach to this question about could we be using this drug, and why should we be using this drug? Sergey and I have already talked about the potential benefits and the potential harms. I mentioned opioids and some of the concerns about that. For this drug, if we’re using it in the prehospital setting in this little green whistle, the potential benefits look really good, and we haven’t seen any of the potential harms come through in the literature.
This was another line of evidence of why this might be a good drug, because of the environmental impact of this low-dose methoxyflurane. They compared it with nitrous oxide and said, “Well, what about the life-cycle impact on the environment of using this and the overall cradle-to-grave environmental impacts?”
Obviously, Sergey and I are interested in patient care, and we treat patients one at a time. But we have a larger responsibility to social determinants of health, like our environment. If you look at the overall cradle-to-grave environmental impact of this drug, it was better than for nitrous oxide when looking specifically at climate-change impact. That might be another reason, another line of argument, that could be put forward in the United States to say, “We want to have a healthy environment and a healthy option for patients.”
I’ll let Sergey speak to mechanisms of action and those types of things.
Dr. Motov: As a general anesthetic and hydrocarbonated volatile ones, I’m just going to say that it causes this generalized diffuse cortical depression, and there are no particular channels, receptors, or enzymes we need to worry much about. In short, it’s an inhaled gas used to put patients or people to sleep.
Over the past 30 or 40 years — and I’ll go back to the past decade — there have been numerous studies in different countries (outside of the United States, of course), and with the recent study that Ken just cited, there were comparisons for managing predominantly acute traumatic injuries in pediatric and adult populations presenting to EDs in various regions of the world that compared Penthrox, or the green whistle, with either placebo or active comparators, which included parenteral opioids, oral opioids, and NSAIDs.
The recent systematic review by Fabbri, out of Italy, showed that for ultra–short-term pain — we’re talking about 5, 10, or 15 minutes — inhaled methoxyflurane was found to be equal or even superior to standard of care, primarily related to parenteral opioids, and safety was off the hook. Interestingly, with respect to analgesia, they found that geriatric patients seemed to be responding more, with respect to changing pain score, than younger adults — we’re talking about ages 18-64 vs 65 or older. Again, we need to make sure that we carefully select those elderly people without underlying renal or hepatic insufficiency.
To wrap this up, there is evidence clearly supporting its analgesic efficacy and safety, even in comparison to commonly used and traditionally accepted analgesic modalities that we use for managing acute pain.
US Military Use and Implications for Civilian Practice
Dr. Glatter: Do you think that methoxyflurane’s use in the military will help propel its use in clinical settings in the US, and possibly convince the FDA to look at this closer? The military is currently using it in deployed combat veterans in an ongoing fashion.
Dr. Motov: I’m excited that the Department of Defense in the United States has taken the lead, and they’re being very progressive. There are data that we’ve adapted to the civilian environment by use of intranasal opioids and intranasal ketamine with more doctors who came out of the military. In the military, it’s a kingdom within a kingdom. I don’t know their relationship with the FDA, but I support the military’s pharmacologic initiative by honoring and disseminating their research once it becomes available.
For us nonmilitary folks, we still need to work with the FDA. We need to convince the FDA to let us study the drug, and then we need to pile the evidence within the United States so that the FDA will start looking at this favorably. It wouldn’t hurt and it wouldn’t harm. Any piece of evidence will add to the existing body of literature that we need to allow this medication to be available to us.
Safety Considerations and Aerosolization Concerns
Dr. Glatter: Its safety in children is well established in Australia and throughout the world. I think it deserves a careful look, and the evidence that you’ve both presented argues for the use of this prehospital but also in hospital. I guess there was concern in the hospital with underventilation and healthcare workers being exposed to the fumes, and then getting headaches, dizziness, and so forth. I don’t know if that’s borne out, Ken, in any of your experience in Canada at all.
Dr. Milne: We currently don’t have it in our shop. It’s being used in British Columbia right now in the prehospital setting, and I’m not aware of anybody using it in their department. It’s used prehospital as far as I know.
Dr. Motov: I can attest to it, if I may, because I had familiarized myself with the device. I actually was able to hold it in my hands. I have not used it yet but I had the prototype. The way it’s set up, there is an activated charcoal chamber that sits right on top of the device, which serves as the scavenger for exhaled air that contains particles of methoxyflurane. In theory, but I’m telling how it is in practicality, it significantly reduces occupational exposure, based on data that lacks specifics.
Although most of the researchers did not measure the concentration of methoxyflurane in ambient air within the treatment room in the EDs, I believe the additional data sources clearly stating that it’s within or even below the detectable level that would cause any harm. Once again, we need to honor pathology. We need to make sure that pregnant women will not be exposed to it.
Dr. Milne: In 2024, we also need to be concerned about aerosolizing procedures and aerosolizing treatments, and just take that into account because we should be considering all the potential benefits and all the potential harms. Going through the COVID-19 pandemic, there was concern about transmission and whether or not it was droplet or aerosolized.
There was an observational study published in 2022 in Austria by Trimmel in BMC Emergency Medicine showing similar results. It seemed to work well and potential harms didn’t get picked up. They had to stop the study early because of COVID-19.
We need to always focus in on the potential benefits, the potential harms; where does the science land? Where do the data lie? Then we move forward from that and make informed decisions.
Final Thoughts
Dr. Glatter: Are there any key takeaways you’d like to share with our audience?
Dr. Milne: One of the takeaways from this whole conversation is that science is iterative and science changes. When new evidence becomes available, and we’ve seen it accumulate around the world, we as scientists, as a researcher, as somebody committed to great patient care should revisit our positions on this. Since there is a prohibition against this medication, I think it’s time to reassess that stance and move forward to see if it still is accurate today.
Dr. Motov: I wholeheartedly agree with this. Thank you, Ken, for bringing this up. Good point.
Dr. Glatter: This has been a really informative discussion. I think our audience will certainly embrace this. Thank you very much for your time; it’s much appreciated.
Dr. Glatter is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical adviser for Medscape and hosts the Hot Topics in EM series. Dr. Milne is an emergency physician at Strathroy Middlesex General Hospital in Ontario, Canada, and the founder of the well-known podcast The Skeptics’ Guide to Emergency Medicine (SGEM). Dr. Motov is professor of emergency medicine and director of research in the Department of Emergency Medicine at Maimonides Medical Center in Brooklyn, New York. He is passionate about safe and effective pain management in the emergency department, and has numerous publications on the subject of opioid alternatives in pain management. Dr. Glatter, Dr. Milne, and Dr. Motov had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
This discussion was recorded on March 29, 2024. The transcript has been edited for clarity.
Robert D. Glatter, MD: Joining me today to discuss the use of methoxyflurane (Penthrox), an inhaled nonopioid analgesic for the relief of acute pain, is Dr. William Kenneth (Ken) Milne, an emergency physician at Strathroy Middlesex General Hospital in Ontario, Canada, and the founder of the well-known podcast The Skeptics’ Guide to Emergency Medicine (SGEM).
Also joining me is Dr. Sergey Motov, an emergency physician and research director at Maimonides Medical Center in Brooklyn, New York, and an expert in pain management. I want to welcome both of you and thank you for joining me.
RAMPED Trial: Evaluating the Efficacy of Methoxyflurane
Dr. Glatter: Ken, your recent post on Twitter [now X] regarding the utility of Penthrox in the RAMPED trial really caught my attention. While the trial was from 2021, it really is relevant regarding the prehospital management of pain in the practice of emergency medicine, and certainly in-hospital practice. I was hoping you could review the study design but also get into the rationale behind the use of this novel agent.
William Kenneth (Ken) Milne, MD, MSc: Sure. I’d be happy to kick this episode off with talking about a study that was published in 2020 in Academic Emergency Medicine. It was an Australian study by Brichko et al., and they were doing a randomized controlled trial looking at methoxyflurane vs standard care.
They selected out a population of adults, which they defined as 18-75 years of age. They were in the prehospital setting and they had a pain score of greater than 8. They gave the participants methoxyflurane, which is also called the “green whistle.” They had the subjects take that for their prehospital pain, and they compared that with whatever your standard analgesic in the prehospital setting would be.
Their primary outcome was how many patients had at least 50% reduction in their pain score within 30 minutes. They recruited about 120 people, and they found that there was no statistical difference in the primary outcome between methoxyflurane and standard care. Again, that primary outcome was a reduction in pain score by greater than 50% at 30 minutes, and there wasn’t a statistical difference between the two.
There are obviously limits to any study, and it was a convenience sample. This was an unmasked trial, so people knew if they were getting this green whistle, which is popular in Australia. People would be familiar with this device, and they didn’t compare it with a sham or placebo group.
Pharmacology of Penthrox: Its Role and Mechanism of Action
Dr. Glatter: The primary outcome wasn’t met, but certainly secondary outcomes were. There was, again, a relatively small number of patients in this trial. That said, there was significant pain relief. I think there are issues with the trial, as with any trial limitations.
Getting to the pharmacology of Penthrox, can you describe this inhaled anesthetic and how we use it, specifically its role at the subanesthetic doses?
Sergey M. Motov, MD: Methoxyflurane is embedded in the green whistle package, and that whole contraption is called Penthrox. It’s an inhaled volatile fluorinated hydrocarbon anesthetic that was predominantly used, I’d say 40, 50 years ago, for general anesthesia and slowly but surely fell out of favor due to the fact that, when used for prolonged duration or in supratherapeutic doses, there were cases of severe or even fatal nephrotoxicity and hepatotoxicity.
In the late ‘70s and early ‘80s, all the fluranes came on board that are slightly different as general anesthetics, and methoxyflurane started slowly falling out of favor. Because of this paucity and then a subsequent slightly greater number of cases of nephrotoxicity and hepatotoxicity, [the US Food and Drug Administration] FDA made a decision to pull the drug off the market in 2005. FDA successfully accomplished its mission and since then has pretty much banned the use of inhaled methoxyflurane in any shape, form, or color in the United States.
Going back to the green whistle, it has been used in Australia probably for about 50-60 years, and has been used in Europe for probably 10-20 years. Ken can attest that it has been used in Canada for at least a decade and the track record is phenomenal.
We are using subanesthetic, even supratherapeutic doses that, based on available literature, has no incidence of this fatal hepatotoxicity or nephrotoxicity. We’re talking about 10 million doses administered worldwide, except in the United States. There are 40-plus randomized clinical trials with over 30,000 patients enrolled that prove efficacy and safety.
That’s where we are right now, in a conundrum. We have a great deal of data all over the world, except in the United States, that push for the use of this noninvasive, patient-controlled nonopioid inhaled anesthetic. We just don’t have the access in North America, with the exception of Canada.
Regulatory Hurdles: Challenges in FDA Approval
Dr. Glatter: Absolutely. The FDA wants to be cautious, but if you look at the evidence base of data on this, it really indicates otherwise. Do you think that these roadblocks can be somehow overcome?
Dr. Milne: In the 2000s and 2010s, everybody was focused on opioids and all the dangers and potential adverse events. Opioids are great drugs like many other drugs; it depends on dose and duration. If used properly, it’s an excellent drug. Well, here’s another excellent drug if it’s used properly, and the adverse events are dependent on their dose and duration. Penthrox, or methoxyflurane, is a subtherapeutic, small dose and there have been no reported cases of addiction or abuse related to these inhalers.
Dr. Glatter: That argues for the point — and I’ll turn this over to you, Sergey — of how can this not, in my mind, be an issue that the FDA can overcome.
Dr. Motov: I agree with you. It’s very hard for me to speak on behalf of the FDA, to allude to their thinking processes, but we need to be up to speed with the evidence. The first thing is, why don’t you study the drug in the United States? I’m not asking you to lift the ban, which you put in 2005, but why don’t you honor what has been done over two decades and at least open the door a little bit and let us do what we do best? Why don’t you allow us to do the research in a controlled setting with a carefully, properly selected group of patients without underlying renal or hepatic insufficiency and see where we’re at?
Let’s compare it against placebo. If that’s not ethical, let’s compare it against active comparators — God knows we have 15-20 drugs we can use — and let’s see where we’re at. Ken has been nothing short of superb when it comes to evidence. Let us put the evidence together.
Dr. Milne: If there were concerns decades ago, those need to be addressed. As science is iterative and as other information becomes available, the scientific method would say, Let’s reexamine this and let’s reexamine our position, and do that with evidence. To do that, it has to have validity within the US system. Someone like you doing the research, you are a pain research guru; you should be doing this research to say, “Does it work or not? Does this nonapproval still stand today in 2024?”
Dr. Motov: Thank you for the shout-out, and I agree with you. All of us, those who are interested, on the frontiers of emergency care — as present clinicians — we should be doing this. There is nothing that will convince the FDA more than properly and rightly conducted research, time to reassess the evidence, and time to be less rigid. I understand that you placed a ban 20 years ago, but let’s go with the science. We cannot be behind it.
Exploring the Ecological Footprint of Methoxyflurane
Dr. Milne: There was an Austrian study in 2022 and a very interesting study out of the UK looking at life-cycle impact assessment on the environment. If we’re not just concerned about patient care —obviously, we want to provide patients with a safe and effective product, compared with other products that are available that might not have as good a safety profile — this looks at the impact on the environment.
Dr. Glatter: Ken, can you tell me about some of your recent research regarding the environmental effects related to use of Penthrox, but also its utility pharmacologically and its mechanism of action?
Dr. Milne: There was a really interesting study published this year by Martindale in the Emergency Medicine Journal. It took a different approach to this question about could we be using this drug, and why should we be using this drug? Sergey and I have already talked about the potential benefits and the potential harms. I mentioned opioids and some of the concerns about that. For this drug, if we’re using it in the prehospital setting in this little green whistle, the potential benefits look really good, and we haven’t seen any of the potential harms come through in the literature.
This was another line of evidence of why this might be a good drug, because of the environmental impact of this low-dose methoxyflurane. They compared it with nitrous oxide and said, “Well, what about the life-cycle impact on the environment of using this and the overall cradle-to-grave environmental impacts?”
Obviously, Sergey and I are interested in patient care, and we treat patients one at a time. But we have a larger responsibility to social determinants of health, like our environment. If you look at the overall cradle-to-grave environmental impact of this drug, it was better than for nitrous oxide when looking specifically at climate-change impact. That might be another reason, another line of argument, that could be put forward in the United States to say, “We want to have a healthy environment and a healthy option for patients.”
I’ll let Sergey speak to mechanisms of action and those types of things.
Dr. Motov: As a general anesthetic and hydrocarbonated volatile ones, I’m just going to say that it causes this generalized diffuse cortical depression, and there are no particular channels, receptors, or enzymes we need to worry much about. In short, it’s an inhaled gas used to put patients or people to sleep.
Over the past 30 or 40 years — and I’ll go back to the past decade — there have been numerous studies in different countries (outside of the United States, of course), and with the recent study that Ken just cited, there were comparisons for managing predominantly acute traumatic injuries in pediatric and adult populations presenting to EDs in various regions of the world that compared Penthrox, or the green whistle, with either placebo or active comparators, which included parenteral opioids, oral opioids, and NSAIDs.
The recent systematic review by Fabbri, out of Italy, showed that for ultra–short-term pain — we’re talking about 5, 10, or 15 minutes — inhaled methoxyflurane was found to be equal or even superior to standard of care, primarily related to parenteral opioids, and safety was off the hook. Interestingly, with respect to analgesia, they found that geriatric patients seemed to be responding more, with respect to changing pain score, than younger adults — we’re talking about ages 18-64 vs 65 or older. Again, we need to make sure that we carefully select those elderly people without underlying renal or hepatic insufficiency.
To wrap this up, there is evidence clearly supporting its analgesic efficacy and safety, even in comparison to commonly used and traditionally accepted analgesic modalities that we use for managing acute pain.
US Military Use and Implications for Civilian Practice
Dr. Glatter: Do you think that methoxyflurane’s use in the military will help propel its use in clinical settings in the US, and possibly convince the FDA to look at this closer? The military is currently using it in deployed combat veterans in an ongoing fashion.
Dr. Motov: I’m excited that the Department of Defense in the United States has taken the lead, and they’re being very progressive. There are data that we’ve adapted to the civilian environment by use of intranasal opioids and intranasal ketamine with more doctors who came out of the military. In the military, it’s a kingdom within a kingdom. I don’t know their relationship with the FDA, but I support the military’s pharmacologic initiative by honoring and disseminating their research once it becomes available.
For us nonmilitary folks, we still need to work with the FDA. We need to convince the FDA to let us study the drug, and then we need to pile the evidence within the United States so that the FDA will start looking at this favorably. It wouldn’t hurt and it wouldn’t harm. Any piece of evidence will add to the existing body of literature that we need to allow this medication to be available to us.
Safety Considerations and Aerosolization Concerns
Dr. Glatter: Its safety in children is well established in Australia and throughout the world. I think it deserves a careful look, and the evidence that you’ve both presented argues for the use of this prehospital but also in hospital. I guess there was concern in the hospital with underventilation and healthcare workers being exposed to the fumes, and then getting headaches, dizziness, and so forth. I don’t know if that’s borne out, Ken, in any of your experience in Canada at all.
Dr. Milne: We currently don’t have it in our shop. It’s being used in British Columbia right now in the prehospital setting, and I’m not aware of anybody using it in their department. It’s used prehospital as far as I know.
Dr. Motov: I can attest to it, if I may, because I had familiarized myself with the device. I actually was able to hold it in my hands. I have not used it yet but I had the prototype. The way it’s set up, there is an activated charcoal chamber that sits right on top of the device, which serves as the scavenger for exhaled air that contains particles of methoxyflurane. In theory, but I’m telling how it is in practicality, it significantly reduces occupational exposure, based on data that lacks specifics.
Although most of the researchers did not measure the concentration of methoxyflurane in ambient air within the treatment room in the EDs, I believe the additional data sources clearly stating that it’s within or even below the detectable level that would cause any harm. Once again, we need to honor pathology. We need to make sure that pregnant women will not be exposed to it.
Dr. Milne: In 2024, we also need to be concerned about aerosolizing procedures and aerosolizing treatments, and just take that into account because we should be considering all the potential benefits and all the potential harms. Going through the COVID-19 pandemic, there was concern about transmission and whether or not it was droplet or aerosolized.
There was an observational study published in 2022 in Austria by Trimmel in BMC Emergency Medicine showing similar results. It seemed to work well and potential harms didn’t get picked up. They had to stop the study early because of COVID-19.
We need to always focus in on the potential benefits, the potential harms; where does the science land? Where do the data lie? Then we move forward from that and make informed decisions.
Final Thoughts
Dr. Glatter: Are there any key takeaways you’d like to share with our audience?
Dr. Milne: One of the takeaways from this whole conversation is that science is iterative and science changes. When new evidence becomes available, and we’ve seen it accumulate around the world, we as scientists, as a researcher, as somebody committed to great patient care should revisit our positions on this. Since there is a prohibition against this medication, I think it’s time to reassess that stance and move forward to see if it still is accurate today.
Dr. Motov: I wholeheartedly agree with this. Thank you, Ken, for bringing this up. Good point.
Dr. Glatter: This has been a really informative discussion. I think our audience will certainly embrace this. Thank you very much for your time; it’s much appreciated.
Dr. Glatter is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical adviser for Medscape and hosts the Hot Topics in EM series. Dr. Milne is an emergency physician at Strathroy Middlesex General Hospital in Ontario, Canada, and the founder of the well-known podcast The Skeptics’ Guide to Emergency Medicine (SGEM). Dr. Motov is professor of emergency medicine and director of research in the Department of Emergency Medicine at Maimonides Medical Center in Brooklyn, New York. He is passionate about safe and effective pain management in the emergency department, and has numerous publications on the subject of opioid alternatives in pain management. Dr. Glatter, Dr. Milne, and Dr. Motov had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
PCP Compensation, Part 2
In my last column, I began to explore the factors affecting the compensation of primary care providers (PCPs). I described two apparent economic paradoxes. First, while most healthcare systems consider their primary care segments as loss leaders, they continue to seek and hire more PCPs. The second is while PCPs are in short supply, most of them feel that they are underpaid. Supply and demand doesn’t seem to be making them more valuable in the economic sense. The explanations for these nonintuitive observations are first, healthcare systems need the volume of patients stored in the practices of even unprofitable primary care physicians to feed the high-profit specialties in their businesses. Second, there is a limit to how large a gap between revenue and overhead the systems can accept for their primary care practices. Not surprisingly, this means that system administrators must continue to nudge those PCP practices closer toward profitability, usually by demanding higher productivity.
As I did in my last letter, I will continue to lean on a discussion for PCP compensation by a large international management consulting firm I found on the internet. I am not condoning the consultant’s advice, but merely using it as a scaffolding on which to hang the rather squishy topics of time, clinical quality, and patient satisfaction. I only intend to ask questions, and I promise no answers.
First, let me make it clear that I am defining PCPs as providers who are on a performance-based pathway, which is by far the most prevalent model. A fixed-salary arrangement hasn’t made sense to me since I was a 17-year-old lifeguard paid by the hour for sitting by a pool. Had I been paid by the rescue, I would have finished the summer empty handed. A fixed salary provided me a sense of security, but it offered no path for advancement and was boring as hell. The primary care provider I am talking about has an interest in developing relationships with his/her patients, building a practice, and offering some degree of continuity. In other words, I am not considering providers working in walk-in clinics as PCPs.
Size Matters
My high-powered management consultant is recommending to his healthcare system management clients that they emphasize panel size component as they craft their compensation packages for PCPs. Maybe even to the point of giving it more weight than the productivity piece. This, of course, makes perfect business sense if the primary value of a PCP to the system lies in the patients he/she brings into the system.
