We are proud to announce the 2024 recipients of our annual recognition prizes, given in honor of outstanding contributions and achievements in gastroenterology and hepatology.

Congratulations to Bishr Omary, MD, PhD, for receiving AGA’s highest honor, the Julius Friedenwald Medal.

Dr. Omary

Presented annually since 1941, this award recognizes a physician for lifelong contributions to the field of gastroenterology.

AGA

2024 recognition prize recipients:

• Julius Friedenwald Medal: Bishr Omary, MD, PhD
• William Beaumont Prize: Hashem B. El-Serag, MD, MPH
• Distinguished Achievement Award in Basic Science: Jerrold R. Turner, MD, PhD, AGAF
• Distinguished Service Award in Diversity, Equity, and Inclusion: Sophie Balzora, MD
• Distinguished Clinician Award in Private Practice: Scott Ketover, MD, AGAF, FASGE
• Distinguished Clinician Award in Academic Practice: Shiv Kumar Sarin, MD
• Distinguished Educator Award: David Katzka, MD, AGAF
• Distinguished Mentor Award: John Pandolfino, MD
• Young Investigator Award in Clinical Science: Mingyang Song, ScD

We are proud to announce the 2024 recipients of our annual recognition prizes, given in honor of outstanding contributions and achievements in gastroenterology and hepatology.

Congratulations to Bishr Omary, MD, PhD, for receiving AGA’s highest honor, the Julius Friedenwald Medal.

Dr. Omary

Presented annually since 1941, this award recognizes a physician for lifelong contributions to the field of gastroenterology.

AGA

2024 recognition prize recipients:

• Julius Friedenwald Medal: Bishr Omary, MD, PhD
• William Beaumont Prize: Hashem B. El-Serag, MD, MPH
• Distinguished Achievement Award in Basic Science: Jerrold R. Turner, MD, PhD, AGAF
• Distinguished Service Award in Diversity, Equity, and Inclusion: Sophie Balzora, MD
• Distinguished Clinician Award in Private Practice: Scott Ketover, MD, AGAF, FASGE
• Distinguished Clinician Award in Academic Practice: Shiv Kumar Sarin, MD
• Distinguished Educator Award: David Katzka, MD, AGAF
• Distinguished Mentor Award: John Pandolfino, MD
• Young Investigator Award in Clinical Science: Mingyang Song, ScD

We are proud to announce the 2024 recipients of our annual recognition prizes, given in honor of outstanding contributions and achievements in gastroenterology and hepatology.

Congratulations to Bishr Omary, MD, PhD, for receiving AGA’s highest honor, the Julius Friedenwald Medal.

Dr. Omary

Presented annually since 1941, this award recognizes a physician for lifelong contributions to the field of gastroenterology.

AGA

2024 recognition prize recipients:

• Julius Friedenwald Medal: Bishr Omary, MD, PhD
• William Beaumont Prize: Hashem B. El-Serag, MD, MPH
• Distinguished Achievement Award in Basic Science: Jerrold R. Turner, MD, PhD, AGAF
• Distinguished Service Award in Diversity, Equity, and Inclusion: Sophie Balzora, MD
• Distinguished Clinician Award in Private Practice: Scott Ketover, MD, AGAF, FASGE
• Distinguished Clinician Award in Academic Practice: Shiv Kumar Sarin, MD
• Distinguished Educator Award: David Katzka, MD, AGAF
• Distinguished Mentor Award: John Pandolfino, MD
• Young Investigator Award in Clinical Science: Mingyang Song, ScD

CHICAGO — At the 2024 AGA Tech Summit, held April 11-12 at the Chicago headquarters of MATTER, a global healthcare startup incubator, five companies made their pitch to be the winner of the Shark Tank competition that recognizes an outstanding tech start up in the gastroenterology field.

After the companies’ rapid-fire pitches and Q&A sessions, four judges convened to determine a winner and returned to make an announcement.

The winner was Arithmedics, which uses AI technology to automate billing codes. Founder Venthan Elango, PhD, has worked as a software engineer at Google, Urban Engines, and Georgia Tech, and his wife of 17 years is Renumathy Dhanasekaran, MD, PhD, a gastroenterologist and assistant professor of medicine at Stanford (California) University.