What does this emphasis on size mean for you as a provider? If your boss is following my consultant’s advice, then you would want to be growing your panel size to improve your compensation. You could do this by a marketing plan that makes you more popular. But, I can hear you muttering that you never wanted to be a contestant in a popularity contest. Although I must say that historically this was a fact of life in any community when new providers came to town.
A provider can choose his/her own definition of popularity. You can let it be known that you are a liberal prescription writer and fill your practice with drug-seeking patients. Or you could promote customer-friendly schedules and behaviors in your office staff. And, of course, you can simply exude an aura of caring, which has always been an effective practice-building tool.
On the other hand, you may believe that you have more patients than you can handle. You may fear that growing your practice runs the risk of putting the quality of your patients’ care and your own physical and mental health at risk.
Theoretically, you could keep your panel size unchanged and increase your productivity to enhance your value and therefore your compensation. In the next part of this miniseries we’ll look at the stumbling blocks that can make increasing productivity difficult.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
In my last column, I began to explore the factors affecting the compensation of primary care providers (PCPs). I described two apparent economic paradoxes. First, while most healthcare systems consider their primary care segments as loss leaders, they continue to seek and hire more PCPs. The second is while PCPs are in short supply, most of them feel that they are underpaid. Supply and demand doesn’t seem to be making them more valuable in the economic sense. The explanations for these nonintuitive observations are first, healthcare systems need the volume of patients stored in the practices of even unprofitable primary care physicians to feed the high-profit specialties in their businesses. Second, there is a limit to how large a gap between revenue and overhead the systems can accept for their primary care practices. Not surprisingly, this means that system administrators must continue to nudge those PCP practices closer toward profitability, usually by demanding higher productivity.
As I did in my last letter, I will continue to lean on a discussion for PCP compensation by a large international management consulting firm I found on the internet. I am not condoning the consultant’s advice, but merely using it as a scaffolding on which to hang the rather squishy topics of time, clinical quality, and patient satisfaction. I only intend to ask questions, and I promise no answers.
First, let me make it clear that I am defining PCPs as providers who are on a performance-based pathway, which is by far the most prevalent model. A fixed-salary arrangement hasn’t made sense to me since I was a 17-year-old lifeguard paid by the hour for sitting by a pool. Had I been paid by the rescue, I would have finished the summer empty handed. A fixed salary provided me a sense of security, but it offered no path for advancement and was boring as hell. The primary care provider I am talking about has an interest in developing relationships with his/her patients, building a practice, and offering some degree of continuity. In other words, I am not considering providers working in walk-in clinics as PCPs.
Size Matters
My high-powered management consultant is recommending to his healthcare system management clients that they emphasize panel size component as they craft their compensation packages for PCPs. Maybe even to the point of giving it more weight than the productivity piece. This, of course, makes perfect business sense if the primary value of a PCP to the system lies in the patients he/she brings into the system.
What does this emphasis on size mean for you as a provider? If your boss is following my consultant’s advice, then you would want to be growing your panel size to improve your compensation. You could do this by a marketing plan that makes you more popular. But, I can hear you muttering that you never wanted to be a contestant in a popularity contest. Although I must say that historically this was a fact of life in any community when new providers came to town.
A provider can choose his/her own definition of popularity. You can let it be known that you are a liberal prescription writer and fill your practice with drug-seeking patients. Or you could promote customer-friendly schedules and behaviors in your office staff. And, of course, you can simply exude an aura of caring, which has always been an effective practice-building tool.
On the other hand, you may believe that you have more patients than you can handle. You may fear that growing your practice runs the risk of putting the quality of your patients’ care and your own physical and mental health at risk.
Theoretically, you could keep your panel size unchanged and increase your productivity to enhance your value and therefore your compensation. In the next part of this miniseries we’ll look at the stumbling blocks that can make increasing productivity difficult.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
In my last column, I began to explore the factors affecting the compensation of primary care providers (PCPs). I described two apparent economic paradoxes. First, while most healthcare systems consider their primary care segments as loss leaders, they continue to seek and hire more PCPs. The second is while PCPs are in short supply, most of them feel that they are underpaid. Supply and demand doesn’t seem to be making them more valuable in the economic sense. The explanations for these nonintuitive observations are first, healthcare systems need the volume of patients stored in the practices of even unprofitable primary care physicians to feed the high-profit specialties in their businesses. Second, there is a limit to how large a gap between revenue and overhead the systems can accept for their primary care practices. Not surprisingly, this means that system administrators must continue to nudge those PCP practices closer toward profitability, usually by demanding higher productivity.
As I did in my last letter, I will continue to lean on a discussion for PCP compensation by a large international management consulting firm I found on the internet. I am not condoning the consultant’s advice, but merely using it as a scaffolding on which to hang the rather squishy topics of time, clinical quality, and patient satisfaction. I only intend to ask questions, and I promise no answers.
First, let me make it clear that I am defining PCPs as providers who are on a performance-based pathway, which is by far the most prevalent model. A fixed-salary arrangement hasn’t made sense to me since I was a 17-year-old lifeguard paid by the hour for sitting by a pool. Had I been paid by the rescue, I would have finished the summer empty handed. A fixed salary provided me a sense of security, but it offered no path for advancement and was boring as hell. The primary care provider I am talking about has an interest in developing relationships with his/her patients, building a practice, and offering some degree of continuity. In other words, I am not considering providers working in walk-in clinics as PCPs.
Size Matters
My high-powered management consultant is recommending to his healthcare system management clients that they emphasize panel size component as they craft their compensation packages for PCPs. Maybe even to the point of giving it more weight than the productivity piece. This, of course, makes perfect business sense if the primary value of a PCP to the system lies in the patients he/she brings into the system.
What does this emphasis on size mean for you as a provider? If your boss is following my consultant’s advice, then you would want to be growing your panel size to improve your compensation. You could do this by a marketing plan that makes you more popular. But, I can hear you muttering that you never wanted to be a contestant in a popularity contest. Although I must say that historically this was a fact of life in any community when new providers came to town.
A provider can choose his/her own definition of popularity. You can let it be known that you are a liberal prescription writer and fill your practice with drug-seeking patients. Or you could promote customer-friendly schedules and behaviors in your office staff. And, of course, you can simply exude an aura of caring, which has always been an effective practice-building tool.
On the other hand, you may believe that you have more patients than you can handle. You may fear that growing your practice runs the risk of putting the quality of your patients’ care and your own physical and mental health at risk.
Theoretically, you could keep your panel size unchanged and increase your productivity to enhance your value and therefore your compensation. In the next part of this miniseries we’ll look at the stumbling blocks that can make increasing productivity difficult.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Big Pharma, Small Payments
A recent review of the Open Payments database found that, over the last 10 years, the evil forces of Big Pharma have paid doctors $12.1 billion dollars.
That’s a lot.
Of course, there are also quite a few doctors out there, and the word “paid” is kind of a misnomer. Yes, some people did get paid directly — cash for research, speaking engagements, teaching other docs — but a lot of the money was really spent on marketing. It may show that Dr. Jones was “paid” $200 one day, when in reality that was the cost of providing lunch to her, her five-person office staff, and the medical student following her around that afternoon.
In the last 10 years, I’ve accepted “payments” of one pizza and three iced coffees, so I guess I’m on there, too.
When you actually break it down, this comes out to a national average of (drum roll) $48 per doctor over 10 years.
Let’s face it, if your prescribing habits can be bought for $4.80 a year ... that’s pretty sad. They say everyone has their price, but hopefully it’s not that of a Happy Meal.
I understand the reasons for tracking this sort of thing. The system certainly can be — and has been — gamed for abuse. If one doctor is getting a ridiculous amount of money for doing nothing but writing scripts for Walletgouge-XR, that certainly needs to be known. Something is rotten in the state of Denmark (or wherever).
But the headline, especially when used in the lay media, makes it sound like all docs are on payola, and further erodes trust in the medical field. The fact that it works out to $4.80 per doctor each year is going to buried deeper in the article, by which time most readers will have moved on to see what Taylor Swift is up to.
Perhaps I’ve taken it to an extreme, but since the pizza (2014) I haven’t done lunch at my office. I still meet with reps, but they’re told now that I don’t do lunch, or bagels, or even iced coffee anymore. Tell me what I need to know about the new drug, but at this point in my career I’d rather have time. By not meeting a rep over lunch, or coffee, it adds 30-60 minutes to my day to use for reviewing tests, returning calls, and typing up notes. Those are things I’m going to have to do at some point, so I’d rather do them at my office and have the extra time at home, even if it’s just to do a jigsaw puzzle with my daughter.
That’s worth more than $4.80 per year.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
A recent review of the Open Payments database found that, over the last 10 years, the evil forces of Big Pharma have paid doctors $12.1 billion dollars.
That’s a lot.
Of course, there are also quite a few doctors out there, and the word “paid” is kind of a misnomer. Yes, some people did get paid directly — cash for research, speaking engagements, teaching other docs — but a lot of the money was really spent on marketing. It may show that Dr. Jones was “paid” $200 one day, when in reality that was the cost of providing lunch to her, her five-person office staff, and the medical student following her around that afternoon.
In the last 10 years, I’ve accepted “payments” of one pizza and three iced coffees, so I guess I’m on there, too.
When you actually break it down, this comes out to a national average of (drum roll) $48 per doctor over 10 years.
Let’s face it, if your prescribing habits can be bought for $4.80 a year ... that’s pretty sad. They say everyone has their price, but hopefully it’s not that of a Happy Meal.
I understand the reasons for tracking this sort of thing. The system certainly can be — and has been — gamed for abuse. If one doctor is getting a ridiculous amount of money for doing nothing but writing scripts for Walletgouge-XR, that certainly needs to be known. Something is rotten in the state of Denmark (or wherever).
But the headline, especially when used in the lay media, makes it sound like all docs are on payola, and further erodes trust in the medical field. The fact that it works out to $4.80 per doctor each year is going to buried deeper in the article, by which time most readers will have moved on to see what Taylor Swift is up to.
Perhaps I’ve taken it to an extreme, but since the pizza (2014) I haven’t done lunch at my office. I still meet with reps, but they’re told now that I don’t do lunch, or bagels, or even iced coffee anymore. Tell me what I need to know about the new drug, but at this point in my career I’d rather have time. By not meeting a rep over lunch, or coffee, it adds 30-60 minutes to my day to use for reviewing tests, returning calls, and typing up notes. Those are things I’m going to have to do at some point, so I’d rather do them at my office and have the extra time at home, even if it’s just to do a jigsaw puzzle with my daughter.
That’s worth more than $4.80 per year.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
A recent review of the Open Payments database found that, over the last 10 years, the evil forces of Big Pharma have paid doctors $12.1 billion dollars.
That’s a lot.
Of course, there are also quite a few doctors out there, and the word “paid” is kind of a misnomer. Yes, some people did get paid directly — cash for research, speaking engagements, teaching other docs — but a lot of the money was really spent on marketing. It may show that Dr. Jones was “paid” $200 one day, when in reality that was the cost of providing lunch to her, her five-person office staff, and the medical student following her around that afternoon.
In the last 10 years, I’ve accepted “payments” of one pizza and three iced coffees, so I guess I’m on there, too.
When you actually break it down, this comes out to a national average of (drum roll) $48 per doctor over 10 years.
Let’s face it, if your prescribing habits can be bought for $4.80 a year ... that’s pretty sad. They say everyone has their price, but hopefully it’s not that of a Happy Meal.
I understand the reasons for tracking this sort of thing. The system certainly can be — and has been — gamed for abuse. If one doctor is getting a ridiculous amount of money for doing nothing but writing scripts for Walletgouge-XR, that certainly needs to be known. Something is rotten in the state of Denmark (or wherever).
But the headline, especially when used in the lay media, makes it sound like all docs are on payola, and further erodes trust in the medical field. The fact that it works out to $4.80 per doctor each year is going to buried deeper in the article, by which time most readers will have moved on to see what Taylor Swift is up to.
Perhaps I’ve taken it to an extreme, but since the pizza (2014) I haven’t done lunch at my office. I still meet with reps, but they’re told now that I don’t do lunch, or bagels, or even iced coffee anymore. Tell me what I need to know about the new drug, but at this point in my career I’d rather have time. By not meeting a rep over lunch, or coffee, it adds 30-60 minutes to my day to use for reviewing tests, returning calls, and typing up notes. Those are things I’m going to have to do at some point, so I’d rather do them at my office and have the extra time at home, even if it’s just to do a jigsaw puzzle with my daughter.
That’s worth more than $4.80 per year.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Intermittent Fasting + HIIT: Fitness Fad or Fix?
Let’s be honest: Although as physicians we have the power of the prescription pad, so much of health, in the end, comes down to lifestyle. Of course, taking a pill is often way easier than changing your longstanding habits. And what’s worse, doesn’t it always seem like the lifestyle stuff that is good for your health is unpleasant?
Two recent lifestyle interventions that I have tried and find really not enjoyable are time-restricted eating (also known as intermittent fasting) and high-intensity interval training, or HIIT. The former leaves me hangry for half the day; the latter is, well, it’s just really hard compared with my usual jog.
But given the rule of unpleasant lifestyle changes, I knew as soon as I saw this recent study what the result would be. What if we combined time-restricted eating with high-intensity interval training?
I’m referring to this study, appearing in PLOS ONE from Ranya Ameur and colleagues, which is a small trial that enrolled otherwise healthy women with a BMI > 30 and randomized them to one of three conditions.
First was time-restricted eating. Women in this group could eat whatever they wanted, but only from 8 a.m. to 4 p.m. daily.
Second: high-intensity functional training. This is a variant of high-intensity interval training which focuses a bit more on resistance exercise than on pure cardiovascular stuff but has the same vibe of doing brief bursts of intensive activity followed by a cool-down period.
Third: a combination of the two. Sounds rough to me.
The study was otherwise straightforward. At baseline, researchers collected data on body composition and dietary intake, and measured blood pressure, glucose, insulin, and lipid biomarkers. A 12-week intervention period followed, after which all of this stuff was measured again.
Now, you may have noticed that there is no control group in this study. We’ll come back to that — a few times.
Let me walk you through some of the outcomes here.
First off, body composition metrics. All three groups lost weight — on average, around 10% of body weight which, for a 12-week intervention, is fairly impressive. BMI and waist circumference went down as well, and, interestingly, much of the weight loss here was in fat mass, not fat-free mass.
Most interventions that lead to weight loss — and I’m including some of the newer drugs here — lead to both fat and muscle loss. That might not be as bad as it sounds; the truth is that muscle mass increases as fat increases because of the simple fact that if you’re carrying more weight when you walk around, your leg muscles get bigger. But to preserve muscle mass in the face of fat loss is sort of a Goldilocks finding, and, based on these results, there’s a suggestion that the high-intensity functional training helps to do just that.
The dietary intake findings were really surprising to me. Across the board, caloric intake decreased. It’s no surprise that time-restricted eating reduces calorie intake. That has been shown many times before and is probably the main reason it induces weight loss — less time to eat means you eat less.
But why would high-intensity functional training lead to lower caloric intake? Most people, myself included, get hungry after they exercise. In fact, one of the reasons it’s hard to lose weight with exercise alone is that we end up eating more calories to make up for what we lost during the exercise. This calorie reduction could be a unique effect of this type of exercise, but honestly this could also be something called the Hawthorne effect. Women in the study kept a food diary to track their intake, and the act of doing that might actually make you eat less. It makes it a little more annoying to snack a bit if you know you have to write it down. This is a situation where I would kill for a control group.
The lipid findings are also pretty striking, with around a 40% reduction in LDL across the board, and evidence of synergistic effects of combined TRE and high-intensity training on total cholesterol and triglycerides. This is like a statin level of effect — pretty impressive. Again, my heart pines for a control group, though.
Same story with glucose and insulin measures: an impressive reduction in fasting glucose and good evidence that the combination of time-restricted eating and high-intensity functional training reduces insulin levels and HOMA-IR as well.
Really the only thing that wasn’t very impressive was the change in blood pressure, with only modest decreases across the board.
Okay, so let’s take a breath after this high-intensity cerebral workout and put this all together. This was a small study, lacking a control group, but with large effect sizes in very relevant clinical areas. It confirms what we know about time-restricted eating — that it makes you eat less calories — and introduces the potential that vigorous exercise can not only magnify the benefits of time-restricted eating but maybe even mitigate some of the risks, like the risk for muscle loss. And of course, it comports with my central hypothesis, which is that the more unpleasant a lifestyle intervention is, the better it is for you. No pain, no gain, right?
Of course, I am being overly dogmatic. There are plenty of caveats. Wrestling bears is quite unpleasant and almost certainly bad for you. And there are even some pleasant things that are pretty good for you — like coffee and sex. And there are even people who find time-restricted eating and high-intensity training pleasurable. They are called masochists.
I’m joking. The truth is that Or, at least, much less painful. The trick is getting over the hump of change. If only there were a pill for that.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships. This transcript has been edited for clarity.
A version of this article appeared on Medscape.com.
Let’s be honest: Although as physicians we have the power of the prescription pad, so much of health, in the end, comes down to lifestyle. Of course, taking a pill is often way easier than changing your longstanding habits. And what’s worse, doesn’t it always seem like the lifestyle stuff that is good for your health is unpleasant?
Two recent lifestyle interventions that I have tried and find really not enjoyable are time-restricted eating (also known as intermittent fasting) and high-intensity interval training, or HIIT. The former leaves me hangry for half the day; the latter is, well, it’s just really hard compared with my usual jog.
But given the rule of unpleasant lifestyle changes, I knew as soon as I saw this recent study what the result would be. What if we combined time-restricted eating with high-intensity interval training?
I’m referring to this study, appearing in PLOS ONE from Ranya Ameur and colleagues, which is a small trial that enrolled otherwise healthy women with a BMI > 30 and randomized them to one of three conditions.
First was time-restricted eating. Women in this group could eat whatever they wanted, but only from 8 a.m. to 4 p.m. daily.
Second: high-intensity functional training. This is a variant of high-intensity interval training which focuses a bit more on resistance exercise than on pure cardiovascular stuff but has the same vibe of doing brief bursts of intensive activity followed by a cool-down period.
Third: a combination of the two. Sounds rough to me.
The study was otherwise straightforward. At baseline, researchers collected data on body composition and dietary intake, and measured blood pressure, glucose, insulin, and lipid biomarkers. A 12-week intervention period followed, after which all of this stuff was measured again.
Now, you may have noticed that there is no control group in this study. We’ll come back to that — a few times.
Let me walk you through some of the outcomes here.
First off, body composition metrics. All three groups lost weight — on average, around 10% of body weight which, for a 12-week intervention, is fairly impressive. BMI and waist circumference went down as well, and, interestingly, much of the weight loss here was in fat mass, not fat-free mass.
Most interventions that lead to weight loss — and I’m including some of the newer drugs here — lead to both fat and muscle loss. That might not be as bad as it sounds; the truth is that muscle mass increases as fat increases because of the simple fact that if you’re carrying more weight when you walk around, your leg muscles get bigger. But to preserve muscle mass in the face of fat loss is sort of a Goldilocks finding, and, based on these results, there’s a suggestion that the high-intensity functional training helps to do just that.
The dietary intake findings were really surprising to me. Across the board, caloric intake decreased. It’s no surprise that time-restricted eating reduces calorie intake. That has been shown many times before and is probably the main reason it induces weight loss — less time to eat means you eat less.
But why would high-intensity functional training lead to lower caloric intake? Most people, myself included, get hungry after they exercise. In fact, one of the reasons it’s hard to lose weight with exercise alone is that we end up eating more calories to make up for what we lost during the exercise. This calorie reduction could be a unique effect of this type of exercise, but honestly this could also be something called the Hawthorne effect. Women in the study kept a food diary to track their intake, and the act of doing that might actually make you eat less. It makes it a little more annoying to snack a bit if you know you have to write it down. This is a situation where I would kill for a control group.
The lipid findings are also pretty striking, with around a 40% reduction in LDL across the board, and evidence of synergistic effects of combined TRE and high-intensity training on total cholesterol and triglycerides. This is like a statin level of effect — pretty impressive. Again, my heart pines for a control group, though.
Same story with glucose and insulin measures: an impressive reduction in fasting glucose and good evidence that the combination of time-restricted eating and high-intensity functional training reduces insulin levels and HOMA-IR as well.
Really the only thing that wasn’t very impressive was the change in blood pressure, with only modest decreases across the board.
Okay, so let’s take a breath after this high-intensity cerebral workout and put this all together. This was a small study, lacking a control group, but with large effect sizes in very relevant clinical areas. It confirms what we know about time-restricted eating — that it makes you eat less calories — and introduces the potential that vigorous exercise can not only magnify the benefits of time-restricted eating but maybe even mitigate some of the risks, like the risk for muscle loss. And of course, it comports with my central hypothesis, which is that the more unpleasant a lifestyle intervention is, the better it is for you. No pain, no gain, right?
Of course, I am being overly dogmatic. There are plenty of caveats. Wrestling bears is quite unpleasant and almost certainly bad for you. And there are even some pleasant things that are pretty good for you — like coffee and sex. And there are even people who find time-restricted eating and high-intensity training pleasurable. They are called masochists.
I’m joking. The truth is that Or, at least, much less painful. The trick is getting over the hump of change. If only there were a pill for that.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships. This transcript has been edited for clarity.
A version of this article appeared on Medscape.com.
Let’s be honest: Although as physicians we have the power of the prescription pad, so much of health, in the end, comes down to lifestyle. Of course, taking a pill is often way easier than changing your longstanding habits. And what’s worse, doesn’t it always seem like the lifestyle stuff that is good for your health is unpleasant?
Two recent lifestyle interventions that I have tried and find really not enjoyable are time-restricted eating (also known as intermittent fasting) and high-intensity interval training, or HIIT. The former leaves me hangry for half the day; the latter is, well, it’s just really hard compared with my usual jog.
But given the rule of unpleasant lifestyle changes, I knew as soon as I saw this recent study what the result would be. What if we combined time-restricted eating with high-intensity interval training?
I’m referring to this study, appearing in PLOS ONE from Ranya Ameur and colleagues, which is a small trial that enrolled otherwise healthy women with a BMI > 30 and randomized them to one of three conditions.
First was time-restricted eating. Women in this group could eat whatever they wanted, but only from 8 a.m. to 4 p.m. daily.
Second: high-intensity functional training. This is a variant of high-intensity interval training which focuses a bit more on resistance exercise than on pure cardiovascular stuff but has the same vibe of doing brief bursts of intensive activity followed by a cool-down period.
Third: a combination of the two. Sounds rough to me.
The study was otherwise straightforward. At baseline, researchers collected data on body composition and dietary intake, and measured blood pressure, glucose, insulin, and lipid biomarkers. A 12-week intervention period followed, after which all of this stuff was measured again.
Now, you may have noticed that there is no control group in this study. We’ll come back to that — a few times.
Let me walk you through some of the outcomes here.
First off, body composition metrics. All three groups lost weight — on average, around 10% of body weight which, for a 12-week intervention, is fairly impressive. BMI and waist circumference went down as well, and, interestingly, much of the weight loss here was in fat mass, not fat-free mass.
Most interventions that lead to weight loss — and I’m including some of the newer drugs here — lead to both fat and muscle loss. That might not be as bad as it sounds; the truth is that muscle mass increases as fat increases because of the simple fact that if you’re carrying more weight when you walk around, your leg muscles get bigger. But to preserve muscle mass in the face of fat loss is sort of a Goldilocks finding, and, based on these results, there’s a suggestion that the high-intensity functional training helps to do just that.
The dietary intake findings were really surprising to me. Across the board, caloric intake decreased. It’s no surprise that time-restricted eating reduces calorie intake. That has been shown many times before and is probably the main reason it induces weight loss — less time to eat means you eat less.
But why would high-intensity functional training lead to lower caloric intake? Most people, myself included, get hungry after they exercise. In fact, one of the reasons it’s hard to lose weight with exercise alone is that we end up eating more calories to make up for what we lost during the exercise. This calorie reduction could be a unique effect of this type of exercise, but honestly this could also be something called the Hawthorne effect. Women in the study kept a food diary to track their intake, and the act of doing that might actually make you eat less. It makes it a little more annoying to snack a bit if you know you have to write it down. This is a situation where I would kill for a control group.
The lipid findings are also pretty striking, with around a 40% reduction in LDL across the board, and evidence of synergistic effects of combined TRE and high-intensity training on total cholesterol and triglycerides. This is like a statin level of effect — pretty impressive. Again, my heart pines for a control group, though.
Same story with glucose and insulin measures: an impressive reduction in fasting glucose and good evidence that the combination of time-restricted eating and high-intensity functional training reduces insulin levels and HOMA-IR as well.
Really the only thing that wasn’t very impressive was the change in blood pressure, with only modest decreases across the board.
Okay, so let’s take a breath after this high-intensity cerebral workout and put this all together. This was a small study, lacking a control group, but with large effect sizes in very relevant clinical areas. It confirms what we know about time-restricted eating — that it makes you eat less calories — and introduces the potential that vigorous exercise can not only magnify the benefits of time-restricted eating but maybe even mitigate some of the risks, like the risk for muscle loss. And of course, it comports with my central hypothesis, which is that the more unpleasant a lifestyle intervention is, the better it is for you. No pain, no gain, right?
Of course, I am being overly dogmatic. There are plenty of caveats. Wrestling bears is quite unpleasant and almost certainly bad for you. And there are even some pleasant things that are pretty good for you — like coffee and sex. And there are even people who find time-restricted eating and high-intensity training pleasurable. They are called masochists.
I’m joking. The truth is that Or, at least, much less painful. The trick is getting over the hump of change. If only there were a pill for that.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships. This transcript has been edited for clarity.
A version of this article appeared on Medscape.com.
Hereditary Amyloidosis: 5 Things to Know
Amyloidosis is a condition marked by the accumulation of insoluble beta-sheet fibrillar protein aggregates in tissues that can be acquired or hereditary. Hereditary amyloidogenic transthyretin (hATTR) amyloidosis is an autosomal-dominant disease caused by pathogenic variants in the TTR gene. The TTR protein is essential for transporting thyroxine and retinol-binding protein and is primarily synthesized in the liver, becoming unstable as a result of the pathogenic mutations. Inherited pathogenic variants lead to the protein’s misfolding, aggregation, and deposition as amyloid fibrils in different organs, resulting in progressive multisystem dysfunction. hATTR amyloidosis is a heterogenous disease, characterized by a wide range of clinical manifestations affecting the peripheral (both somatic and autonomic) nervous system, heart, kidneys, and central nervous system (CNS); however, the heart and peripheral nerves appear to be the main targets of the TTR-related pathologic process. Without treatment, the prognosis is poor, with an average life expectancy of 7-11 years; however, in recent years, the development of new therapeutics has brought new hope to patients.
Here are five things to know about hereditary amyloidosis.
1. Diagnosis of hereditary amyloidosis requires a high level of suspicion.
The diagnosis of hATTR amyloidosis presents a significant challenge, particularly in nonendemic regions where a lack of family history and heterogeneity of clinical presentation can delay diagnosis by 4-5 years. A timely diagnosis requires clinicians to maintain a high index of suspicion, especially when evaluating patients with neuropathic symptoms. Early diagnosis is crucial to begin patients on recently available disease-modifying therapies that can slow the disease course. Failure to recognize is the major barrier to improved patient outcomes.
Confirming the diagnosis involves detecting amyloid deposits in tissue biopsy specimens from various possible sites, including the skin, nerves, myocardium, and others. However, the diagnosis can be challenging owing to the uneven distribution of amyloid fibrils, sometimes requiring multiple biopsies or alternative diagnostic approaches, such as TTR gene sequencing, to confirm the presence of an amyloidogenic pathogenic variant. Biopsy for hATTR amyloidosis is not required if imaging of the clinical phenotype and genetic testing are consistent.
Once diagnosed, the assessment of organ involvement is essential, using nerve conduction studies, cardiac investigations (eg, echocardiography, ECG, scintigraphy), ophthalmologic assessments, and complete renal function evaluations to fully understand the extent of disease impact.
2. Hereditary amyloidosis diseases are classified into two primary categories.
Hereditary amyloidosis represents a group of diseases caused by inherited gene mutations and is classified into two main types: ATTR (transthyretin-related) and non-TTR. Most cases of hereditary amyloidosis are associated with the TTR gene. Mutations in this protein lead to different forms of ATTR amyloidosis, categorized on the basis of the specific mutation involved, such as hATTR50M (genotype Val50Met), which is the most prevalent form.
ATTR mutations result in a variety of health issues, manifesting in three primary forms:
- Neuropathic ATTR (genotype Val50Met): Early symptoms include sensorimotor polyneuropathy of the legs, carpal tunnel syndrome, autonomic dysfunction, constipation/diarrhea, and impotence; late symptoms include cardiomyopathy, vitreous opacities, glaucoma, nephropathy, and CNS symptoms.
- Cardiac ATTR (genotype Val142Ile): This type is characterized by cardiomegaly, conduction block, arrhythmia, anginal pain, congestive heart failure, and sudden death.
- Leptomeningeal ATTR (genotype Asp38Gly): This is characterized by transient focal neurologic episodes, intracerebral and/or subarachnoid hemorrhages, dementia, ataxia, and psychosis.
Non-TTR amyloidoses are rarer than are ATTR variations and involve mutations in different genes that also have significant health impacts. These include proteins such as apolipoprotein AI, fibrinogen A alpha, lysozyme, apolipoprotein AII, gelsolin, and cystatin C. Each type contributes to a range of symptoms and requires individualized management approaches.
3. Heightened disease awareness has increased the recognized prevalence of hereditary amyloidosis.
hATTR amyloidosis has historically been recognized as a rare disease, with significant clusters in Portugal, Brazil, Sweden, and Japan and alongside smaller foci in regions such as Cyprus and Majorca. This disease›s variable incidence across Europe is now perceived to be on the rise. It is attributed to heightened disease awareness among healthcare providers and the broader availability of genetic testing, extending its recognized impact to at least 29 countries globally. The genetic landscape of hATTR amyloidosis is diverse, with over 140 mutations identified in the TTR gene. Among these, the Val50Met mutation is particularly notable for its association with large patient clusters in the endemic regions.
Morbidity and mortality associated with hATTR amyloidosis are significant, with an average lifespan of 7-11 years post diagnosis; however, survival rates can vary widely depending on the specific genetic variant and organ involvement. Early diagnosis can substantially improve outcomes; yet, for many, the prognosis remains poor, especially in cases dominated by cardiomyopathy. Genetics play a central role in the disease›s transmission, with autosomal-dominant inheritance patterns and high penetrance among carriers of pathogenic mutations. Research continues to uncover the broad spectrum of genetic variations contributing to hATTR amyloidosis, with ongoing studies poised to expand our understanding of its molecular underpinnings and potential treatment options.
4. The effect on quality of life is significant both in patients living with hATTR amyloidosis and their caregivers.
hATTR amyloidosis imposes a multifaceted burden on patients and their caregivers as the disease progresses. Symptoms range from sensorimotor impairment and gastrointestinal or autonomic dysfunction to heart failure, leading to significant health-related quality-of-life deficits. The systemic nature of hATTR amyloidosis significantly affects patients› lifestyles, daily activities, and general well-being, especially because it typically manifests in adulthood — a crucial time for occupational changes. The progression of hATTR amyloidosis exacerbates the challenges in maintaining employment and managing household chores, with symptomatic patients often unable to work and experiencing difficulties with absenteeism and presenteeism when they are able to work.
hATTR amyloidosis leads to physical, mental, occupational, and social limitations for patients, and it also places a considerable strain on their families and caregivers, who report poor mental health, work impairment, and a high time commitment (mean, 45.9 h/wk) to providing care.
5. There have been significant advancements in therapeutic options for early-stage hATTR amyloidosis.
After diagnosis, prompt initiation of treatment is recommended to delay the progression of hATTR amyloidosis; a multidisciplinary approach is essential, incorporating anti-amyloid therapy to inhibit further production and/or deposition of amyloid aggregates. Treatment strategies also include addressing symptomatic therapy and managing cardiac, renal, and ocular involvement. Although many therapies have been developed, especially for the early stages of hATTR amyloidosis, therapeutic benefits for patients with advanced disease remain limited.
Recent advancements in the treatment of hATTR amyloidosis have introduced RNA-targeted therapies including patisiran, vutrisiran, and eplontersen, which have shown efficacy in reducing hepatic TTR synthesis and the aggregation of misfolded monomers into amyloid deposits. These therapies, ranging from small interfering RNA formulations to antisense oligonucleotides, offer benefits in managing both cardiomyopathy and neuropathy associated with hATTR amyloidosis , administered through various methods, including intravenous infusions and subcutaneous injections. In addition, the stabilization of TTR tetramers with the use of drugs such as tafamidis and diflunisal has effectively prevented the formation of amyloidogenic monomers. Moreover, other investigational agents, including TTR stabilizers like acoramidis and tolcapone, as well as novel compounds that inhibit amyloid formation and disrupt fibrils, are expanding the therapeutic landscape for hATTR amyloidosis , providing hope for improved management of this complex condition.
Dr. Gertz is a professor and consultant in the Department of Hematology, Mayo Clinic, Rochester, Minnesota. He has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from AstraZeneca, Ionis, and Alnylym.
A version of this article appeared on Medscape.com.
Amyloidosis is a condition marked by the accumulation of insoluble beta-sheet fibrillar protein aggregates in tissues that can be acquired or hereditary. Hereditary amyloidogenic transthyretin (hATTR) amyloidosis is an autosomal-dominant disease caused by pathogenic variants in the TTR gene. The TTR protein is essential for transporting thyroxine and retinol-binding protein and is primarily synthesized in the liver, becoming unstable as a result of the pathogenic mutations. Inherited pathogenic variants lead to the protein’s misfolding, aggregation, and deposition as amyloid fibrils in different organs, resulting in progressive multisystem dysfunction. hATTR amyloidosis is a heterogenous disease, characterized by a wide range of clinical manifestations affecting the peripheral (both somatic and autonomic) nervous system, heart, kidneys, and central nervous system (CNS); however, the heart and peripheral nerves appear to be the main targets of the TTR-related pathologic process. Without treatment, the prognosis is poor, with an average life expectancy of 7-11 years; however, in recent years, the development of new therapeutics has brought new hope to patients.
Here are five things to know about hereditary amyloidosis.
1. Diagnosis of hereditary amyloidosis requires a high level of suspicion.
The diagnosis of hATTR amyloidosis presents a significant challenge, particularly in nonendemic regions where a lack of family history and heterogeneity of clinical presentation can delay diagnosis by 4-5 years. A timely diagnosis requires clinicians to maintain a high index of suspicion, especially when evaluating patients with neuropathic symptoms. Early diagnosis is crucial to begin patients on recently available disease-modifying therapies that can slow the disease course. Failure to recognize is the major barrier to improved patient outcomes.
Confirming the diagnosis involves detecting amyloid deposits in tissue biopsy specimens from various possible sites, including the skin, nerves, myocardium, and others. However, the diagnosis can be challenging owing to the uneven distribution of amyloid fibrils, sometimes requiring multiple biopsies or alternative diagnostic approaches, such as TTR gene sequencing, to confirm the presence of an amyloidogenic pathogenic variant. Biopsy for hATTR amyloidosis is not required if imaging of the clinical phenotype and genetic testing are consistent.
Once diagnosed, the assessment of organ involvement is essential, using nerve conduction studies, cardiac investigations (eg, echocardiography, ECG, scintigraphy), ophthalmologic assessments, and complete renal function evaluations to fully understand the extent of disease impact.
2. Hereditary amyloidosis diseases are classified into two primary categories.
Hereditary amyloidosis represents a group of diseases caused by inherited gene mutations and is classified into two main types: ATTR (transthyretin-related) and non-TTR. Most cases of hereditary amyloidosis are associated with the TTR gene. Mutations in this protein lead to different forms of ATTR amyloidosis, categorized on the basis of the specific mutation involved, such as hATTR50M (genotype Val50Met), which is the most prevalent form.
ATTR mutations result in a variety of health issues, manifesting in three primary forms:
- Neuropathic ATTR (genotype Val50Met): Early symptoms include sensorimotor polyneuropathy of the legs, carpal tunnel syndrome, autonomic dysfunction, constipation/diarrhea, and impotence; late symptoms include cardiomyopathy, vitreous opacities, glaucoma, nephropathy, and CNS symptoms.
- Cardiac ATTR (genotype Val142Ile): This type is characterized by cardiomegaly, conduction block, arrhythmia, anginal pain, congestive heart failure, and sudden death.
- Leptomeningeal ATTR (genotype Asp38Gly): This is characterized by transient focal neurologic episodes, intracerebral and/or subarachnoid hemorrhages, dementia, ataxia, and psychosis.
Non-TTR amyloidoses are rarer than are ATTR variations and involve mutations in different genes that also have significant health impacts. These include proteins such as apolipoprotein AI, fibrinogen A alpha, lysozyme, apolipoprotein AII, gelsolin, and cystatin C. Each type contributes to a range of symptoms and requires individualized management approaches.
3. Heightened disease awareness has increased the recognized prevalence of hereditary amyloidosis.
hATTR amyloidosis has historically been recognized as a rare disease, with significant clusters in Portugal, Brazil, Sweden, and Japan and alongside smaller foci in regions such as Cyprus and Majorca. This disease›s variable incidence across Europe is now perceived to be on the rise. It is attributed to heightened disease awareness among healthcare providers and the broader availability of genetic testing, extending its recognized impact to at least 29 countries globally. The genetic landscape of hATTR amyloidosis is diverse, with over 140 mutations identified in the TTR gene. Among these, the Val50Met mutation is particularly notable for its association with large patient clusters in the endemic regions.
Morbidity and mortality associated with hATTR amyloidosis are significant, with an average lifespan of 7-11 years post diagnosis; however, survival rates can vary widely depending on the specific genetic variant and organ involvement. Early diagnosis can substantially improve outcomes; yet, for many, the prognosis remains poor, especially in cases dominated by cardiomyopathy. Genetics play a central role in the disease›s transmission, with autosomal-dominant inheritance patterns and high penetrance among carriers of pathogenic mutations. Research continues to uncover the broad spectrum of genetic variations contributing to hATTR amyloidosis, with ongoing studies poised to expand our understanding of its molecular underpinnings and potential treatment options.
4. The effect on quality of life is significant both in patients living with hATTR amyloidosis and their caregivers.
hATTR amyloidosis imposes a multifaceted burden on patients and their caregivers as the disease progresses. Symptoms range from sensorimotor impairment and gastrointestinal or autonomic dysfunction to heart failure, leading to significant health-related quality-of-life deficits. The systemic nature of hATTR amyloidosis significantly affects patients› lifestyles, daily activities, and general well-being, especially because it typically manifests in adulthood — a crucial time for occupational changes. The progression of hATTR amyloidosis exacerbates the challenges in maintaining employment and managing household chores, with symptomatic patients often unable to work and experiencing difficulties with absenteeism and presenteeism when they are able to work.
hATTR amyloidosis leads to physical, mental, occupational, and social limitations for patients, and it also places a considerable strain on their families and caregivers, who report poor mental health, work impairment, and a high time commitment (mean, 45.9 h/wk) to providing care.
5. There have been significant advancements in therapeutic options for early-stage hATTR amyloidosis.
After diagnosis, prompt initiation of treatment is recommended to delay the progression of hATTR amyloidosis; a multidisciplinary approach is essential, incorporating anti-amyloid therapy to inhibit further production and/or deposition of amyloid aggregates. Treatment strategies also include addressing symptomatic therapy and managing cardiac, renal, and ocular involvement. Although many therapies have been developed, especially for the early stages of hATTR amyloidosis, therapeutic benefits for patients with advanced disease remain limited.
Recent advancements in the treatment of hATTR amyloidosis have introduced RNA-targeted therapies including patisiran, vutrisiran, and eplontersen, which have shown efficacy in reducing hepatic TTR synthesis and the aggregation of misfolded monomers into amyloid deposits. These therapies, ranging from small interfering RNA formulations to antisense oligonucleotides, offer benefits in managing both cardiomyopathy and neuropathy associated with hATTR amyloidosis , administered through various methods, including intravenous infusions and subcutaneous injections. In addition, the stabilization of TTR tetramers with the use of drugs such as tafamidis and diflunisal has effectively prevented the formation of amyloidogenic monomers. Moreover, other investigational agents, including TTR stabilizers like acoramidis and tolcapone, as well as novel compounds that inhibit amyloid formation and disrupt fibrils, are expanding the therapeutic landscape for hATTR amyloidosis , providing hope for improved management of this complex condition.
Dr. Gertz is a professor and consultant in the Department of Hematology, Mayo Clinic, Rochester, Minnesota. He has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from AstraZeneca, Ionis, and Alnylym.
A version of this article appeared on Medscape.com.
Amyloidosis is a condition marked by the accumulation of insoluble beta-sheet fibrillar protein aggregates in tissues that can be acquired or hereditary. Hereditary amyloidogenic transthyretin (hATTR) amyloidosis is an autosomal-dominant disease caused by pathogenic variants in the TTR gene. The TTR protein is essential for transporting thyroxine and retinol-binding protein and is primarily synthesized in the liver, becoming unstable as a result of the pathogenic mutations. Inherited pathogenic variants lead to the protein’s misfolding, aggregation, and deposition as amyloid fibrils in different organs, resulting in progressive multisystem dysfunction. hATTR amyloidosis is a heterogenous disease, characterized by a wide range of clinical manifestations affecting the peripheral (both somatic and autonomic) nervous system, heart, kidneys, and central nervous system (CNS); however, the heart and peripheral nerves appear to be the main targets of the TTR-related pathologic process. Without treatment, the prognosis is poor, with an average life expectancy of 7-11 years; however, in recent years, the development of new therapeutics has brought new hope to patients.
Here are five things to know about hereditary amyloidosis.
1. Diagnosis of hereditary amyloidosis requires a high level of suspicion.
The diagnosis of hATTR amyloidosis presents a significant challenge, particularly in nonendemic regions where a lack of family history and heterogeneity of clinical presentation can delay diagnosis by 4-5 years. A timely diagnosis requires clinicians to maintain a high index of suspicion, especially when evaluating patients with neuropathic symptoms. Early diagnosis is crucial to begin patients on recently available disease-modifying therapies that can slow the disease course. Failure to recognize is the major barrier to improved patient outcomes.
Confirming the diagnosis involves detecting amyloid deposits in tissue biopsy specimens from various possible sites, including the skin, nerves, myocardium, and others. However, the diagnosis can be challenging owing to the uneven distribution of amyloid fibrils, sometimes requiring multiple biopsies or alternative diagnostic approaches, such as TTR gene sequencing, to confirm the presence of an amyloidogenic pathogenic variant. Biopsy for hATTR amyloidosis is not required if imaging of the clinical phenotype and genetic testing are consistent.
Once diagnosed, the assessment of organ involvement is essential, using nerve conduction studies, cardiac investigations (eg, echocardiography, ECG, scintigraphy), ophthalmologic assessments, and complete renal function evaluations to fully understand the extent of disease impact.
2. Hereditary amyloidosis diseases are classified into two primary categories.
Hereditary amyloidosis represents a group of diseases caused by inherited gene mutations and is classified into two main types: ATTR (transthyretin-related) and non-TTR. Most cases of hereditary amyloidosis are associated with the TTR gene. Mutations in this protein lead to different forms of ATTR amyloidosis, categorized on the basis of the specific mutation involved, such as hATTR50M (genotype Val50Met), which is the most prevalent form.