Their marriage has brought a unique perspective, according to Dr. Elango. “There isn’t a single day that goes by when she talks to me about the inefficiencies in healthcare, and then I say, ‘this can be easily solved with a software solution,’ ” he said.

Arithmedics

Stanford University

• Aspero Medical: Balloon overtube that maximizes frictional properties to improve mucosal wall traction and anchoring consistency. (Voted ‘fan favorite’ by AGA Tech Summit attendees)
• Aurora Medical Technologies: Minimally invasive, guided, tissue-anchoring suturing system for complex endoscopic procedures.
• Ergami Endoscopy: Flexible overtube capable of automatic insertion and fixation in the colon, which could potentially eliminate sedation and prevent endoscopic injuries to the physician.
• Lazurite: Wireless surgical camera that eliminates the need for light or video cables, avoiding the associated fire, trip, and contamination hazards.

The judges were swayed by Arithmedics’ practical solution to a widespread problem. “There is for sure a need in terms of inaccurate billing and billing codes that are wrong. There’s lost revenue for physicians around that. So I think we were really focused from a judging standpoint on the fact that their solution was filling truly an unmet need,” said judge Andrea Vossler, a managing director of Varia Ventures, which has partnered with AGA to launch and manage the GI Opportunity Fund, an AGA-member venture fund.

“We were really focused on how to assist physicians in terms of supporting their practices, and really changing what you’re doing. I think AI has the ability to do that, so we liked that about the company,” she added.

The company is an example of how AI is poised to alter healthcare, according to Ms. Vossler. “I think it’s massive. I think we’re at the very beginning of its impact on healthcare,” she said.

Another judge had a similar view. “They won because there is a screaming need to fix billing. So, it’s well known that lots of money is indeed lost in billing practices, which are stressful for office personnel and stressful for physicians. They can fulfill a long-standing need, and we thought that that was the success story,” said Christopher Gostout, MD, emeritus professor of medicine at Mayo Clinic in Rochester, Minnesota.

Dr. Gostout offered advice for gastroenterologists and other physicians interested in starting tech companies. It’s imperative to be a realist, he said. “Is there a real market for it, or [is it just] a niche market? Does your device have legs — can it expand and can evolve into other [spin-off] products? These are things you need to think about because one-offs or single-trick ponies are pretty hard to move along now,” said Dr. Gostout.

He recommended that entrepreneurs apply for Small Business Innovation Research (SBIR) grants. “I think it’s a great opportunity to bring in money and get the ball rolling.”

Finally, he advised entrepreneurs to be thoughtful about their advisory groups. Founders may be tempted to find the highest profile names they can to give the business gravitas, but those big names may not have the best knowledge base to understand the problems that the technology is meant to address. “I’ve seen businesses fail because they went for marquee names that really were not helpful, and they didn’t do their due diligence in seeking out really useful value. You don’t need a lot of advisers, just a couple of really good ones,” said Dr. Gostout.

The summit was sponsored by the AGA Center for GI Innovation and Technology.

Dr. Gostout has founded and advises AdaptivEndo and Lean Medical. He is a consultant to Boston Scientific. Dr. Dhanasekaran has no financial disclosures. Ms. Vossler is an employee of Varia Ventures, which is an investment partner to AGA. Dr. Elango is an employee of Arithmedics.

CHICAGO — At the 2024 AGA Tech Summit, held April 11-12 at the Chicago headquarters of MATTER, a global healthcare startup incubator, five companies made their pitch to be the winner of the Shark Tank competition that recognizes an outstanding tech start up in the gastroenterology field.

After the companies’ rapid-fire pitches and Q&A sessions, four judges convened to determine a winner and returned to make an announcement.

The winner was Arithmedics, which uses AI technology to automate billing codes. Founder Venthan Elango, PhD, has worked as a software engineer at Google, Urban Engines, and Georgia Tech, and his wife of 17 years is Renumathy Dhanasekaran, MD, PhD, a gastroenterologist and assistant professor of medicine at Stanford (California) University.

Their marriage has brought a unique perspective, according to Dr. Elango. “There isn’t a single day that goes by when she talks to me about the inefficiencies in healthcare, and then I say, ‘this can be easily solved with a software solution,’ ” he said.