ATTR mutations result in a variety of health issues, manifesting in three primary forms:
- Neuropathic ATTR (genotype Val50Met): Early symptoms include sensorimotor polyneuropathy of the legs, carpal tunnel syndrome, autonomic dysfunction, constipation/diarrhea, and impotence; late symptoms include cardiomyopathy, vitreous opacities, glaucoma, nephropathy, and CNS symptoms.
- Cardiac ATTR (genotype Val142Ile): This type is characterized by cardiomegaly, conduction block, arrhythmia, anginal pain, congestive heart failure, and sudden death.
- Leptomeningeal ATTR (genotype Asp38Gly): This is characterized by transient focal neurologic episodes, intracerebral and/or subarachnoid hemorrhages, dementia, ataxia, and psychosis.
Non-TTR amyloidoses are rarer than are ATTR variations and involve mutations in different genes that also have significant health impacts. These include proteins such as apolipoprotein AI, fibrinogen A alpha, lysozyme, apolipoprotein AII, gelsolin, and cystatin C. Each type contributes to a range of symptoms and requires individualized management approaches.
3. Heightened disease awareness has increased the recognized prevalence of hereditary amyloidosis.
hATTR amyloidosis has historically been recognized as a rare disease, with significant clusters in Portugal, Brazil, Sweden, and Japan and alongside smaller foci in regions such as Cyprus and Majorca. This disease›s variable incidence across Europe is now perceived to be on the rise. It is attributed to heightened disease awareness among healthcare providers and the broader availability of genetic testing, extending its recognized impact to at least 29 countries globally. The genetic landscape of hATTR amyloidosis is diverse, with over 140 mutations identified in the TTR gene. Among these, the Val50Met mutation is particularly notable for its association with large patient clusters in the endemic regions.
Morbidity and mortality associated with hATTR amyloidosis are significant, with an average lifespan of 7-11 years post diagnosis; however, survival rates can vary widely depending on the specific genetic variant and organ involvement. Early diagnosis can substantially improve outcomes; yet, for many, the prognosis remains poor, especially in cases dominated by cardiomyopathy. Genetics play a central role in the disease›s transmission, with autosomal-dominant inheritance patterns and high penetrance among carriers of pathogenic mutations. Research continues to uncover the broad spectrum of genetic variations contributing to hATTR amyloidosis, with ongoing studies poised to expand our understanding of its molecular underpinnings and potential treatment options.
4. The effect on quality of life is significant both in patients living with hATTR amyloidosis and their caregivers.
hATTR amyloidosis imposes a multifaceted burden on patients and their caregivers as the disease progresses. Symptoms range from sensorimotor impairment and gastrointestinal or autonomic dysfunction to heart failure, leading to significant health-related quality-of-life deficits. The systemic nature of hATTR amyloidosis significantly affects patients› lifestyles, daily activities, and general well-being, especially because it typically manifests in adulthood — a crucial time for occupational changes. The progression of hATTR amyloidosis exacerbates the challenges in maintaining employment and managing household chores, with symptomatic patients often unable to work and experiencing difficulties with absenteeism and presenteeism when they are able to work.
hATTR amyloidosis leads to physical, mental, occupational, and social limitations for patients, and it also places a considerable strain on their families and caregivers, who report poor mental health, work impairment, and a high time commitment (mean, 45.9 h/wk) to providing care.
5. There have been significant advancements in therapeutic options for early-stage hATTR amyloidosis.
After diagnosis, prompt initiation of treatment is recommended to delay the progression of hATTR amyloidosis; a multidisciplinary approach is essential, incorporating anti-amyloid therapy to inhibit further production and/or deposition of amyloid aggregates. Treatment strategies also include addressing symptomatic therapy and managing cardiac, renal, and ocular involvement. Although many therapies have been developed, especially for the early stages of hATTR amyloidosis, therapeutic benefits for patients with advanced disease remain limited.
Recent advancements in the treatment of hATTR amyloidosis have introduced RNA-targeted therapies including patisiran, vutrisiran, and eplontersen, which have shown efficacy in reducing hepatic TTR synthesis and the aggregation of misfolded monomers into amyloid deposits. These therapies, ranging from small interfering RNA formulations to antisense oligonucleotides, offer benefits in managing both cardiomyopathy and neuropathy associated with hATTR amyloidosis , administered through various methods, including intravenous infusions and subcutaneous injections. In addition, the stabilization of TTR tetramers with the use of drugs such as tafamidis and diflunisal has effectively prevented the formation of amyloidogenic monomers. Moreover, other investigational agents, including TTR stabilizers like acoramidis and tolcapone, as well as novel compounds that inhibit amyloid formation and disrupt fibrils, are expanding the therapeutic landscape for hATTR amyloidosis , providing hope for improved management of this complex condition.
Dr. Gertz is a professor and consultant in the Department of Hematology, Mayo Clinic, Rochester, Minnesota. He has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from AstraZeneca, Ionis, and Alnylym.
A version of this article appeared on Medscape.com.
The AGA Future Leaders Program: A Mentee-Mentor Triad Perspective
Two of us (Parakkal Deepak and Edward L. Barnes) were part of the American Gastroenterological Association’s (AGA) Future Leaders Program (FLP) class of 2022-2023, and our mentor was Aasma Shaukat. We were invited to share our experiences as participants in the FLP and its impact in our careers.
Why Was the Future Leaders Program Conceived?
To understand this, one must first understand that the AGA, like all other GI professional organizations, relies on volunteer leaders to develop its long-term vision and execute this through strategic initiatives and programs. and understand the governance structure of the AGA to help lead it to face these challenges effectively.
The AGA FLP was thus conceived and launched in 2014-2015 by the founding chairs, Byron Cryer, MD, who is a professor of medicine and associate dean for faculty diversity at University of Texas Southwestern Medical School and Suzanne Rose, MD, MSEd, AGAF, who is a professor of medicine and senior vice dean for medical education at Perelman School of Medicine at the University of Pennsylvania. They envisioned a leadership pathway that would position early career GIs on a track to positively affect the AGA and the field of GI.
How Does One Apply for the Program?
Our FLP cohort applications were invited in October of 2021 and mentees accepted into the program in November 2021. The application process is competitive – applicants are encouraged to detail why they feel they would benefit from the FLP, what existing skillsets they have that can be further enhanced through the program, and what their long-term vision is for their growth as leaders, both within their institution and within the AGA. This is further accompanied by letters of support from their divisional chiefs and other key supervisors within the division who are intimately aware of their leadership potential and career trajectory. This process identified 18 future leaders for our class of 2022-2023.
What Is Involved?
Following acceptance into the AGA Future Leaders Program, we embarked on a series of virtual and in-person meetings with our mentorship triads (one mentor and two mentees) and other mentorship teams over the 18-month program (see Figure). These meetings covered highly focused topics ranging from the role of advocacy in leadership to negotiation and developing a business plan, with ample opportunities for individually tailored mentorship within the mentorship triads.
We also completed personality assessments that helped us understand our strengths and areas of improvement, and ways to use the information to hone our leadership styles.
A large portion of programming and the mentorship experience during the AGA Future Leaders Program is focused on a leadership project that is aimed at addressing a societal driver of interest for the AGA. Examples of these societal drivers of interest include maximizing the role of women in gastroenterology, the role of artificial intelligence in gastroenterology, burnout, and the impact of climate change on gastroenterology. Mentorship triads propose novel methods for addressing these critical issues, outlining the roles that the AGA and other stakeholders may embrace to address these anticipated growing challenges head on.
Our mentorship triad was asked to address the issue of ending disparities within gastroenterology. Given our research and clinical interest in inflammatory bowel disease (IBD), we immediately recognized an opportunity to evaluate and potentially offer solutions for the geographic disparities that exist in the field of IBD. These disparities affect access to care for patients with Crohn’s disease and ulcerative colitis, leading to delays in diagnosis and ultimately effective therapy decisions.
In addition to developing a proposal for the AGA to expand access to care to major IBD centers in rural areas where these disparities exist, we also initiated an examination of geographic disparities in our own multidisciplinary IBD centers (abstract accepted for presentation at Digestive Diseases Week 2024). This allowed us to expand our respective research footprints at our institutions, utilizing new methods of geocoding to directly measure factors affecting clinical outcomes in IBD. Given our in-depth evaluation of this topic as part of our Future Leaders Program training, at the suggestion of our mentor, our mentorship triad also published a commentary on geographic disparities in the Diversity, Equity, and Inclusion sections of Gastroenterology and Clinical Gastroenterology and Hepatology.1, 2
Impact on the Field and Our Careers
Our mentorship triad had the unique experience of having a mentor who had previously participated in the Future Leaders Program as a mentee. As the Future Leaders Program has now enrolled 72 participants, these occasions will likely become more frequent, given the opportunities for career development and growth within the AGA (and our field) that are available after participating in the Future Leaders Program.
To have a mentor with this insight of having been a mentee in the program was invaluable, given her direct experience and understanding of the growth opportunities available, and opportunities to maximize participation in the Future Leaders Program. Additionally, as evidenced by Dr. Shaukat’s recommendations to grow our initial assignment into published commentaries, need statements for our field, and ultimately growing research projects, her keen insights as a mentor were a critical component of our individual growth in the program and the success of our mentorship triad. We benefited from networking with peers and learning about their work, which can lead to future collaborations. We had access to the highly accomplished mentors from diverse settings and learned models of leadership, while developing skills to foster our own leadership style.
In terms of programmatic impact, more than 90% of FLP alumni are serving in AGA leadership on committees, task forces, editorial boards, and councils. What is also important is the impact of content developed by mentee-mentor triads during the FLP cohorts over time. More than 700 GIs have benefited from online leadership development content created by the FLP. Based on our experience, we highly recommend all early career GI physicians to apply!
Dr. Parakkal (@P_DeepakIBDMD) is based in the division of gastroenterology, Washington University in St. Louis (Mo.) School of Medicine. He is supported by a Junior Faculty Development Award from the American College of Gastroenterology and IBD Plexus of the Crohn’s & Colitis Foundation. He has received research support under a sponsored research agreement unrelated to the data in the paper from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Prometheus Biosciences, Takeda Pharmaceuticals, Roche-Genentech, and CorEvitas LLC. He has served as a consultant for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Scipher Medicine, Fresenius Kabi, Roche-Genentech, and CorEvitas LLC. Dr. Barnes (@EdBarnesMD) is based in the division of gastroenterology and hepatology, University of North Carolina at Chapel Hill. He is supported by National Institutes of Health K23DK127157-01, and has served as a consultant for Eli Lilly, Bristol-Meyers Squibb, and Target RWE. Dr. Shaukat (@AasmaShaukatMD) is based in the division of gastroenterology, New York University, New York. She has served as a consultant for Iterative health, Motus, Freenome, and Geneoscopy. Research support by the Steve and Alex Cohen Foundation.
References
1. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Gastroenterology. 2023 July. doi: 10.1053/j.gastro.2023.05.017.
2. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Clin Gastroenterol Hepatol. 2023 July. doi: 10.1016/j.cgh.2023.04.006.
Two of us (Parakkal Deepak and Edward L. Barnes) were part of the American Gastroenterological Association’s (AGA) Future Leaders Program (FLP) class of 2022-2023, and our mentor was Aasma Shaukat. We were invited to share our experiences as participants in the FLP and its impact in our careers.
Why Was the Future Leaders Program Conceived?
To understand this, one must first understand that the AGA, like all other GI professional organizations, relies on volunteer leaders to develop its long-term vision and execute this through strategic initiatives and programs. and understand the governance structure of the AGA to help lead it to face these challenges effectively.
The AGA FLP was thus conceived and launched in 2014-2015 by the founding chairs, Byron Cryer, MD, who is a professor of medicine and associate dean for faculty diversity at University of Texas Southwestern Medical School and Suzanne Rose, MD, MSEd, AGAF, who is a professor of medicine and senior vice dean for medical education at Perelman School of Medicine at the University of Pennsylvania. They envisioned a leadership pathway that would position early career GIs on a track to positively affect the AGA and the field of GI.
How Does One Apply for the Program?
Our FLP cohort applications were invited in October of 2021 and mentees accepted into the program in November 2021. The application process is competitive – applicants are encouraged to detail why they feel they would benefit from the FLP, what existing skillsets they have that can be further enhanced through the program, and what their long-term vision is for their growth as leaders, both within their institution and within the AGA. This is further accompanied by letters of support from their divisional chiefs and other key supervisors within the division who are intimately aware of their leadership potential and career trajectory. This process identified 18 future leaders for our class of 2022-2023.
What Is Involved?
Following acceptance into the AGA Future Leaders Program, we embarked on a series of virtual and in-person meetings with our mentorship triads (one mentor and two mentees) and other mentorship teams over the 18-month program (see Figure). These meetings covered highly focused topics ranging from the role of advocacy in leadership to negotiation and developing a business plan, with ample opportunities for individually tailored mentorship within the mentorship triads.
We also completed personality assessments that helped us understand our strengths and areas of improvement, and ways to use the information to hone our leadership styles.
A large portion of programming and the mentorship experience during the AGA Future Leaders Program is focused on a leadership project that is aimed at addressing a societal driver of interest for the AGA. Examples of these societal drivers of interest include maximizing the role of women in gastroenterology, the role of artificial intelligence in gastroenterology, burnout, and the impact of climate change on gastroenterology. Mentorship triads propose novel methods for addressing these critical issues, outlining the roles that the AGA and other stakeholders may embrace to address these anticipated growing challenges head on.
Our mentorship triad was asked to address the issue of ending disparities within gastroenterology. Given our research and clinical interest in inflammatory bowel disease (IBD), we immediately recognized an opportunity to evaluate and potentially offer solutions for the geographic disparities that exist in the field of IBD. These disparities affect access to care for patients with Crohn’s disease and ulcerative colitis, leading to delays in diagnosis and ultimately effective therapy decisions.
In addition to developing a proposal for the AGA to expand access to care to major IBD centers in rural areas where these disparities exist, we also initiated an examination of geographic disparities in our own multidisciplinary IBD centers (abstract accepted for presentation at Digestive Diseases Week 2024). This allowed us to expand our respective research footprints at our institutions, utilizing new methods of geocoding to directly measure factors affecting clinical outcomes in IBD. Given our in-depth evaluation of this topic as part of our Future Leaders Program training, at the suggestion of our mentor, our mentorship triad also published a commentary on geographic disparities in the Diversity, Equity, and Inclusion sections of Gastroenterology and Clinical Gastroenterology and Hepatology.1, 2
Impact on the Field and Our Careers
Our mentorship triad had the unique experience of having a mentor who had previously participated in the Future Leaders Program as a mentee. As the Future Leaders Program has now enrolled 72 participants, these occasions will likely become more frequent, given the opportunities for career development and growth within the AGA (and our field) that are available after participating in the Future Leaders Program.
To have a mentor with this insight of having been a mentee in the program was invaluable, given her direct experience and understanding of the growth opportunities available, and opportunities to maximize participation in the Future Leaders Program. Additionally, as evidenced by Dr. Shaukat’s recommendations to grow our initial assignment into published commentaries, need statements for our field, and ultimately growing research projects, her keen insights as a mentor were a critical component of our individual growth in the program and the success of our mentorship triad. We benefited from networking with peers and learning about their work, which can lead to future collaborations. We had access to the highly accomplished mentors from diverse settings and learned models of leadership, while developing skills to foster our own leadership style.
In terms of programmatic impact, more than 90% of FLP alumni are serving in AGA leadership on committees, task forces, editorial boards, and councils. What is also important is the impact of content developed by mentee-mentor triads during the FLP cohorts over time. More than 700 GIs have benefited from online leadership development content created by the FLP. Based on our experience, we highly recommend all early career GI physicians to apply!
Dr. Parakkal (@P_DeepakIBDMD) is based in the division of gastroenterology, Washington University in St. Louis (Mo.) School of Medicine. He is supported by a Junior Faculty Development Award from the American College of Gastroenterology and IBD Plexus of the Crohn’s & Colitis Foundation. He has received research support under a sponsored research agreement unrelated to the data in the paper from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Prometheus Biosciences, Takeda Pharmaceuticals, Roche-Genentech, and CorEvitas LLC. He has served as a consultant for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Scipher Medicine, Fresenius Kabi, Roche-Genentech, and CorEvitas LLC. Dr. Barnes (@EdBarnesMD) is based in the division of gastroenterology and hepatology, University of North Carolina at Chapel Hill. He is supported by National Institutes of Health K23DK127157-01, and has served as a consultant for Eli Lilly, Bristol-Meyers Squibb, and Target RWE. Dr. Shaukat (@AasmaShaukatMD) is based in the division of gastroenterology, New York University, New York. She has served as a consultant for Iterative health, Motus, Freenome, and Geneoscopy. Research support by the Steve and Alex Cohen Foundation.
References
1. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Gastroenterology. 2023 July. doi: 10.1053/j.gastro.2023.05.017.
2. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Clin Gastroenterol Hepatol. 2023 July. doi: 10.1016/j.cgh.2023.04.006.
Two of us (Parakkal Deepak and Edward L. Barnes) were part of the American Gastroenterological Association’s (AGA) Future Leaders Program (FLP) class of 2022-2023, and our mentor was Aasma Shaukat. We were invited to share our experiences as participants in the FLP and its impact in our careers.
Why Was the Future Leaders Program Conceived?
To understand this, one must first understand that the AGA, like all other GI professional organizations, relies on volunteer leaders to develop its long-term vision and execute this through strategic initiatives and programs. and understand the governance structure of the AGA to help lead it to face these challenges effectively.
The AGA FLP was thus conceived and launched in 2014-2015 by the founding chairs, Byron Cryer, MD, who is a professor of medicine and associate dean for faculty diversity at University of Texas Southwestern Medical School and Suzanne Rose, MD, MSEd, AGAF, who is a professor of medicine and senior vice dean for medical education at Perelman School of Medicine at the University of Pennsylvania. They envisioned a leadership pathway that would position early career GIs on a track to positively affect the AGA and the field of GI.
How Does One Apply for the Program?
Our FLP cohort applications were invited in October of 2021 and mentees accepted into the program in November 2021. The application process is competitive – applicants are encouraged to detail why they feel they would benefit from the FLP, what existing skillsets they have that can be further enhanced through the program, and what their long-term vision is for their growth as leaders, both within their institution and within the AGA. This is further accompanied by letters of support from their divisional chiefs and other key supervisors within the division who are intimately aware of their leadership potential and career trajectory. This process identified 18 future leaders for our class of 2022-2023.
What Is Involved?
Following acceptance into the AGA Future Leaders Program, we embarked on a series of virtual and in-person meetings with our mentorship triads (one mentor and two mentees) and other mentorship teams over the 18-month program (see Figure). These meetings covered highly focused topics ranging from the role of advocacy in leadership to negotiation and developing a business plan, with ample opportunities for individually tailored mentorship within the mentorship triads.
We also completed personality assessments that helped us understand our strengths and areas of improvement, and ways to use the information to hone our leadership styles.
A large portion of programming and the mentorship experience during the AGA Future Leaders Program is focused on a leadership project that is aimed at addressing a societal driver of interest for the AGA. Examples of these societal drivers of interest include maximizing the role of women in gastroenterology, the role of artificial intelligence in gastroenterology, burnout, and the impact of climate change on gastroenterology. Mentorship triads propose novel methods for addressing these critical issues, outlining the roles that the AGA and other stakeholders may embrace to address these anticipated growing challenges head on.
Our mentorship triad was asked to address the issue of ending disparities within gastroenterology. Given our research and clinical interest in inflammatory bowel disease (IBD), we immediately recognized an opportunity to evaluate and potentially offer solutions for the geographic disparities that exist in the field of IBD. These disparities affect access to care for patients with Crohn’s disease and ulcerative colitis, leading to delays in diagnosis and ultimately effective therapy decisions.
In addition to developing a proposal for the AGA to expand access to care to major IBD centers in rural areas where these disparities exist, we also initiated an examination of geographic disparities in our own multidisciplinary IBD centers (abstract accepted for presentation at Digestive Diseases Week 2024). This allowed us to expand our respective research footprints at our institutions, utilizing new methods of geocoding to directly measure factors affecting clinical outcomes in IBD. Given our in-depth evaluation of this topic as part of our Future Leaders Program training, at the suggestion of our mentor, our mentorship triad also published a commentary on geographic disparities in the Diversity, Equity, and Inclusion sections of Gastroenterology and Clinical Gastroenterology and Hepatology.1, 2
Impact on the Field and Our Careers
Our mentorship triad had the unique experience of having a mentor who had previously participated in the Future Leaders Program as a mentee. As the Future Leaders Program has now enrolled 72 participants, these occasions will likely become more frequent, given the opportunities for career development and growth within the AGA (and our field) that are available after participating in the Future Leaders Program.
To have a mentor with this insight of having been a mentee in the program was invaluable, given her direct experience and understanding of the growth opportunities available, and opportunities to maximize participation in the Future Leaders Program. Additionally, as evidenced by Dr. Shaukat’s recommendations to grow our initial assignment into published commentaries, need statements for our field, and ultimately growing research projects, her keen insights as a mentor were a critical component of our individual growth in the program and the success of our mentorship triad. We benefited from networking with peers and learning about their work, which can lead to future collaborations. We had access to the highly accomplished mentors from diverse settings and learned models of leadership, while developing skills to foster our own leadership style.
In terms of programmatic impact, more than 90% of FLP alumni are serving in AGA leadership on committees, task forces, editorial boards, and councils. What is also important is the impact of content developed by mentee-mentor triads during the FLP cohorts over time. More than 700 GIs have benefited from online leadership development content created by the FLP. Based on our experience, we highly recommend all early career GI physicians to apply!
Dr. Parakkal (@P_DeepakIBDMD) is based in the division of gastroenterology, Washington University in St. Louis (Mo.) School of Medicine. He is supported by a Junior Faculty Development Award from the American College of Gastroenterology and IBD Plexus of the Crohn’s & Colitis Foundation. He has received research support under a sponsored research agreement unrelated to the data in the paper from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Prometheus Biosciences, Takeda Pharmaceuticals, Roche-Genentech, and CorEvitas LLC. He has served as a consultant for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Scipher Medicine, Fresenius Kabi, Roche-Genentech, and CorEvitas LLC. Dr. Barnes (@EdBarnesMD) is based in the division of gastroenterology and hepatology, University of North Carolina at Chapel Hill. He is supported by National Institutes of Health K23DK127157-01, and has served as a consultant for Eli Lilly, Bristol-Meyers Squibb, and Target RWE. Dr. Shaukat (@AasmaShaukatMD) is based in the division of gastroenterology, New York University, New York. She has served as a consultant for Iterative health, Motus, Freenome, and Geneoscopy. Research support by the Steve and Alex Cohen Foundation.
References
1. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Gastroenterology. 2023 July. doi: 10.1053/j.gastro.2023.05.017.
2. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Clin Gastroenterol Hepatol. 2023 July. doi: 10.1016/j.cgh.2023.04.006.
Artificial Intelligence in GI and Hepatology
Dear colleagues,
Since our prior Perspectives piece on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. Expectations are high that AI will revolutionize our field and significantly improve patient care. But as the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.
In this issue, Dr. Nabil M. Mansour and Dr. Thomas R. McCarty explore the current and future impact of AI on gastroenterology, while Dr. Basile Njei and Yazan A. Al Ajlouni assess its role in hepatology. We hope these pieces will help your discussions in incorporating or researching AI for use in your own practices. We welcome your thoughts on this issue on X @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.
Artificial Intelligence in Gastrointestinal Endoscopy
BY THOMAS R. MCCARTY, MD, MPH; NABIL M. MANSOUR, MD
The last few decades have seen an exponential increase and interest in the role of artificial intelligence (AI) and adoption of deep learning algorithms within healthcare and patient care services. The field of gastroenterology and endoscopy has similarly seen a tremendous uptake in acceptance and implementation of AI for a variety of gastrointestinal conditions. The spectrum of AI-based applications includes detection or diagnostic-based as well as therapeutic assistance tools. From the first US Food and Drug Administration (FDA)-approved device that uses machine learning to assist clinicians in detecting lesions during colonoscopy, to other more innovative machine learning techniques for small bowel, esophageal, and hepatobiliary conditions, AI has dramatically changed the landscape of gastrointestinal endoscopy.
Approved applications for colorectal cancer
In an attempt to improve colorectal cancer screening and outcomes related to screening and surveillance, efforts have been focused on procedural performance metrics, quality indicators, and tools to aid in lesion detection and improve quality of care. One such tool has been computer-aided detection (CADe), with early randomized controlled trial (RCT) data showing significantly increased adenoma detection rate (ADR) and adenomas per colonoscopy (APC).1-3
Ultimately, this data led to FDA approval of the CADe system GI Genius (Medtronic, Dublin, Ireland) in 2021.4 Additional systems have since been FDA approved or 510(k) cleared including Endoscreener (Wision AI, Shanghai, China), SKOUT (Iterative Health, Cambridge, Massachusetts), MAGENTIQ-COLO (MAGENTIQ-EYE LTD, Haifa, Israel), and CAD EYE (Fujifilm, Tokyo), all of which have shown increased ADR and/or increased APC and/or reduced adenoma miss rates in randomized trials.5
Yet despite the promise of improved quality and subsequent translation to better patient outcomes, there has been a noticeable disconnect between RCT data and more real-world literature.6 In a recent study, no improvement was seen in ADR after implementation of a CADe system for colorectal cancer screening — including both higher and lower-ADR performers. Looking at change over time after implementation, CADe had no positive effect in any group over time, divergent from early RCT data. In a more recent multicenter, community-based RCT study, again CADe did not result in a statistically significant difference in the number of adenomas detected.7 The differences between some of these more recent “real-world” studies vs the majority of data from RCTs raise important questions regarding the potential of bias (due to unblinding) in prospective trials, as well as the role of the human-AI interaction.
Importantly for RCT data, both cohorts in these studies met adequate ADR benchmarks, though it remains unclear whether a truly increased ADR necessitates better patient outcomes — is higher always better? In addition, an important consideration with evaluating any AI/CADe system is that they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using an outdated version of a CADe system.
Additional unanswered questions regarding an ideal ADR for implementation, preferred patient populations for screening (especially for younger individuals), and the role and adoption of computer-aided polyp diagnosis/characterization (CADx) within the United States remain. Furthermore, questions regarding procedural withdrawal time, impact on sessile serrated lesion detection, cost-effectiveness, and preferred adoption strategies have begun to be explored, though require more data to better define a best practice approach. Ultimately, answers to some of these unknowns may explain the discordant results and help guide future implementation measures.
Innovative applications for alternative gastrointestinal conditions
Given the fervor and excitement, as well as the outcomes associated with AI-based colorectal screening, it is not surprising these techniques have been expanded to other gastrointestinal conditions. At this time, all of these are fledgling, mostly single-center tools, not yet ready for widespread adoption. Nonetheless, these represent a potentially important step forward for difficult-to-manage gastrointestinal diseases.
Machine learning CADe systems have been developed to help identify early Barrett’s neoplasia, depth and invasion of gastric cancer, as well as lesion detection in small bowel video capsule endoscopy.8-10 Endoscopic retrograde cholangiopancreatography (ERCP)-based applications for cholangiocarcinoma and indeterminate stricture diagnosis have also been studied.11 Additional AI-based algorithms have been employed for complex procedures such as endoscopic submucosal dissection (ESD) or peroral endoscopic myotomy (POEM) to delineate vessels, better define tissue planes for dissection, and visualize landmark structures.12,13 Furthermore, AI-based scope guidance/manipulation, bleeding detection, landmark identification, and lesion detection have the potential to revolutionize endoscopic training and education. The impact that generative AI can potentially have on clinical practice is also an exciting prospect that warrants further investigation.
Artificial intelligence adoption in clinical practice
Clinical practice with regard to AI and colorectal cancer screening largely mirrors the disconnect in the current literature, with “believers” and “non-believers” as well as innovators and early adopters alongside laggards. In our own academic practices, we continue to struggle with the adoption and standardized implementation of AI-based colorectal cancer CADe systems, despite the RCT data showing positive results. It is likely that AI uptake will follow the technology predictions of Amara’s Law — i.e., individuals tend to overestimate the short-term impact of new technologies while underestimating long-term effects. In the end, more widespread adoption in community practice and larger scale real-world clinical outcomes studies are likely to determine the true impact of these exciting technologies. For other, less established AI-based tools, more data are currently required.
Conclusions
Ultimately, AI-based algorithms are likely here to stay, with continued improvement and evolution to occur based on provider feedback and patient care needs. Current tools, while not all-encompassing, have the potential to dramatically change the landscape of endoscopic training, diagnostic evaluation, and therapeutic care. It is critically important that relevant stakeholders, both endoscopists and patients, be involved in future applications and design to improve efficiency and quality outcomes overall.
Dr. McCarty is based in the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital. Dr. Mansour is based in the section of gastroenterology, Baylor College of Medicine, Houston. Dr. McCarty reports no conflicts of interest. Dr. Mansour reports having been a consultant for Iterative Health.
References
1. Repici A, et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology. 2020 Aug. doi: 10.1053/j.gastro.2020.04.062.
2. Repici A, et al. Artificial intelligence and colonoscopy experience: Lessons from two randomised trials. Gut. Apr 2022. doi: 10.1136/gutjnl-2021-324471.
3. Wallace MB, et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology 2022 Jul. doi: 10.1053/j.gastro.2022.03.007.
4. United States Food and Drug Administration (FDA). GI Genius FDA Approval [April 9, 2021]. Accessed January 5, 2022. Available at: www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf.
5. Maas MHJ, et al. A computer-aided polyp detection system in screening and surveillance colonoscopy: An international, multicentre, randomised, tandem trial. Lancet Digit Health. 2024 Mar. doi: 10.1016/S2589-7500(23)00242-X.
6. Ladabaum U, et al. Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology. 2023 Mar. doi: 10.1053/j.gastro.2022.12.004.
7. Wei MT, et al. Evaluation of computer-aided detection during colonoscopy in the community (AI-SEE): A multicenter randomized clinical trial. Am J Gastroenterol. 2023 Oct. doi: 10.14309/ajg.0000000000002239.
8. de Groof J, et al. The Argos project: The development of a computer-aided detection system to improve detection of Barrett’s neoplasia on white light endoscopy. United European Gastroenterol J. 2019 May. doi: 10.1177/2050640619837443.
9. Kanesaka T, et al. Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging. Gastrointest Endosc. 2018 May. doi: 10.1016/j.gie.2017.11.029.
10. Sahafi A, et al. Edge artificial intelligence wireless video capsule endoscopy. Sci Rep. 2022 Aug. doi: 10.1038/s41598-022-17502-7.
11. Njei B, et al. Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: A systematic review. Ann Gastroenterol. 2023 Mar-Apr. doi: 10.20524/aog.2023.0779.
12. Ebigbo A, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut. 2022 Dec. doi: 10.1136/gutjnl-2021-326470.
13. Cao J, et al. Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study. Nat Commun. 2023 Oct. doi: 10.1038/s41467-023-42451-8.
The Promise and Challenges of AI in Hepatology
BY BASILE NJEI, MD, MPH, PHD; YAZAN A. AL-AJLOUNI, MPHIL
In the dynamic realm of medicine, artificial intelligence (AI) emerges as a transformative force, notably within hepatology. The discipline of hepatology, dedicated to liver and related organ diseases, is ripe for AI’s promise to revolutionize diagnostics and treatment, pushing toward a future of precision medicine. Yet, the path to fully realizing AI’s potential in hepatology is laced with data, ethical, and integration challenges.
The application of AI, particularly in histopathology, significantly enhances disease diagnosis and staging in hepatology. AI-driven approaches remedy traditional histopathological challenges, such as interpretative variability, providing more consistent and accurate disease analyses. This is especially evident in conditions like metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), where AI aids in identifying critical gene signatures, thereby refining therapy selection.
Similarly, deep learning (DL), a branch of AI, has attracted significant interest globally, particularly in image recognition. AI’s incorporation into medical imaging marks a significant advancement, enabling early detection of malignancies like HCC and improving diagnostics in steatotic liver disease through enhanced imaging analyses using convolutional neural networks (CNN). The abundance of imaging data alongside clinical outcomes has catalyzed AI’s integration into radiology, leading to the swift growth of radiomics as a novel domain in medical research.
AI has also been shown to identify nuanced alterations in electrocardiograms (EKGs) associated with liver conditions, potentially detecting the progression of liver diseases at an earlier stage than currently possible. By leveraging complex algorithms and machine learning, AI can analyze EKG patterns with a precision and depth unattainable through traditional manual interpretation. Given that liver diseases, such as cirrhosis or hepatitis, can induce subtle cardiac changes long before other clinical symptoms manifest, early detection through AI-enhanced EKG analysis could lead to timely interventions, potentially halting or reversing disease progression. This approach further enriches our understanding of the intricate interplay between liver function and cardiac health, highlighting the potential for AI to transform not just liver disease diagnostics but also to foster a more integrated approach to patient care.
Beyond diagnostics, the burgeoning field of generative AI introduces groundbreaking possibilities in treatment planning and patient education, particularly for chronic conditions like cirrhosis. Generative AI produces original content, including text, visuals, and music, by identifying and learning patterns from its training data. When it leverages large language models (LLMs), it entails training on vast collections of textual data and using AI models characterized by many parameters. A notable instance of generative AI employing LLMs is ChatGPT (General Pretrained Transformers). By simulating disease progression and treatment outcomes, generative AI can foster personalized treatment strategies and empower patients with knowledge about their health trajectories. Yet, realizing these potential demands requires overcoming data quality and interpretability challenges, and ensuring AI outputs are accessible and actionable for clinicians and patients.
Despite these advancements, leveraging AI in hepatology is not devoid of hurdles. The development and training of AI models require extensive and diverse datasets, raising concerns about data privacy and ethical use. Addressing these concerns is paramount for successfully integrating AI into clinical hepatology practice, necessitating transparent algorithmic processes and stringent ethical standards. Ethical considerations are central to AI’s integration into hepatology. Algorithmic biases, patient privacy, and the impact of AI-driven decisions underscore the need for cautious AI deployment. Developing transparent, understandable algorithms and establishing ethical guidelines for AI use are critical steps towards ethically leveraging AI in patient care.
In conclusion, AI’s integration into hepatology holds tremendous promise for advancing patient care through enhanced diagnostics, treatment planning, and patient education. Overcoming the associated challenges, including ethical concerns, data diversity, and algorithm interpretability, is crucial. As the hepatology community navigates this technological evolution, a balanced approach that marries technological advancements with ethical stewardship will be key to harnessing AI’s full potential, ensuring it serves the best interests of patients and propels the field of hepatology into the future.
We predict a trajectory of increased use and adoption of AI in hepatology. AI in hepatology is likely to meet the test of pervasiveness, improvement, and innovation. The adoption of AI in routine hepatology diagnosis and management will likely follow Amara’s law and the five stages of the hype cycle. We believe that we are still in the infant stages of adopting AI technology in hepatology, and this phase may last 5 years before there is a peak of inflated expectations. The trough of disillusionment and slopes of enlightenment may only be observed in the next decades.
Dr. Njei is based in the Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn. Mr. Al-Ajlouni is a senior medical student at New York Medical College School of Medicine, Valhalla, N.Y. They have no conflicts of interest to declare.
Sources
Taylor-Weiner A, et al. A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH. Hepatology. 2021 Jul. doi: 10.1002/hep.31750.
Zeng Q, et al. Artificial intelligence predicts immune and inflammatory gene signatures directly from hepatocellular carcinoma histology. J Hepatol. 2022 Jul. doi: 10.1016/j.jhep.2022.01.018.
Ahn JC, et al. Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis. Am J Gastroenterol. 2022 Mar. doi: 10.14309/ajg.0000000000001617.
Nduma BN, et al. The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review. Cureus. 2023 Dec 15. doi: 10.7759/cureus.50601.
Dear colleagues,
Since our prior Perspectives piece on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. Expectations are high that AI will revolutionize our field and significantly improve patient care. But as the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.
In this issue, Dr. Nabil M. Mansour and Dr. Thomas R. McCarty explore the current and future impact of AI on gastroenterology, while Dr. Basile Njei and Yazan A. Al Ajlouni assess its role in hepatology. We hope these pieces will help your discussions in incorporating or researching AI for use in your own practices. We welcome your thoughts on this issue on X @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.
Artificial Intelligence in Gastrointestinal Endoscopy
BY THOMAS R. MCCARTY, MD, MPH; NABIL M. MANSOUR, MD
The last few decades have seen an exponential increase and interest in the role of artificial intelligence (AI) and adoption of deep learning algorithms within healthcare and patient care services. The field of gastroenterology and endoscopy has similarly seen a tremendous uptake in acceptance and implementation of AI for a variety of gastrointestinal conditions. The spectrum of AI-based applications includes detection or diagnostic-based as well as therapeutic assistance tools. From the first US Food and Drug Administration (FDA)-approved device that uses machine learning to assist clinicians in detecting lesions during colonoscopy, to other more innovative machine learning techniques for small bowel, esophageal, and hepatobiliary conditions, AI has dramatically changed the landscape of gastrointestinal endoscopy.
Approved applications for colorectal cancer
In an attempt to improve colorectal cancer screening and outcomes related to screening and surveillance, efforts have been focused on procedural performance metrics, quality indicators, and tools to aid in lesion detection and improve quality of care. One such tool has been computer-aided detection (CADe), with early randomized controlled trial (RCT) data showing significantly increased adenoma detection rate (ADR) and adenomas per colonoscopy (APC).1-3
Ultimately, this data led to FDA approval of the CADe system GI Genius (Medtronic, Dublin, Ireland) in 2021.4 Additional systems have since been FDA approved or 510(k) cleared including Endoscreener (Wision AI, Shanghai, China), SKOUT (Iterative Health, Cambridge, Massachusetts), MAGENTIQ-COLO (MAGENTIQ-EYE LTD, Haifa, Israel), and CAD EYE (Fujifilm, Tokyo), all of which have shown increased ADR and/or increased APC and/or reduced adenoma miss rates in randomized trials.5
Yet despite the promise of improved quality and subsequent translation to better patient outcomes, there has been a noticeable disconnect between RCT data and more real-world literature.6 In a recent study, no improvement was seen in ADR after implementation of a CADe system for colorectal cancer screening — including both higher and lower-ADR performers. Looking at change over time after implementation, CADe had no positive effect in any group over time, divergent from early RCT data. In a more recent multicenter, community-based RCT study, again CADe did not result in a statistically significant difference in the number of adenomas detected.7 The differences between some of these more recent “real-world” studies vs the majority of data from RCTs raise important questions regarding the potential of bias (due to unblinding) in prospective trials, as well as the role of the human-AI interaction.
Importantly for RCT data, both cohorts in these studies met adequate ADR benchmarks, though it remains unclear whether a truly increased ADR necessitates better patient outcomes — is higher always better? In addition, an important consideration with evaluating any AI/CADe system is that they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using an outdated version of a CADe system.
Additional unanswered questions regarding an ideal ADR for implementation, preferred patient populations for screening (especially for younger individuals), and the role and adoption of computer-aided polyp diagnosis/characterization (CADx) within the United States remain. Furthermore, questions regarding procedural withdrawal time, impact on sessile serrated lesion detection, cost-effectiveness, and preferred adoption strategies have begun to be explored, though require more data to better define a best practice approach. Ultimately, answers to some of these unknowns may explain the discordant results and help guide future implementation measures.
Innovative applications for alternative gastrointestinal conditions
Given the fervor and excitement, as well as the outcomes associated with AI-based colorectal screening, it is not surprising these techniques have been expanded to other gastrointestinal conditions. At this time, all of these are fledgling, mostly single-center tools, not yet ready for widespread adoption. Nonetheless, these represent a potentially important step forward for difficult-to-manage gastrointestinal diseases.
Machine learning CADe systems have been developed to help identify early Barrett’s neoplasia, depth and invasion of gastric cancer, as well as lesion detection in small bowel video capsule endoscopy.8-10 Endoscopic retrograde cholangiopancreatography (ERCP)-based applications for cholangiocarcinoma and indeterminate stricture diagnosis have also been studied.11 Additional AI-based algorithms have been employed for complex procedures such as endoscopic submucosal dissection (ESD) or peroral endoscopic myotomy (POEM) to delineate vessels, better define tissue planes for dissection, and visualize landmark structures.12,13 Furthermore, AI-based scope guidance/manipulation, bleeding detection, landmark identification, and lesion detection have the potential to revolutionize endoscopic training and education. The impact that generative AI can potentially have on clinical practice is also an exciting prospect that warrants further investigation.
Artificial intelligence adoption in clinical practice
Clinical practice with regard to AI and colorectal cancer screening largely mirrors the disconnect in the current literature, with “believers” and “non-believers” as well as innovators and early adopters alongside laggards. In our own academic practices, we continue to struggle with the adoption and standardized implementation of AI-based colorectal cancer CADe systems, despite the RCT data showing positive results. It is likely that AI uptake will follow the technology predictions of Amara’s Law — i.e., individuals tend to overestimate the short-term impact of new technologies while underestimating long-term effects. In the end, more widespread adoption in community practice and larger scale real-world clinical outcomes studies are likely to determine the true impact of these exciting technologies. For other, less established AI-based tools, more data are currently required.
Conclusions
Ultimately, AI-based algorithms are likely here to stay, with continued improvement and evolution to occur based on provider feedback and patient care needs. Current tools, while not all-encompassing, have the potential to dramatically change the landscape of endoscopic training, diagnostic evaluation, and therapeutic care. It is critically important that relevant stakeholders, both endoscopists and patients, be involved in future applications and design to improve efficiency and quality outcomes overall.
Dr. McCarty is based in the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital. Dr. Mansour is based in the section of gastroenterology, Baylor College of Medicine, Houston. Dr. McCarty reports no conflicts of interest. Dr. Mansour reports having been a consultant for Iterative Health.
References
1. Repici A, et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology. 2020 Aug. doi: 10.1053/j.gastro.2020.04.062.
2. Repici A, et al. Artificial intelligence and colonoscopy experience: Lessons from two randomised trials. Gut. Apr 2022. doi: 10.1136/gutjnl-2021-324471.
3. Wallace MB, et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology 2022 Jul. doi: 10.1053/j.gastro.2022.03.007.
4. United States Food and Drug Administration (FDA). GI Genius FDA Approval [April 9, 2021]. Accessed January 5, 2022. Available at: www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf.
5. Maas MHJ, et al. A computer-aided polyp detection system in screening and surveillance colonoscopy: An international, multicentre, randomised, tandem trial. Lancet Digit Health. 2024 Mar. doi: 10.1016/S2589-7500(23)00242-X.
6. Ladabaum U, et al. Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology. 2023 Mar. doi: 10.1053/j.gastro.2022.12.004.
7. Wei MT, et al. Evaluation of computer-aided detection during colonoscopy in the community (AI-SEE): A multicenter randomized clinical trial. Am J Gastroenterol. 2023 Oct. doi: 10.14309/ajg.0000000000002239.
8. de Groof J, et al. The Argos project: The development of a computer-aided detection system to improve detection of Barrett’s neoplasia on white light endoscopy. United European Gastroenterol J. 2019 May. doi: 10.1177/2050640619837443.