Arithmedics

Stanford University

• Aspero Medical: Balloon overtube that maximizes frictional properties to improve mucosal wall traction and anchoring consistency. (Voted ‘fan favorite’ by AGA Tech Summit attendees)
• Aurora Medical Technologies: Minimally invasive, guided, tissue-anchoring suturing system for complex endoscopic procedures.
• Ergami Endoscopy: Flexible overtube capable of automatic insertion and fixation in the colon, which could potentially eliminate sedation and prevent endoscopic injuries to the physician.
• Lazurite: Wireless surgical camera that eliminates the need for light or video cables, avoiding the associated fire, trip, and contamination hazards.

The judges were swayed by Arithmedics’ practical solution to a widespread problem. “There is for sure a need in terms of inaccurate billing and billing codes that are wrong. There’s lost revenue for physicians around that. So I think we were really focused from a judging standpoint on the fact that their solution was filling truly an unmet need,” said judge Andrea Vossler, a managing director of Varia Ventures, which has partnered with AGA to launch and manage the GI Opportunity Fund, an AGA-member venture fund.

“We were really focused on how to assist physicians in terms of supporting their practices, and really changing what you’re doing. I think AI has the ability to do that, so we liked that about the company,” she added.

The company is an example of how AI is poised to alter healthcare, according to Ms. Vossler. “I think it’s massive. I think we’re at the very beginning of its impact on healthcare,” she said.

Another judge had a similar view. “They won because there is a screaming need to fix billing. So, it’s well known that lots of money is indeed lost in billing practices, which are stressful for office personnel and stressful for physicians. They can fulfill a long-standing need, and we thought that that was the success story,” said Christopher Gostout, MD, emeritus professor of medicine at Mayo Clinic in Rochester, Minnesota.

Dr. Gostout offered advice for gastroenterologists and other physicians interested in starting tech companies. It’s imperative to be a realist, he said. “Is there a real market for it, or [is it just] a niche market? Does your device have legs — can it expand and can evolve into other [spin-off] products? These are things you need to think about because one-offs or single-trick ponies are pretty hard to move along now,” said Dr. Gostout.

He recommended that entrepreneurs apply for Small Business Innovation Research (SBIR) grants. “I think it’s a great opportunity to bring in money and get the ball rolling.”

Finally, he advised entrepreneurs to be thoughtful about their advisory groups. Founders may be tempted to find the highest profile names they can to give the business gravitas, but those big names may not have the best knowledge base to understand the problems that the technology is meant to address. “I’ve seen businesses fail because they went for marquee names that really were not helpful, and they didn’t do their due diligence in seeking out really useful value. You don’t need a lot of advisers, just a couple of really good ones,” said Dr. Gostout.

The summit was sponsored by the AGA Center for GI Innovation and Technology.

Dr. Gostout has founded and advises AdaptivEndo and Lean Medical. He is a consultant to Boston Scientific. Dr. Dhanasekaran has no financial disclosures. Ms. Vossler is an employee of Varia Ventures, which is an investment partner to AGA. Dr. Elango is an employee of Arithmedics.

CHICAGO — At the 2024 AGA Tech Summit, held April 11-12 at the Chicago headquarters of MATTER, a global healthcare startup incubator, five companies made their pitch to be the winner of the Shark Tank competition that recognizes an outstanding tech start up in the gastroenterology field.

After the companies’ rapid-fire pitches and Q&A sessions, four judges convened to determine a winner and returned to make an announcement.

The winner was Arithmedics, which uses AI technology to automate billing codes. Founder Venthan Elango, PhD, has worked as a software engineer at Google, Urban Engines, and Georgia Tech, and his wife of 17 years is Renumathy Dhanasekaran, MD, PhD, a gastroenterologist and assistant professor of medicine at Stanford (California) University.

Their marriage has brought a unique perspective, according to Dr. Elango. “There isn’t a single day that goes by when she talks to me about the inefficiencies in healthcare, and then I say, ‘this can be easily solved with a software solution,’ ” he said.

Arithmedics

Stanford University

• Aspero Medical: Balloon overtube that maximizes frictional properties to improve mucosal wall traction and anchoring consistency. (Voted ‘fan favorite’ by AGA Tech Summit attendees)
• Aurora Medical Technologies: Minimally invasive, guided, tissue-anchoring suturing system for complex endoscopic procedures.
• Ergami Endoscopy: Flexible overtube capable of automatic insertion and fixation in the colon, which could potentially eliminate sedation and prevent endoscopic injuries to the physician.
• Lazurite: Wireless surgical camera that eliminates the need for light or video cables, avoiding the associated fire, trip, and contamination hazards.