9. Kanesaka T, et al. Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging. Gastrointest Endosc. 2018 May. doi: 10.1016/j.gie.2017.11.029.
10. Sahafi A, et al. Edge artificial intelligence wireless video capsule endoscopy. Sci Rep. 2022 Aug. doi: 10.1038/s41598-022-17502-7.
11. Njei B, et al. Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: A systematic review. Ann Gastroenterol. 2023 Mar-Apr. doi: 10.20524/aog.2023.0779.
12. Ebigbo A, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut. 2022 Dec. doi: 10.1136/gutjnl-2021-326470.
13. Cao J, et al. Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study. Nat Commun. 2023 Oct. doi: 10.1038/s41467-023-42451-8.
The Promise and Challenges of AI in Hepatology
BY BASILE NJEI, MD, MPH, PHD; YAZAN A. AL-AJLOUNI, MPHIL
In the dynamic realm of medicine, artificial intelligence (AI) emerges as a transformative force, notably within hepatology. The discipline of hepatology, dedicated to liver and related organ diseases, is ripe for AI’s promise to revolutionize diagnostics and treatment, pushing toward a future of precision medicine. Yet, the path to fully realizing AI’s potential in hepatology is laced with data, ethical, and integration challenges.
The application of AI, particularly in histopathology, significantly enhances disease diagnosis and staging in hepatology. AI-driven approaches remedy traditional histopathological challenges, such as interpretative variability, providing more consistent and accurate disease analyses. This is especially evident in conditions like metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), where AI aids in identifying critical gene signatures, thereby refining therapy selection.
Similarly, deep learning (DL), a branch of AI, has attracted significant interest globally, particularly in image recognition. AI’s incorporation into medical imaging marks a significant advancement, enabling early detection of malignancies like HCC and improving diagnostics in steatotic liver disease through enhanced imaging analyses using convolutional neural networks (CNN). The abundance of imaging data alongside clinical outcomes has catalyzed AI’s integration into radiology, leading to the swift growth of radiomics as a novel domain in medical research.
AI has also been shown to identify nuanced alterations in electrocardiograms (EKGs) associated with liver conditions, potentially detecting the progression of liver diseases at an earlier stage than currently possible. By leveraging complex algorithms and machine learning, AI can analyze EKG patterns with a precision and depth unattainable through traditional manual interpretation. Given that liver diseases, such as cirrhosis or hepatitis, can induce subtle cardiac changes long before other clinical symptoms manifest, early detection through AI-enhanced EKG analysis could lead to timely interventions, potentially halting or reversing disease progression. This approach further enriches our understanding of the intricate interplay between liver function and cardiac health, highlighting the potential for AI to transform not just liver disease diagnostics but also to foster a more integrated approach to patient care.
Beyond diagnostics, the burgeoning field of generative AI introduces groundbreaking possibilities in treatment planning and patient education, particularly for chronic conditions like cirrhosis. Generative AI produces original content, including text, visuals, and music, by identifying and learning patterns from its training data. When it leverages large language models (LLMs), it entails training on vast collections of textual data and using AI models characterized by many parameters. A notable instance of generative AI employing LLMs is ChatGPT (General Pretrained Transformers). By simulating disease progression and treatment outcomes, generative AI can foster personalized treatment strategies and empower patients with knowledge about their health trajectories. Yet, realizing these potential demands requires overcoming data quality and interpretability challenges, and ensuring AI outputs are accessible and actionable for clinicians and patients.
Despite these advancements, leveraging AI in hepatology is not devoid of hurdles. The development and training of AI models require extensive and diverse datasets, raising concerns about data privacy and ethical use. Addressing these concerns is paramount for successfully integrating AI into clinical hepatology practice, necessitating transparent algorithmic processes and stringent ethical standards. Ethical considerations are central to AI’s integration into hepatology. Algorithmic biases, patient privacy, and the impact of AI-driven decisions underscore the need for cautious AI deployment. Developing transparent, understandable algorithms and establishing ethical guidelines for AI use are critical steps towards ethically leveraging AI in patient care.
In conclusion, AI’s integration into hepatology holds tremendous promise for advancing patient care through enhanced diagnostics, treatment planning, and patient education. Overcoming the associated challenges, including ethical concerns, data diversity, and algorithm interpretability, is crucial. As the hepatology community navigates this technological evolution, a balanced approach that marries technological advancements with ethical stewardship will be key to harnessing AI’s full potential, ensuring it serves the best interests of patients and propels the field of hepatology into the future.
We predict a trajectory of increased use and adoption of AI in hepatology. AI in hepatology is likely to meet the test of pervasiveness, improvement, and innovation. The adoption of AI in routine hepatology diagnosis and management will likely follow Amara’s law and the five stages of the hype cycle. We believe that we are still in the infant stages of adopting AI technology in hepatology, and this phase may last 5 years before there is a peak of inflated expectations. The trough of disillusionment and slopes of enlightenment may only be observed in the next decades.
Dr. Njei is based in the Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn. Mr. Al-Ajlouni is a senior medical student at New York Medical College School of Medicine, Valhalla, N.Y. They have no conflicts of interest to declare.
Sources
Taylor-Weiner A, et al. A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH. Hepatology. 2021 Jul. doi: 10.1002/hep.31750.
Zeng Q, et al. Artificial intelligence predicts immune and inflammatory gene signatures directly from hepatocellular carcinoma histology. J Hepatol. 2022 Jul. doi: 10.1016/j.jhep.2022.01.018.
Ahn JC, et al. Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis. Am J Gastroenterol. 2022 Mar. doi: 10.14309/ajg.0000000000001617.
Nduma BN, et al. The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review. Cureus. 2023 Dec 15. doi: 10.7759/cureus.50601.
Dear colleagues,
Since our prior Perspectives piece on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. Expectations are high that AI will revolutionize our field and significantly improve patient care. But as the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.
In this issue, Dr. Nabil M. Mansour and Dr. Thomas R. McCarty explore the current and future impact of AI on gastroenterology, while Dr. Basile Njei and Yazan A. Al Ajlouni assess its role in hepatology. We hope these pieces will help your discussions in incorporating or researching AI for use in your own practices. We welcome your thoughts on this issue on X @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.
Artificial Intelligence in Gastrointestinal Endoscopy
BY THOMAS R. MCCARTY, MD, MPH; NABIL M. MANSOUR, MD
The last few decades have seen an exponential increase and interest in the role of artificial intelligence (AI) and adoption of deep learning algorithms within healthcare and patient care services. The field of gastroenterology and endoscopy has similarly seen a tremendous uptake in acceptance and implementation of AI for a variety of gastrointestinal conditions. The spectrum of AI-based applications includes detection or diagnostic-based as well as therapeutic assistance tools. From the first US Food and Drug Administration (FDA)-approved device that uses machine learning to assist clinicians in detecting lesions during colonoscopy, to other more innovative machine learning techniques for small bowel, esophageal, and hepatobiliary conditions, AI has dramatically changed the landscape of gastrointestinal endoscopy.
Approved applications for colorectal cancer
In an attempt to improve colorectal cancer screening and outcomes related to screening and surveillance, efforts have been focused on procedural performance metrics, quality indicators, and tools to aid in lesion detection and improve quality of care. One such tool has been computer-aided detection (CADe), with early randomized controlled trial (RCT) data showing significantly increased adenoma detection rate (ADR) and adenomas per colonoscopy (APC).1-3
Ultimately, this data led to FDA approval of the CADe system GI Genius (Medtronic, Dublin, Ireland) in 2021.4 Additional systems have since been FDA approved or 510(k) cleared including Endoscreener (Wision AI, Shanghai, China), SKOUT (Iterative Health, Cambridge, Massachusetts), MAGENTIQ-COLO (MAGENTIQ-EYE LTD, Haifa, Israel), and CAD EYE (Fujifilm, Tokyo), all of which have shown increased ADR and/or increased APC and/or reduced adenoma miss rates in randomized trials.5
Yet despite the promise of improved quality and subsequent translation to better patient outcomes, there has been a noticeable disconnect between RCT data and more real-world literature.6 In a recent study, no improvement was seen in ADR after implementation of a CADe system for colorectal cancer screening — including both higher and lower-ADR performers. Looking at change over time after implementation, CADe had no positive effect in any group over time, divergent from early RCT data. In a more recent multicenter, community-based RCT study, again CADe did not result in a statistically significant difference in the number of adenomas detected.7 The differences between some of these more recent “real-world” studies vs the majority of data from RCTs raise important questions regarding the potential of bias (due to unblinding) in prospective trials, as well as the role of the human-AI interaction.
Importantly for RCT data, both cohorts in these studies met adequate ADR benchmarks, though it remains unclear whether a truly increased ADR necessitates better patient outcomes — is higher always better? In addition, an important consideration with evaluating any AI/CADe system is that they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using an outdated version of a CADe system.
Additional unanswered questions regarding an ideal ADR for implementation, preferred patient populations for screening (especially for younger individuals), and the role and adoption of computer-aided polyp diagnosis/characterization (CADx) within the United States remain. Furthermore, questions regarding procedural withdrawal time, impact on sessile serrated lesion detection, cost-effectiveness, and preferred adoption strategies have begun to be explored, though require more data to better define a best practice approach. Ultimately, answers to some of these unknowns may explain the discordant results and help guide future implementation measures.
Innovative applications for alternative gastrointestinal conditions
Given the fervor and excitement, as well as the outcomes associated with AI-based colorectal screening, it is not surprising these techniques have been expanded to other gastrointestinal conditions. At this time, all of these are fledgling, mostly single-center tools, not yet ready for widespread adoption. Nonetheless, these represent a potentially important step forward for difficult-to-manage gastrointestinal diseases.
Machine learning CADe systems have been developed to help identify early Barrett’s neoplasia, depth and invasion of gastric cancer, as well as lesion detection in small bowel video capsule endoscopy.8-10 Endoscopic retrograde cholangiopancreatography (ERCP)-based applications for cholangiocarcinoma and indeterminate stricture diagnosis have also been studied.11 Additional AI-based algorithms have been employed for complex procedures such as endoscopic submucosal dissection (ESD) or peroral endoscopic myotomy (POEM) to delineate vessels, better define tissue planes for dissection, and visualize landmark structures.12,13 Furthermore, AI-based scope guidance/manipulation, bleeding detection, landmark identification, and lesion detection have the potential to revolutionize endoscopic training and education. The impact that generative AI can potentially have on clinical practice is also an exciting prospect that warrants further investigation.
Artificial intelligence adoption in clinical practice
Clinical practice with regard to AI and colorectal cancer screening largely mirrors the disconnect in the current literature, with “believers” and “non-believers” as well as innovators and early adopters alongside laggards. In our own academic practices, we continue to struggle with the adoption and standardized implementation of AI-based colorectal cancer CADe systems, despite the RCT data showing positive results. It is likely that AI uptake will follow the technology predictions of Amara’s Law — i.e., individuals tend to overestimate the short-term impact of new technologies while underestimating long-term effects. In the end, more widespread adoption in community practice and larger scale real-world clinical outcomes studies are likely to determine the true impact of these exciting technologies. For other, less established AI-based tools, more data are currently required.
Conclusions
Ultimately, AI-based algorithms are likely here to stay, with continued improvement and evolution to occur based on provider feedback and patient care needs. Current tools, while not all-encompassing, have the potential to dramatically change the landscape of endoscopic training, diagnostic evaluation, and therapeutic care. It is critically important that relevant stakeholders, both endoscopists and patients, be involved in future applications and design to improve efficiency and quality outcomes overall.
Dr. McCarty is based in the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital. Dr. Mansour is based in the section of gastroenterology, Baylor College of Medicine, Houston. Dr. McCarty reports no conflicts of interest. Dr. Mansour reports having been a consultant for Iterative Health.
References
1. Repici A, et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology. 2020 Aug. doi: 10.1053/j.gastro.2020.04.062.
2. Repici A, et al. Artificial intelligence and colonoscopy experience: Lessons from two randomised trials. Gut. Apr 2022. doi: 10.1136/gutjnl-2021-324471.
3. Wallace MB, et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology 2022 Jul. doi: 10.1053/j.gastro.2022.03.007.
4. United States Food and Drug Administration (FDA). GI Genius FDA Approval [April 9, 2021]. Accessed January 5, 2022. Available at: www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf.
5. Maas MHJ, et al. A computer-aided polyp detection system in screening and surveillance colonoscopy: An international, multicentre, randomised, tandem trial. Lancet Digit Health. 2024 Mar. doi: 10.1016/S2589-7500(23)00242-X.
6. Ladabaum U, et al. Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology. 2023 Mar. doi: 10.1053/j.gastro.2022.12.004.
7. Wei MT, et al. Evaluation of computer-aided detection during colonoscopy in the community (AI-SEE): A multicenter randomized clinical trial. Am J Gastroenterol. 2023 Oct. doi: 10.14309/ajg.0000000000002239.
8. de Groof J, et al. The Argos project: The development of a computer-aided detection system to improve detection of Barrett’s neoplasia on white light endoscopy. United European Gastroenterol J. 2019 May. doi: 10.1177/2050640619837443.
9. Kanesaka T, et al. Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging. Gastrointest Endosc. 2018 May. doi: 10.1016/j.gie.2017.11.029.
10. Sahafi A, et al. Edge artificial intelligence wireless video capsule endoscopy. Sci Rep. 2022 Aug. doi: 10.1038/s41598-022-17502-7.
11. Njei B, et al. Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: A systematic review. Ann Gastroenterol. 2023 Mar-Apr. doi: 10.20524/aog.2023.0779.
12. Ebigbo A, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut. 2022 Dec. doi: 10.1136/gutjnl-2021-326470.
13. Cao J, et al. Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study. Nat Commun. 2023 Oct. doi: 10.1038/s41467-023-42451-8.
The Promise and Challenges of AI in Hepatology
BY BASILE NJEI, MD, MPH, PHD; YAZAN A. AL-AJLOUNI, MPHIL
In the dynamic realm of medicine, artificial intelligence (AI) emerges as a transformative force, notably within hepatology. The discipline of hepatology, dedicated to liver and related organ diseases, is ripe for AI’s promise to revolutionize diagnostics and treatment, pushing toward a future of precision medicine. Yet, the path to fully realizing AI’s potential in hepatology is laced with data, ethical, and integration challenges.
The application of AI, particularly in histopathology, significantly enhances disease diagnosis and staging in hepatology. AI-driven approaches remedy traditional histopathological challenges, such as interpretative variability, providing more consistent and accurate disease analyses. This is especially evident in conditions like metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), where AI aids in identifying critical gene signatures, thereby refining therapy selection.
Similarly, deep learning (DL), a branch of AI, has attracted significant interest globally, particularly in image recognition. AI’s incorporation into medical imaging marks a significant advancement, enabling early detection of malignancies like HCC and improving diagnostics in steatotic liver disease through enhanced imaging analyses using convolutional neural networks (CNN). The abundance of imaging data alongside clinical outcomes has catalyzed AI’s integration into radiology, leading to the swift growth of radiomics as a novel domain in medical research.
AI has also been shown to identify nuanced alterations in electrocardiograms (EKGs) associated with liver conditions, potentially detecting the progression of liver diseases at an earlier stage than currently possible. By leveraging complex algorithms and machine learning, AI can analyze EKG patterns with a precision and depth unattainable through traditional manual interpretation. Given that liver diseases, such as cirrhosis or hepatitis, can induce subtle cardiac changes long before other clinical symptoms manifest, early detection through AI-enhanced EKG analysis could lead to timely interventions, potentially halting or reversing disease progression. This approach further enriches our understanding of the intricate interplay between liver function and cardiac health, highlighting the potential for AI to transform not just liver disease diagnostics but also to foster a more integrated approach to patient care.
Beyond diagnostics, the burgeoning field of generative AI introduces groundbreaking possibilities in treatment planning and patient education, particularly for chronic conditions like cirrhosis. Generative AI produces original content, including text, visuals, and music, by identifying and learning patterns from its training data. When it leverages large language models (LLMs), it entails training on vast collections of textual data and using AI models characterized by many parameters. A notable instance of generative AI employing LLMs is ChatGPT (General Pretrained Transformers). By simulating disease progression and treatment outcomes, generative AI can foster personalized treatment strategies and empower patients with knowledge about their health trajectories. Yet, realizing these potential demands requires overcoming data quality and interpretability challenges, and ensuring AI outputs are accessible and actionable for clinicians and patients.
Despite these advancements, leveraging AI in hepatology is not devoid of hurdles. The development and training of AI models require extensive and diverse datasets, raising concerns about data privacy and ethical use. Addressing these concerns is paramount for successfully integrating AI into clinical hepatology practice, necessitating transparent algorithmic processes and stringent ethical standards. Ethical considerations are central to AI’s integration into hepatology. Algorithmic biases, patient privacy, and the impact of AI-driven decisions underscore the need for cautious AI deployment. Developing transparent, understandable algorithms and establishing ethical guidelines for AI use are critical steps towards ethically leveraging AI in patient care.
In conclusion, AI’s integration into hepatology holds tremendous promise for advancing patient care through enhanced diagnostics, treatment planning, and patient education. Overcoming the associated challenges, including ethical concerns, data diversity, and algorithm interpretability, is crucial. As the hepatology community navigates this technological evolution, a balanced approach that marries technological advancements with ethical stewardship will be key to harnessing AI’s full potential, ensuring it serves the best interests of patients and propels the field of hepatology into the future.
We predict a trajectory of increased use and adoption of AI in hepatology. AI in hepatology is likely to meet the test of pervasiveness, improvement, and innovation. The adoption of AI in routine hepatology diagnosis and management will likely follow Amara’s law and the five stages of the hype cycle. We believe that we are still in the infant stages of adopting AI technology in hepatology, and this phase may last 5 years before there is a peak of inflated expectations. The trough of disillusionment and slopes of enlightenment may only be observed in the next decades.
Dr. Njei is based in the Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn. Mr. Al-Ajlouni is a senior medical student at New York Medical College School of Medicine, Valhalla, N.Y. They have no conflicts of interest to declare.
Sources
Taylor-Weiner A, et al. A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH. Hepatology. 2021 Jul. doi: 10.1002/hep.31750.
Zeng Q, et al. Artificial intelligence predicts immune and inflammatory gene signatures directly from hepatocellular carcinoma histology. J Hepatol. 2022 Jul. doi: 10.1016/j.jhep.2022.01.018.
Ahn JC, et al. Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis. Am J Gastroenterol. 2022 Mar. doi: 10.14309/ajg.0000000000001617.
Nduma BN, et al. The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review. Cureus. 2023 Dec 15. doi: 10.7759/cureus.50601.
Navigating the Search for a Financial Adviser
As gastroenterologists, we spend innumerable years in medical training with an abrupt and significant increase in our earning potential upon beginning practice. The majority of us also carry a sizeable amount of student loan debt. This combination results in a unique situation that can make us hesitant about how best to set ourselves up financially while also making us vulnerable to potentially predatory financial practices.
Although your initial steps to achieve financial wellness and build wealth can be obtained on your own with some education, a financial adviser becomes indispensable when you have significant assets, a high income, complex finances, and/or are experiencing a major life change. Additionally, as there are so many avenues to invest and grow your capital, a financial adviser can assist in designing a portfolio to best accomplish specific monetary goals. Studies have demonstrated that those working with a financial adviser reduce their single-stock risk and have more significant increase in portfolio value, reducing the total cost associated with their investments’ management.1 Those working with a financial adviser will also net up to a 3% larger annual return, compared with a standard baseline investment plan.2,3
Based on this information, it may appear that working with a personal financial adviser would be a no-brainer. Unfortunately, there is a caveat: There is no legal regulation regarding who can use the title “financial adviser.” It is therefore crucial to be aware of common practices and terminology to best help you identify a reputable financial adviser and reduce your risk of excessive fees or financial loss. This is also a highly personal decision and your search should first begin with understanding why you are looking for an adviser, as this will determine the appropriate type of service to look for.
Types of Advisers
A certified financial planner (CFP) is an expert in estate planning, taxes, retirement saving, and financial planning who has a formal designation by the Certified Financial Planner Board of Standards Inc.4 They must undergo stringent licensing examinations following a 3-year course with required continuing education to maintain their credentials. CFPs are fiduciaries, meaning they must make financial decisions in your best interest, even if they may make less money with that product or investment strategy. In other words, they are beholden to give honest, impartial recommendations to their clients, and may face sanctions by the CFP Board if found to violate its Code of Ethics and Standards of Conduct, which includes failure to act in a fiduciary duty.5
CFPs evaluate your total financial picture, such as investments, insurance policies, and overall current financial position, to develop a comprehensive strategy that will successfully guide you to your financial goal. There are many individuals who may refer to themselves as financial planners without having the CFP designation; while they may offer similar services as above, they will not be required to act as a fiduciary. Hence, it is important to do your due diligence and verify they hold this certification via the CFP Board website: www.cfp.net/verify-a-cfp-professional.
An investment adviser is a legal term from the U.S. Securities and Exchange Commission (SEC) and the Financial Industry Regulatory Authority (FINRA) referring to an individual who provides recommendations and analyses for financial securities such as stock. Both of these agencies ensure investment advisers adhere to regulatory requirements designed to protect client investers. Similar to CFPs, they are held to a fiduciary standard, and their firm is required to register with the SEC or the state of practice based on the amount of assets under management.6
An individual investment adviser must also register with their state as an Investment Adviser Representative (IAR), the distinctive term referring to an individual as opposed to an investment advising firm. Investment advisers are required to pass the extensive Series 65, Uniform Investment Advisor Law Exam, or equivalent, by states requiring licensure.7 They can guide you on the selection of particular investments and portfolio management based on a discussion with you regarding your current financial standing and what fiscal ambitions you wish to achieve.
A financial adviser provides direction on a multitude of financially related topics such as investing, tax laws, and life insurance with the goal to help you reach specific financial objectives. However, this term is often used quite ubiquitously given the lack of formal regulation of the title. Essentially, those with varying types of educational background can give themselves the title of financial adviser.
If a financial adviser buys or sells financial securities such as stocks or bonds, then they must be registered as a licensed broker with the SEC and IAR and pass the Series 6 or Series 7 exam. Unlike CFPs and investment advisers, a financial adviser (if also a licensed broker) is not required to be a fiduciary, and instead works under the suitability standard.8 Suitability requires that financial recommendations made by the adviser are appropriate but not necessarily the best for the client. In fact, these recommendations do not even have to be the most suitable. This is where conflicts of interest can arise with the adviser recommending products and securities that best compensate them while not serving the best return on investment for you.
Making the search for a financial adviser more complex, an individual can be a combination of any of the above, pending the appropriate licensing. For example, a CFP can also be an asset manager and thus hold the title of a financial adviser and/or IAR. A financial adviser may also not directly manage your assets if they have a partnership with a third party or another licensed individual. Questions to ask of your potential financial adviser should therefore include the following:
- What licensure and related education do you have?
- What is your particular area of expertise?
- How long have you been in practice?
- How will you be managing my assets?
Financial Adviser Fee Schedules
Prior to working with a financial adviser, you must also inquire about their fee structure. There are two kinds of fee schedules used by financial advisers: fee-only and fee-based.
Fee-only advisers receive payment solely for the services they provide. They do not collect commissions from third parties providing the recommended products. There is variability in how this type of payment schedule is structured, encompassing flat fees, hourly rates, or the adviser charging a retainer. The Table below compares the types of fee-only structures and range of charges based on 2023 rates.9 Of note, fee-only advisers serve as fiduciaries.10
Fee-based financial advisers receive payment for services but may also receive commission on specific products they sell to you.9 Most, if not all, financial experts recommend avoiding advisers using commission-based charges given the potential conflict of interest: How can one be absolutely sure this recommended financial product is best for you, knowing your adviser has a financial stake in said item?
In addition to charging the fees above, your financial adviser, if they are actively managing your investment portfolio, will also charge an assets under management (AUM) fee. This is a percentage of the dollar amount within your portfolio. For example, if your adviser charges a 1% AUM rate for your account totaling $100,000, this equates to a $1,000 fee in that calendar year. AUM fees typically decrease as the size of your portfolio increases. As seen in the Table, there is a wide range of the average AUM rate (0.5%–2%); however, an AUM fee approaching 2% is unnecessarily high and consumes a significant portion of your portfolio. Thus, it is recommended to look for a money manager with an approximate 1% AUM fee.
Many of us delay or avoid working with a financial adviser due to the potential perceived risks of having poor portfolio management from an adviser not working in our best interest, along with the concern for excessive fees. In many ways, it is how we counsel our patients. While they can seek medical information on their own, their best care is under the guidance of an expert: a healthcare professional. That being said, personal finance is indeed personal, so I hope this guide helps facilitate your search and increase your financial wellness.
Dr. Luthra is a therapeutic endoscopist at Moffitt Cancer Center, Tampa, Florida, and the founder of The Scope of Finance, a financial wellness education and coaching company focused on physicians. Her interest in financial well-being is thanks to the teachings of her father, an entrepreneur and former Certified Financial Planner (CFP). She can be found on Instagram (thescopeoffinance) and X (@ScopeofFinance). She reports no financial disclosures relevant to this article.
References
1. Pagliaro CA and Utkus SP. Assessing the value of advice. Vanguard. 2019 Sept.
2. Kinniry Jr. FM et al. Putting a value on your value: Quantifying Vanguard Advisor’s Alpha. Vanguard. 2022 July.
3. Horan S. What Are the Benefits of Working with a Financial Advisor? – 2021 Study. Smart Asset. 2023 July 27.
4. Kagan J. Certified Financial PlannerTM(CFP): What It Is and How to Become One. Investopedia. 2023 Aug 3.
5. CFP Board. Our Commitment to Ethical Standards. CFP Board. 2024.
6. Staff of the Investment Adviser Regulation Office Division of Investment Management, U.S. Securities and Exchange Commission. Regulation of Investment Advisers by the U.S. Securities and Exchange Commission. 2013 Mar.
7. Hicks C. Investment Advisor vs. Financial Advisor: There is a Difference. US News & World Report. 2019 June 13.
8. Roberts K. Financial advisor vs. financial planner: What is the difference? Bankrate. 2023 Nov 21.
9. Clancy D. Average Fees for Financial Advisors in 2023. Harness Wealth. 2023 May 25.
10. Palmer B. Fee- vs. Commission-Based Advisor: What’s the Difference? Investopedia. 2023 June 20.
As gastroenterologists, we spend innumerable years in medical training with an abrupt and significant increase in our earning potential upon beginning practice. The majority of us also carry a sizeable amount of student loan debt. This combination results in a unique situation that can make us hesitant about how best to set ourselves up financially while also making us vulnerable to potentially predatory financial practices.
Although your initial steps to achieve financial wellness and build wealth can be obtained on your own with some education, a financial adviser becomes indispensable when you have significant assets, a high income, complex finances, and/or are experiencing a major life change. Additionally, as there are so many avenues to invest and grow your capital, a financial adviser can assist in designing a portfolio to best accomplish specific monetary goals. Studies have demonstrated that those working with a financial adviser reduce their single-stock risk and have more significant increase in portfolio value, reducing the total cost associated with their investments’ management.1 Those working with a financial adviser will also net up to a 3% larger annual return, compared with a standard baseline investment plan.2,3
Based on this information, it may appear that working with a personal financial adviser would be a no-brainer. Unfortunately, there is a caveat: There is no legal regulation regarding who can use the title “financial adviser.” It is therefore crucial to be aware of common practices and terminology to best help you identify a reputable financial adviser and reduce your risk of excessive fees or financial loss. This is also a highly personal decision and your search should first begin with understanding why you are looking for an adviser, as this will determine the appropriate type of service to look for.
Types of Advisers
A certified financial planner (CFP) is an expert in estate planning, taxes, retirement saving, and financial planning who has a formal designation by the Certified Financial Planner Board of Standards Inc.4 They must undergo stringent licensing examinations following a 3-year course with required continuing education to maintain their credentials. CFPs are fiduciaries, meaning they must make financial decisions in your best interest, even if they may make less money with that product or investment strategy. In other words, they are beholden to give honest, impartial recommendations to their clients, and may face sanctions by the CFP Board if found to violate its Code of Ethics and Standards of Conduct, which includes failure to act in a fiduciary duty.5
CFPs evaluate your total financial picture, such as investments, insurance policies, and overall current financial position, to develop a comprehensive strategy that will successfully guide you to your financial goal. There are many individuals who may refer to themselves as financial planners without having the CFP designation; while they may offer similar services as above, they will not be required to act as a fiduciary. Hence, it is important to do your due diligence and verify they hold this certification via the CFP Board website: www.cfp.net/verify-a-cfp-professional.
An investment adviser is a legal term from the U.S. Securities and Exchange Commission (SEC) and the Financial Industry Regulatory Authority (FINRA) referring to an individual who provides recommendations and analyses for financial securities such as stock. Both of these agencies ensure investment advisers adhere to regulatory requirements designed to protect client investers. Similar to CFPs, they are held to a fiduciary standard, and their firm is required to register with the SEC or the state of practice based on the amount of assets under management.6
An individual investment adviser must also register with their state as an Investment Adviser Representative (IAR), the distinctive term referring to an individual as opposed to an investment advising firm. Investment advisers are required to pass the extensive Series 65, Uniform Investment Advisor Law Exam, or equivalent, by states requiring licensure.7 They can guide you on the selection of particular investments and portfolio management based on a discussion with you regarding your current financial standing and what fiscal ambitions you wish to achieve.
A financial adviser provides direction on a multitude of financially related topics such as investing, tax laws, and life insurance with the goal to help you reach specific financial objectives. However, this term is often used quite ubiquitously given the lack of formal regulation of the title. Essentially, those with varying types of educational background can give themselves the title of financial adviser.
If a financial adviser buys or sells financial securities such as stocks or bonds, then they must be registered as a licensed broker with the SEC and IAR and pass the Series 6 or Series 7 exam. Unlike CFPs and investment advisers, a financial adviser (if also a licensed broker) is not required to be a fiduciary, and instead works under the suitability standard.8 Suitability requires that financial recommendations made by the adviser are appropriate but not necessarily the best for the client. In fact, these recommendations do not even have to be the most suitable. This is where conflicts of interest can arise with the adviser recommending products and securities that best compensate them while not serving the best return on investment for you.
Making the search for a financial adviser more complex, an individual can be a combination of any of the above, pending the appropriate licensing. For example, a CFP can also be an asset manager and thus hold the title of a financial adviser and/or IAR. A financial adviser may also not directly manage your assets if they have a partnership with a third party or another licensed individual. Questions to ask of your potential financial adviser should therefore include the following:
- What licensure and related education do you have?
- What is your particular area of expertise?
- How long have you been in practice?
- How will you be managing my assets?
Financial Adviser Fee Schedules
Prior to working with a financial adviser, you must also inquire about their fee structure. There are two kinds of fee schedules used by financial advisers: fee-only and fee-based.
Fee-only advisers receive payment solely for the services they provide. They do not collect commissions from third parties providing the recommended products. There is variability in how this type of payment schedule is structured, encompassing flat fees, hourly rates, or the adviser charging a retainer. The Table below compares the types of fee-only structures and range of charges based on 2023 rates.9 Of note, fee-only advisers serve as fiduciaries.10
Fee-based financial advisers receive payment for services but may also receive commission on specific products they sell to you.9 Most, if not all, financial experts recommend avoiding advisers using commission-based charges given the potential conflict of interest: How can one be absolutely sure this recommended financial product is best for you, knowing your adviser has a financial stake in said item?
In addition to charging the fees above, your financial adviser, if they are actively managing your investment portfolio, will also charge an assets under management (AUM) fee. This is a percentage of the dollar amount within your portfolio. For example, if your adviser charges a 1% AUM rate for your account totaling $100,000, this equates to a $1,000 fee in that calendar year. AUM fees typically decrease as the size of your portfolio increases. As seen in the Table, there is a wide range of the average AUM rate (0.5%–2%); however, an AUM fee approaching 2% is unnecessarily high and consumes a significant portion of your portfolio. Thus, it is recommended to look for a money manager with an approximate 1% AUM fee.
Many of us delay or avoid working with a financial adviser due to the potential perceived risks of having poor portfolio management from an adviser not working in our best interest, along with the concern for excessive fees. In many ways, it is how we counsel our patients. While they can seek medical information on their own, their best care is under the guidance of an expert: a healthcare professional. That being said, personal finance is indeed personal, so I hope this guide helps facilitate your search and increase your financial wellness.
Dr. Luthra is a therapeutic endoscopist at Moffitt Cancer Center, Tampa, Florida, and the founder of The Scope of Finance, a financial wellness education and coaching company focused on physicians. Her interest in financial well-being is thanks to the teachings of her father, an entrepreneur and former Certified Financial Planner (CFP). She can be found on Instagram (thescopeoffinance) and X (@ScopeofFinance). She reports no financial disclosures relevant to this article.
References
1. Pagliaro CA and Utkus SP. Assessing the value of advice. Vanguard. 2019 Sept.
2. Kinniry Jr. FM et al. Putting a value on your value: Quantifying Vanguard Advisor’s Alpha. Vanguard. 2022 July.
3. Horan S. What Are the Benefits of Working with a Financial Advisor? – 2021 Study. Smart Asset. 2023 July 27.
4. Kagan J. Certified Financial PlannerTM(CFP): What It Is and How to Become One. Investopedia. 2023 Aug 3.
5. CFP Board. Our Commitment to Ethical Standards. CFP Board. 2024.
6. Staff of the Investment Adviser Regulation Office Division of Investment Management, U.S. Securities and Exchange Commission. Regulation of Investment Advisers by the U.S. Securities and Exchange Commission. 2013 Mar.
7. Hicks C. Investment Advisor vs. Financial Advisor: There is a Difference. US News & World Report. 2019 June 13.
8. Roberts K. Financial advisor vs. financial planner: What is the difference? Bankrate. 2023 Nov 21.
9. Clancy D. Average Fees for Financial Advisors in 2023. Harness Wealth. 2023 May 25.
10. Palmer B. Fee- vs. Commission-Based Advisor: What’s the Difference? Investopedia. 2023 June 20.
As gastroenterologists, we spend innumerable years in medical training with an abrupt and significant increase in our earning potential upon beginning practice. The majority of us also carry a sizeable amount of student loan debt. This combination results in a unique situation that can make us hesitant about how best to set ourselves up financially while also making us vulnerable to potentially predatory financial practices.
Although your initial steps to achieve financial wellness and build wealth can be obtained on your own with some education, a financial adviser becomes indispensable when you have significant assets, a high income, complex finances, and/or are experiencing a major life change. Additionally, as there are so many avenues to invest and grow your capital, a financial adviser can assist in designing a portfolio to best accomplish specific monetary goals. Studies have demonstrated that those working with a financial adviser reduce their single-stock risk and have more significant increase in portfolio value, reducing the total cost associated with their investments’ management.1 Those working with a financial adviser will also net up to a 3% larger annual return, compared with a standard baseline investment plan.2,3
Based on this information, it may appear that working with a personal financial adviser would be a no-brainer. Unfortunately, there is a caveat: There is no legal regulation regarding who can use the title “financial adviser.” It is therefore crucial to be aware of common practices and terminology to best help you identify a reputable financial adviser and reduce your risk of excessive fees or financial loss. This is also a highly personal decision and your search should first begin with understanding why you are looking for an adviser, as this will determine the appropriate type of service to look for.
Types of Advisers
A certified financial planner (CFP) is an expert in estate planning, taxes, retirement saving, and financial planning who has a formal designation by the Certified Financial Planner Board of Standards Inc.4 They must undergo stringent licensing examinations following a 3-year course with required continuing education to maintain their credentials. CFPs are fiduciaries, meaning they must make financial decisions in your best interest, even if they may make less money with that product or investment strategy. In other words, they are beholden to give honest, impartial recommendations to their clients, and may face sanctions by the CFP Board if found to violate its Code of Ethics and Standards of Conduct, which includes failure to act in a fiduciary duty.5
CFPs evaluate your total financial picture, such as investments, insurance policies, and overall current financial position, to develop a comprehensive strategy that will successfully guide you to your financial goal. There are many individuals who may refer to themselves as financial planners without having the CFP designation; while they may offer similar services as above, they will not be required to act as a fiduciary. Hence, it is important to do your due diligence and verify they hold this certification via the CFP Board website: www.cfp.net/verify-a-cfp-professional.
An investment adviser is a legal term from the U.S. Securities and Exchange Commission (SEC) and the Financial Industry Regulatory Authority (FINRA) referring to an individual who provides recommendations and analyses for financial securities such as stock. Both of these agencies ensure investment advisers adhere to regulatory requirements designed to protect client investers. Similar to CFPs, they are held to a fiduciary standard, and their firm is required to register with the SEC or the state of practice based on the amount of assets under management.6
An individual investment adviser must also register with their state as an Investment Adviser Representative (IAR), the distinctive term referring to an individual as opposed to an investment advising firm. Investment advisers are required to pass the extensive Series 65, Uniform Investment Advisor Law Exam, or equivalent, by states requiring licensure.7 They can guide you on the selection of particular investments and portfolio management based on a discussion with you regarding your current financial standing and what fiscal ambitions you wish to achieve.
A financial adviser provides direction on a multitude of financially related topics such as investing, tax laws, and life insurance with the goal to help you reach specific financial objectives. However, this term is often used quite ubiquitously given the lack of formal regulation of the title. Essentially, those with varying types of educational background can give themselves the title of financial adviser.
If a financial adviser buys or sells financial securities such as stocks or bonds, then they must be registered as a licensed broker with the SEC and IAR and pass the Series 6 or Series 7 exam. Unlike CFPs and investment advisers, a financial adviser (if also a licensed broker) is not required to be a fiduciary, and instead works under the suitability standard.8 Suitability requires that financial recommendations made by the adviser are appropriate but not necessarily the best for the client. In fact, these recommendations do not even have to be the most suitable. This is where conflicts of interest can arise with the adviser recommending products and securities that best compensate them while not serving the best return on investment for you.
Making the search for a financial adviser more complex, an individual can be a combination of any of the above, pending the appropriate licensing. For example, a CFP can also be an asset manager and thus hold the title of a financial adviser and/or IAR. A financial adviser may also not directly manage your assets if they have a partnership with a third party or another licensed individual. Questions to ask of your potential financial adviser should therefore include the following:
- What licensure and related education do you have?
- What is your particular area of expertise?
- How long have you been in practice?
- How will you be managing my assets?
Financial Adviser Fee Schedules
Prior to working with a financial adviser, you must also inquire about their fee structure. There are two kinds of fee schedules used by financial advisers: fee-only and fee-based.
Fee-only advisers receive payment solely for the services they provide. They do not collect commissions from third parties providing the recommended products. There is variability in how this type of payment schedule is structured, encompassing flat fees, hourly rates, or the adviser charging a retainer. The Table below compares the types of fee-only structures and range of charges based on 2023 rates.9 Of note, fee-only advisers serve as fiduciaries.10
Fee-based financial advisers receive payment for services but may also receive commission on specific products they sell to you.9 Most, if not all, financial experts recommend avoiding advisers using commission-based charges given the potential conflict of interest: How can one be absolutely sure this recommended financial product is best for you, knowing your adviser has a financial stake in said item?
In addition to charging the fees above, your financial adviser, if they are actively managing your investment portfolio, will also charge an assets under management (AUM) fee. This is a percentage of the dollar amount within your portfolio. For example, if your adviser charges a 1% AUM rate for your account totaling $100,000, this equates to a $1,000 fee in that calendar year. AUM fees typically decrease as the size of your portfolio increases. As seen in the Table, there is a wide range of the average AUM rate (0.5%–2%); however, an AUM fee approaching 2% is unnecessarily high and consumes a significant portion of your portfolio. Thus, it is recommended to look for a money manager with an approximate 1% AUM fee.
Many of us delay or avoid working with a financial adviser due to the potential perceived risks of having poor portfolio management from an adviser not working in our best interest, along with the concern for excessive fees. In many ways, it is how we counsel our patients. While they can seek medical information on their own, their best care is under the guidance of an expert: a healthcare professional. That being said, personal finance is indeed personal, so I hope this guide helps facilitate your search and increase your financial wellness.
Dr. Luthra is a therapeutic endoscopist at Moffitt Cancer Center, Tampa, Florida, and the founder of The Scope of Finance, a financial wellness education and coaching company focused on physicians. Her interest in financial well-being is thanks to the teachings of her father, an entrepreneur and former Certified Financial Planner (CFP). She can be found on Instagram (thescopeoffinance) and X (@ScopeofFinance). She reports no financial disclosures relevant to this article.
References
1. Pagliaro CA and Utkus SP. Assessing the value of advice. Vanguard. 2019 Sept.
2. Kinniry Jr. FM et al. Putting a value on your value: Quantifying Vanguard Advisor’s Alpha. Vanguard. 2022 July.
3. Horan S. What Are the Benefits of Working with a Financial Advisor? – 2021 Study. Smart Asset. 2023 July 27.
4. Kagan J. Certified Financial PlannerTM(CFP): What It Is and How to Become One. Investopedia. 2023 Aug 3.
5. CFP Board. Our Commitment to Ethical Standards. CFP Board. 2024.
6. Staff of the Investment Adviser Regulation Office Division of Investment Management, U.S. Securities and Exchange Commission. Regulation of Investment Advisers by the U.S. Securities and Exchange Commission. 2013 Mar.
7. Hicks C. Investment Advisor vs. Financial Advisor: There is a Difference. US News & World Report. 2019 June 13.
8. Roberts K. Financial advisor vs. financial planner: What is the difference? Bankrate. 2023 Nov 21.
9. Clancy D. Average Fees for Financial Advisors in 2023. Harness Wealth. 2023 May 25.
10. Palmer B. Fee- vs. Commission-Based Advisor: What’s the Difference? Investopedia. 2023 June 20.
Achieving Promotion for Junior Faculty in Academic Medicine: An Interview With Experts
Academic medicine plays a crucial role at the crossroads of medical practice, education, and research, influencing the future landscape of healthcare. Many physicians aspire to pursue and sustain a career in academic medicine to contribute to the advancement of medical knowledge, enhance patient care, and influence the trajectory of the medical field. Opting for a career in academic medicine can offer benefits such as increased autonomy and scheduling flexibility, which can significantly improve the quality of life. In addition, engagement in scholarly activities and working in a dynamic environment with continuous learning opportunities can help mitigate burnout.
However, embarking on an academic career can be daunting for junior faculty members who face the challenge of providing clinical care while excelling in research and dedicating time to mentorship and teaching trainees. According to a report by the Association of American Medical Colleges, 38% of physicians leave academic medicine within a decade of obtaining a faculty position. Barriers to promotion and retention within academic medicine include ineffective mentorship, unclear or inconsistent promotion criteria, and disparities in gender/ethnic representation.
In this article, we interview two accomplished physicians in academic medicine who have attained the rank of professors.
Interview with Sophie Balzora, MD
Dr. Balzora is a professor of medicine at NYU Grossman School of Medicine and a practicing gastroenterologist specializing in the care of patients with inflammatory bowel disease at NYU Langone Health. She serves as the American College of Gastroenterology’s Diversity, Equity, and Inclusion Committee Chair, on the Advisory Board of ACG’s Leadership, Ethics, and Equity (LE&E) Center, and is president and cofounder of the Association of Black Gastroenterologists and Hepatologists (ABGH). Dr. Balzora was promoted to full professor 11 years after graduating from fellowship.