The judges were swayed by Arithmedics’ practical solution to a widespread problem. “There is for sure a need in terms of inaccurate billing and billing codes that are wrong. There’s lost revenue for physicians around that. So I think we were really focused from a judging standpoint on the fact that their solution was filling truly an unmet need,” said judge Andrea Vossler, a managing director of Varia Ventures, which has partnered with AGA to launch and manage the GI Opportunity Fund, an AGA-member venture fund.

“We were really focused on how to assist physicians in terms of supporting their practices, and really changing what you’re doing. I think AI has the ability to do that, so we liked that about the company,” she added.

The company is an example of how AI is poised to alter healthcare, according to Ms. Vossler. “I think it’s massive. I think we’re at the very beginning of its impact on healthcare,” she said.

Another judge had a similar view. “They won because there is a screaming need to fix billing. So, it’s well known that lots of money is indeed lost in billing practices, which are stressful for office personnel and stressful for physicians. They can fulfill a long-standing need, and we thought that that was the success story,” said Christopher Gostout, MD, emeritus professor of medicine at Mayo Clinic in Rochester, Minnesota.

Dr. Gostout offered advice for gastroenterologists and other physicians interested in starting tech companies. It’s imperative to be a realist, he said. “Is there a real market for it, or [is it just] a niche market? Does your device have legs — can it expand and can evolve into other [spin-off] products? These are things you need to think about because one-offs or single-trick ponies are pretty hard to move along now,” said Dr. Gostout.

He recommended that entrepreneurs apply for Small Business Innovation Research (SBIR) grants. “I think it’s a great opportunity to bring in money and get the ball rolling.”

Finally, he advised entrepreneurs to be thoughtful about their advisory groups. Founders may be tempted to find the highest profile names they can to give the business gravitas, but those big names may not have the best knowledge base to understand the problems that the technology is meant to address. “I’ve seen businesses fail because they went for marquee names that really were not helpful, and they didn’t do their due diligence in seeking out really useful value. You don’t need a lot of advisers, just a couple of really good ones,” said Dr. Gostout.

The summit was sponsored by the AGA Center for GI Innovation and Technology.

Dr. Gostout has founded and advises AdaptivEndo and Lean Medical. He is a consultant to Boston Scientific. Dr. Dhanasekaran has no financial disclosures. Ms. Vossler is an employee of Varia Ventures, which is an investment partner to AGA. Dr. Elango is an employee of Arithmedics.

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.

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].

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.

There is no association between the SARS-CoV-2 vaccine and the risk for new-onset seizure, data from a new meta-analysis of six randomized, placebo-controlled clinical trials (RCTs) showed.

Results of the pooled analysis that included 63,500 individuals vaccinated with SARS-CoV-2 and 55,000 who received a placebo vaccine showed there was no significant difference between the two groups with respect to new-onset seizures at 28- or 43-day follow-up.

Regarding new-onset seizures in the general population, there was no statistically significant difference in risk for seizure incidence among vaccinated individuals vs placebo recipients, according to our meta-analysis, wrote the investigators, led by Ali Rafati, MD, MPH, Iran University of Medical Sciences in Tehran.

The findings were published online in JAMA Neurology.

Mixed Results

Results from previous research have been mixed regarding the link between the SARS-CoV-2 vaccination and new-onset seizures, with some showing an association.

To learn more about the possible association between the vaccines and new-onset seizures, the researchers conducted a literature review and identified six RCTs that measured adverse events following SARS-CoV-2 vaccinations (including messenger RNA, viral vector, and inactivated virus) vs placebo or other vaccines.

While five of the studies defined new-onset seizures according to the Medical Dictionary for Regulatory Activities, trial investigators in the sixth RCT assessed and determined new-onset seizures in participants.

Participants received two vaccinations 28 days apart in five RCTs and only one vaccine in the sixth trial.

The research team searched the data for new-onset seizure in the 28 days following one or both COVID vaccinations.