What would you identify as some of the most important factors that led to your success in achieving a promotion to professor of medicine?
Surround yourself with individuals whose professional and personal priorities align with yours. To achieve this, it is essential to gain an understanding of what is important to you, what you envision your success to look like, and establish a timeline to achieve it. The concept of personal success and how to best achieve it will absolutely change as you grow, and that is okay and expected. Connecting with those outside of your clinical interests, at other institutions, and even outside of the medical field, can help you achieve these goals and better shape how you see your career unfolding and how you want it to look.
Historically, the proportion of physicians who achieve professorship is lower among women compared with men. What do you believe are some of the barriers involved in this, and how would you counsel women who are interested in pursuing the rank of professor?
Systemic gender bias and discrimination, over-mentorship and under-sponsorship, inconsistent parental leave, and delayed parenthood are a few of the factors that contribute to the observed disparities in academic rank. Predictably, for women from underrepresented backgrounds in medicine, the chasm grows.
What has helped me most is to keep my eyes on the prize, and to recognize that the prize is different for everyone. It’s important not to make direct comparisons to any other individual, because they are not you. Harness what makes you different and drown out the naysayers — the “we’ve never seen this done before” camp, the “it’s too soon [for someone like you] to go up for promotion” folks. While these voices are sometimes well intentioned, they can distract you from your goals and ambitions because they are rooted in bias and adherence to traditional expectations. To do something new, and to change the game, requires going against the grain and utilizing your skills and talents to achieve what you want to achieve in a way that works for you.
What are some practical tips you have for junior gastroenterologists to track their promotion in academia?
- Keep your curriculum vitae (CV) up to date and formatted to your institutional guidelines. Ensure that you document your academic activities, even if it doesn’t seem important in the moment. When it’s time to submit that promotion portfolio, you want to be ready and organized.
- Remember: “No” is a full sentence, and saying it takes practice and time and confidence. It is a skill I still struggle to adopt at times, but it’s important to recognize the power of no, for it opens opportunities to say yes to other things.
- Lift as you climb — a critical part of changing the status quo is fostering the future of those underrepresented in medicine. A professional goal of mine that keeps me steady and passionate is to create supporting and enriching systemic and institutional changes that work to dismantle the obstacles perpetuating disparities in academic rank for women and those underrepresented in medicine. Discovering your “why” is a complex, difficult, and rewarding journey.
Interview with Mark Schattner, MD, AGAF
Dr. Schattner is a professor of clinical medicine at Weill Cornell College of Medicine and chief of the gastroenterology, hepatology, and nutrition service at Memorial Sloan Kettering Cancer Center, both in New York. He is a former president of the New York Society for Gastrointestinal Endoscopy and a fellow of the AGA and ASGE.
In your role as chief, you serve as a mentor for early career gastroenterologists for pursuing career promotion. What advice do you have for achieving this?
Promoting junior faculty is one of the prime responsibilities of a service chief. Generally, the early steps of promotion are straightforward, with criteria becoming more stringent as you progress. I think it is critical to understand the criteria used by promotion committees and to be aware of the various available tracks. I believe every meeting a junior faculty member has with their service chief should include, at the least, a brief check-in on where they are in the promotion process and plans (both short term and long term) to move forward. Successful promotion is facilitated when done upon a solid foundation of production and accomplishment. It is very challenging or even impossible when trying to piece together a package from discordant activities.
Most institutions require or encourage academic involvement at both national and international levels for career promotion. Do you have advice for junior faculty about how to achieve this type of recognition or experience?
The easiest place to start is with regional professional societies. Active involvement in these local societies fosters valuable networking and lays the groundwork for involvement at the national or international level. I would strongly encourage junior faculty to seek opportunities for a leadership position at any level in these societies and move up the ladder as their career matures. This is also a very good avenue to network and get invited to join collaborative research projects, which can be a fruitful means to enhance your academic productivity.
In your opinion, what factors are likely to hinder or delay an individual’s promotion?
I think it is crucial to consider the career track you are on. If you are very clinically productive and love to teach, that is completely appropriate, and most institutions will recognize the value of that and promote you along a clinical-educator tract. On the other hand, if you have a passion for research and can successfully lead research and compete for grants, then you would move along a traditional tenure track. It is also critical to think ahead, know the criteria on which you will be judged, and incorporate that into your practice early. Trying to scramble to enhance your CV in a short time just for promotion will likely prove ineffective.
Do you have advice for junior faculty who have families about how to manage career goals but also prioritize time with family?
There is no one-size-fits-all approach to this. I think this requires a lot of shared decision-making with your family. Compromise will undoubtedly be required. For example, I always chose to live in close proximity to my workplace, eliminating any commuting time. This choice really allowed me spend time with my family.
In conclusion, a career in academic medicine presents both opportunities and challenges. A successful academic career, and achieving promotion to the rank of professor of medicine, requires a combination of factors including understanding institution-specific criteria for promotion, proactive engagement at the regional and national level, and envisioning your career goals and creating a timeline to achieve them. There are challenges to promotion, including navigating systemic biases and balancing career goals with family commitments, which also requires consideration and open communication. Ultimately, we hope these insights provide valuable guidance and advice for junior faculty who are navigating this complex environment of academic medicine and are motivated toward achieving professional fulfillment and satisfaction in their careers.
Dr. Rolston is based in the Department of Gastroenterology, Hepatology, and Nutrition, Memorial Sloan Kettering Cancer Center, New York. She reports no conflicts in relation this article. Dr. Balzora and Dr. Schattner are based in the Division of Gastroenterology and Hepatology, New York University Langone Health, New York. Dr. Schattner is a consultant for Boston Scientific and Novo Nordisk. Dr. Balzora reports no conflicts in relation to this article.
References
Campbell KM. Mitigating the isolation of minoritized faculty in academic medicine. J Gen Intern Med. 2023 May. doi: 10.1007/s11606-022-07982-8.
Howard-Anderson JR et al. Strategies for developing a successful career in academic medicine. Am J Med Sci. 2024 Apr. doi: 10.1016/j.amjms.2023.12.010.
Murphy M et al. Women’s experiences of promotion and tenure in academic medicine and potential implications for gender disparities in career advancement: A qualitative analysis. JAMA Netw Open. 2021 Sep 1. doi: 10.1001/jamanetworkopen.2021.25843.
Sambunjak D et al. Mentoring in academic medicine: A systematic review. JAMA. 2006 Sep 6. doi: 10.1001/jama.296.9.1103.
Shen MR et al. Impact of mentoring on academic career success for women in medicine: A systematic review. Acad Med. 2022 Mar 1. doi: 10.1097/ACM.0000000000004563.
Academic medicine plays a crucial role at the crossroads of medical practice, education, and research, influencing the future landscape of healthcare. Many physicians aspire to pursue and sustain a career in academic medicine to contribute to the advancement of medical knowledge, enhance patient care, and influence the trajectory of the medical field. Opting for a career in academic medicine can offer benefits such as increased autonomy and scheduling flexibility, which can significantly improve the quality of life. In addition, engagement in scholarly activities and working in a dynamic environment with continuous learning opportunities can help mitigate burnout.
However, embarking on an academic career can be daunting for junior faculty members who face the challenge of providing clinical care while excelling in research and dedicating time to mentorship and teaching trainees. According to a report by the Association of American Medical Colleges, 38% of physicians leave academic medicine within a decade of obtaining a faculty position. Barriers to promotion and retention within academic medicine include ineffective mentorship, unclear or inconsistent promotion criteria, and disparities in gender/ethnic representation.
In this article, we interview two accomplished physicians in academic medicine who have attained the rank of professors.
Interview with Sophie Balzora, MD
Dr. Balzora is a professor of medicine at NYU Grossman School of Medicine and a practicing gastroenterologist specializing in the care of patients with inflammatory bowel disease at NYU Langone Health. She serves as the American College of Gastroenterology’s Diversity, Equity, and Inclusion Committee Chair, on the Advisory Board of ACG’s Leadership, Ethics, and Equity (LE&E) Center, and is president and cofounder of the Association of Black Gastroenterologists and Hepatologists (ABGH). Dr. Balzora was promoted to full professor 11 years after graduating from fellowship.
What would you identify as some of the most important factors that led to your success in achieving a promotion to professor of medicine?
Surround yourself with individuals whose professional and personal priorities align with yours. To achieve this, it is essential to gain an understanding of what is important to you, what you envision your success to look like, and establish a timeline to achieve it. The concept of personal success and how to best achieve it will absolutely change as you grow, and that is okay and expected. Connecting with those outside of your clinical interests, at other institutions, and even outside of the medical field, can help you achieve these goals and better shape how you see your career unfolding and how you want it to look.
Historically, the proportion of physicians who achieve professorship is lower among women compared with men. What do you believe are some of the barriers involved in this, and how would you counsel women who are interested in pursuing the rank of professor?
Systemic gender bias and discrimination, over-mentorship and under-sponsorship, inconsistent parental leave, and delayed parenthood are a few of the factors that contribute to the observed disparities in academic rank. Predictably, for women from underrepresented backgrounds in medicine, the chasm grows.
What has helped me most is to keep my eyes on the prize, and to recognize that the prize is different for everyone. It’s important not to make direct comparisons to any other individual, because they are not you. Harness what makes you different and drown out the naysayers — the “we’ve never seen this done before” camp, the “it’s too soon [for someone like you] to go up for promotion” folks. While these voices are sometimes well intentioned, they can distract you from your goals and ambitions because they are rooted in bias and adherence to traditional expectations. To do something new, and to change the game, requires going against the grain and utilizing your skills and talents to achieve what you want to achieve in a way that works for you.
What are some practical tips you have for junior gastroenterologists to track their promotion in academia?
- Keep your curriculum vitae (CV) up to date and formatted to your institutional guidelines. Ensure that you document your academic activities, even if it doesn’t seem important in the moment. When it’s time to submit that promotion portfolio, you want to be ready and organized.
- Remember: “No” is a full sentence, and saying it takes practice and time and confidence. It is a skill I still struggle to adopt at times, but it’s important to recognize the power of no, for it opens opportunities to say yes to other things.
- Lift as you climb — a critical part of changing the status quo is fostering the future of those underrepresented in medicine. A professional goal of mine that keeps me steady and passionate is to create supporting and enriching systemic and institutional changes that work to dismantle the obstacles perpetuating disparities in academic rank for women and those underrepresented in medicine. Discovering your “why” is a complex, difficult, and rewarding journey.
Interview with Mark Schattner, MD, AGAF
Dr. Schattner is a professor of clinical medicine at Weill Cornell College of Medicine and chief of the gastroenterology, hepatology, and nutrition service at Memorial Sloan Kettering Cancer Center, both in New York. He is a former president of the New York Society for Gastrointestinal Endoscopy and a fellow of the AGA and ASGE.
In your role as chief, you serve as a mentor for early career gastroenterologists for pursuing career promotion. What advice do you have for achieving this?
Promoting junior faculty is one of the prime responsibilities of a service chief. Generally, the early steps of promotion are straightforward, with criteria becoming more stringent as you progress. I think it is critical to understand the criteria used by promotion committees and to be aware of the various available tracks. I believe every meeting a junior faculty member has with their service chief should include, at the least, a brief check-in on where they are in the promotion process and plans (both short term and long term) to move forward. Successful promotion is facilitated when done upon a solid foundation of production and accomplishment. It is very challenging or even impossible when trying to piece together a package from discordant activities.
Most institutions require or encourage academic involvement at both national and international levels for career promotion. Do you have advice for junior faculty about how to achieve this type of recognition or experience?
The easiest place to start is with regional professional societies. Active involvement in these local societies fosters valuable networking and lays the groundwork for involvement at the national or international level. I would strongly encourage junior faculty to seek opportunities for a leadership position at any level in these societies and move up the ladder as their career matures. This is also a very good avenue to network and get invited to join collaborative research projects, which can be a fruitful means to enhance your academic productivity.
In your opinion, what factors are likely to hinder or delay an individual’s promotion?
I think it is crucial to consider the career track you are on. If you are very clinically productive and love to teach, that is completely appropriate, and most institutions will recognize the value of that and promote you along a clinical-educator tract. On the other hand, if you have a passion for research and can successfully lead research and compete for grants, then you would move along a traditional tenure track. It is also critical to think ahead, know the criteria on which you will be judged, and incorporate that into your practice early. Trying to scramble to enhance your CV in a short time just for promotion will likely prove ineffective.
Do you have advice for junior faculty who have families about how to manage career goals but also prioritize time with family?
There is no one-size-fits-all approach to this. I think this requires a lot of shared decision-making with your family. Compromise will undoubtedly be required. For example, I always chose to live in close proximity to my workplace, eliminating any commuting time. This choice really allowed me spend time with my family.
In conclusion, a career in academic medicine presents both opportunities and challenges. A successful academic career, and achieving promotion to the rank of professor of medicine, requires a combination of factors including understanding institution-specific criteria for promotion, proactive engagement at the regional and national level, and envisioning your career goals and creating a timeline to achieve them. There are challenges to promotion, including navigating systemic biases and balancing career goals with family commitments, which also requires consideration and open communication. Ultimately, we hope these insights provide valuable guidance and advice for junior faculty who are navigating this complex environment of academic medicine and are motivated toward achieving professional fulfillment and satisfaction in their careers.
Dr. Rolston is based in the Department of Gastroenterology, Hepatology, and Nutrition, Memorial Sloan Kettering Cancer Center, New York. She reports no conflicts in relation this article. Dr. Balzora and Dr. Schattner are based in the Division of Gastroenterology and Hepatology, New York University Langone Health, New York. Dr. Schattner is a consultant for Boston Scientific and Novo Nordisk. Dr. Balzora reports no conflicts in relation to this article.
References
Campbell KM. Mitigating the isolation of minoritized faculty in academic medicine. J Gen Intern Med. 2023 May. doi: 10.1007/s11606-022-07982-8.
Howard-Anderson JR et al. Strategies for developing a successful career in academic medicine. Am J Med Sci. 2024 Apr. doi: 10.1016/j.amjms.2023.12.010.
Murphy M et al. Women’s experiences of promotion and tenure in academic medicine and potential implications for gender disparities in career advancement: A qualitative analysis. JAMA Netw Open. 2021 Sep 1. doi: 10.1001/jamanetworkopen.2021.25843.
Sambunjak D et al. Mentoring in academic medicine: A systematic review. JAMA. 2006 Sep 6. doi: 10.1001/jama.296.9.1103.
Shen MR et al. Impact of mentoring on academic career success for women in medicine: A systematic review. Acad Med. 2022 Mar 1. doi: 10.1097/ACM.0000000000004563.
Academic medicine plays a crucial role at the crossroads of medical practice, education, and research, influencing the future landscape of healthcare. Many physicians aspire to pursue and sustain a career in academic medicine to contribute to the advancement of medical knowledge, enhance patient care, and influence the trajectory of the medical field. Opting for a career in academic medicine can offer benefits such as increased autonomy and scheduling flexibility, which can significantly improve the quality of life. In addition, engagement in scholarly activities and working in a dynamic environment with continuous learning opportunities can help mitigate burnout.
However, embarking on an academic career can be daunting for junior faculty members who face the challenge of providing clinical care while excelling in research and dedicating time to mentorship and teaching trainees. According to a report by the Association of American Medical Colleges, 38% of physicians leave academic medicine within a decade of obtaining a faculty position. Barriers to promotion and retention within academic medicine include ineffective mentorship, unclear or inconsistent promotion criteria, and disparities in gender/ethnic representation.
In this article, we interview two accomplished physicians in academic medicine who have attained the rank of professors.
Interview with Sophie Balzora, MD
Dr. Balzora is a professor of medicine at NYU Grossman School of Medicine and a practicing gastroenterologist specializing in the care of patients with inflammatory bowel disease at NYU Langone Health. She serves as the American College of Gastroenterology’s Diversity, Equity, and Inclusion Committee Chair, on the Advisory Board of ACG’s Leadership, Ethics, and Equity (LE&E) Center, and is president and cofounder of the Association of Black Gastroenterologists and Hepatologists (ABGH). Dr. Balzora was promoted to full professor 11 years after graduating from fellowship.
What would you identify as some of the most important factors that led to your success in achieving a promotion to professor of medicine?
Surround yourself with individuals whose professional and personal priorities align with yours. To achieve this, it is essential to gain an understanding of what is important to you, what you envision your success to look like, and establish a timeline to achieve it. The concept of personal success and how to best achieve it will absolutely change as you grow, and that is okay and expected. Connecting with those outside of your clinical interests, at other institutions, and even outside of the medical field, can help you achieve these goals and better shape how you see your career unfolding and how you want it to look.
Historically, the proportion of physicians who achieve professorship is lower among women compared with men. What do you believe are some of the barriers involved in this, and how would you counsel women who are interested in pursuing the rank of professor?
Systemic gender bias and discrimination, over-mentorship and under-sponsorship, inconsistent parental leave, and delayed parenthood are a few of the factors that contribute to the observed disparities in academic rank. Predictably, for women from underrepresented backgrounds in medicine, the chasm grows.
What has helped me most is to keep my eyes on the prize, and to recognize that the prize is different for everyone. It’s important not to make direct comparisons to any other individual, because they are not you. Harness what makes you different and drown out the naysayers — the “we’ve never seen this done before” camp, the “it’s too soon [for someone like you] to go up for promotion” folks. While these voices are sometimes well intentioned, they can distract you from your goals and ambitions because they are rooted in bias and adherence to traditional expectations. To do something new, and to change the game, requires going against the grain and utilizing your skills and talents to achieve what you want to achieve in a way that works for you.
What are some practical tips you have for junior gastroenterologists to track their promotion in academia?
- Keep your curriculum vitae (CV) up to date and formatted to your institutional guidelines. Ensure that you document your academic activities, even if it doesn’t seem important in the moment. When it’s time to submit that promotion portfolio, you want to be ready and organized.
- Remember: “No” is a full sentence, and saying it takes practice and time and confidence. It is a skill I still struggle to adopt at times, but it’s important to recognize the power of no, for it opens opportunities to say yes to other things.
- Lift as you climb — a critical part of changing the status quo is fostering the future of those underrepresented in medicine. A professional goal of mine that keeps me steady and passionate is to create supporting and enriching systemic and institutional changes that work to dismantle the obstacles perpetuating disparities in academic rank for women and those underrepresented in medicine. Discovering your “why” is a complex, difficult, and rewarding journey.
Interview with Mark Schattner, MD, AGAF
Dr. Schattner is a professor of clinical medicine at Weill Cornell College of Medicine and chief of the gastroenterology, hepatology, and nutrition service at Memorial Sloan Kettering Cancer Center, both in New York. He is a former president of the New York Society for Gastrointestinal Endoscopy and a fellow of the AGA and ASGE.
In your role as chief, you serve as a mentor for early career gastroenterologists for pursuing career promotion. What advice do you have for achieving this?
Promoting junior faculty is one of the prime responsibilities of a service chief. Generally, the early steps of promotion are straightforward, with criteria becoming more stringent as you progress. I think it is critical to understand the criteria used by promotion committees and to be aware of the various available tracks. I believe every meeting a junior faculty member has with their service chief should include, at the least, a brief check-in on where they are in the promotion process and plans (both short term and long term) to move forward. Successful promotion is facilitated when done upon a solid foundation of production and accomplishment. It is very challenging or even impossible when trying to piece together a package from discordant activities.
Most institutions require or encourage academic involvement at both national and international levels for career promotion. Do you have advice for junior faculty about how to achieve this type of recognition or experience?
The easiest place to start is with regional professional societies. Active involvement in these local societies fosters valuable networking and lays the groundwork for involvement at the national or international level. I would strongly encourage junior faculty to seek opportunities for a leadership position at any level in these societies and move up the ladder as their career matures. This is also a very good avenue to network and get invited to join collaborative research projects, which can be a fruitful means to enhance your academic productivity.
In your opinion, what factors are likely to hinder or delay an individual’s promotion?
I think it is crucial to consider the career track you are on. If you are very clinically productive and love to teach, that is completely appropriate, and most institutions will recognize the value of that and promote you along a clinical-educator tract. On the other hand, if you have a passion for research and can successfully lead research and compete for grants, then you would move along a traditional tenure track. It is also critical to think ahead, know the criteria on which you will be judged, and incorporate that into your practice early. Trying to scramble to enhance your CV in a short time just for promotion will likely prove ineffective.
Do you have advice for junior faculty who have families about how to manage career goals but also prioritize time with family?
There is no one-size-fits-all approach to this. I think this requires a lot of shared decision-making with your family. Compromise will undoubtedly be required. For example, I always chose to live in close proximity to my workplace, eliminating any commuting time. This choice really allowed me spend time with my family.
In conclusion, a career in academic medicine presents both opportunities and challenges. A successful academic career, and achieving promotion to the rank of professor of medicine, requires a combination of factors including understanding institution-specific criteria for promotion, proactive engagement at the regional and national level, and envisioning your career goals and creating a timeline to achieve them. There are challenges to promotion, including navigating systemic biases and balancing career goals with family commitments, which also requires consideration and open communication. Ultimately, we hope these insights provide valuable guidance and advice for junior faculty who are navigating this complex environment of academic medicine and are motivated toward achieving professional fulfillment and satisfaction in their careers.
Dr. Rolston is based in the Department of Gastroenterology, Hepatology, and Nutrition, Memorial Sloan Kettering Cancer Center, New York. She reports no conflicts in relation this article. Dr. Balzora and Dr. Schattner are based in the Division of Gastroenterology and Hepatology, New York University Langone Health, New York. Dr. Schattner is a consultant for Boston Scientific and Novo Nordisk. Dr. Balzora reports no conflicts in relation to this article.
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