No Link Found

After comparing the incidence of new-onset seizure between the 63,500 vaccine (nine new-onset seizures, 0.014%) and 55,000 placebo recipients (one new-onset seizure, 0.002%), investigators found no significant difference between the two groups (odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12)

Investigators also sliced the data several ways to see if it would yield different results. When they analyzed data by vaccine platform (viral vector) and age group (children), they didn’t observe significant differences in new-onset data.

The researchers also searched for data beyond the month following the injection to encompass the entire blinded phase, so they analyzed the results of three RCTs that reported adverse events up to 162 days after the vaccine.

After pooling the results from the three studies, investigators found no statistical difference between the vaccine and placebo groups in terms of the new-onset seizure (OR, 2.31; 95% CI, 0.86%-3.23; P > .99)

Study limitations included the missing information on vaccine doses or risk factors for the development of seizures. Also, the RCTs included in the meta-analysis were conducted at different times, so the SARS-CoV-2 vaccines may have differed in their composition and efficacy.

“The global vaccination drive against SARS-CoV-2 has been a monumental effort in combating the pandemic. SARS-CoV-2 vaccinations that are now available appear safe and appropriate,” the authors wrote.

There were no study funding sources or disclosures reported.

A version of this article appeared on Medscape.com.

There is no association between the SARS-CoV-2 vaccine and the risk for new-onset seizure, data from a new meta-analysis of six randomized, placebo-controlled clinical trials (RCTs) showed.

Results of the pooled analysis that included 63,500 individuals vaccinated with SARS-CoV-2 and 55,000 who received a placebo vaccine showed there was no significant difference between the two groups with respect to new-onset seizures at 28- or 43-day follow-up.

Regarding new-onset seizures in the general population, there was no statistically significant difference in risk for seizure incidence among vaccinated individuals vs placebo recipients, according to our meta-analysis, wrote the investigators, led by Ali Rafati, MD, MPH, Iran University of Medical Sciences in Tehran.

The findings were published online in JAMA Neurology.

Mixed Results

Results from previous research have been mixed regarding the link between the SARS-CoV-2 vaccination and new-onset seizures, with some showing an association.

To learn more about the possible association between the vaccines and new-onset seizures, the researchers conducted a literature review and identified six RCTs that measured adverse events following SARS-CoV-2 vaccinations (including messenger RNA, viral vector, and inactivated virus) vs placebo or other vaccines.

While five of the studies defined new-onset seizures according to the Medical Dictionary for Regulatory Activities, trial investigators in the sixth RCT assessed and determined new-onset seizures in participants.

Participants received two vaccinations 28 days apart in five RCTs and only one vaccine in the sixth trial.

The research team searched the data for new-onset seizure in the 28 days following one or both COVID vaccinations.

No Link Found

After comparing the incidence of new-onset seizure between the 63,500 vaccine (nine new-onset seizures, 0.014%) and 55,000 placebo recipients (one new-onset seizure, 0.002%), investigators found no significant difference between the two groups (odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12)

Investigators also sliced the data several ways to see if it would yield different results. When they analyzed data by vaccine platform (viral vector) and age group (children), they didn’t observe significant differences in new-onset data.

The researchers also searched for data beyond the month following the injection to encompass the entire blinded phase, so they analyzed the results of three RCTs that reported adverse events up to 162 days after the vaccine.

After pooling the results from the three studies, investigators found no statistical difference between the vaccine and placebo groups in terms of the new-onset seizure (OR, 2.31; 95% CI, 0.86%-3.23; P > .99)

Study limitations included the missing information on vaccine doses or risk factors for the development of seizures. Also, the RCTs included in the meta-analysis were conducted at different times, so the SARS-CoV-2 vaccines may have differed in their composition and efficacy.

“The global vaccination drive against SARS-CoV-2 has been a monumental effort in combating the pandemic. SARS-CoV-2 vaccinations that are now available appear safe and appropriate,” the authors wrote.

There were no study funding sources or disclosures reported.

A version of this article appeared on Medscape.com.

There is no association between the SARS-CoV-2 vaccine and the risk for new-onset seizure, data from a new meta-analysis of six randomized, placebo-controlled clinical trials (RCTs) showed.

Results of the pooled analysis that included 63,500 individuals vaccinated with SARS-CoV-2 and 55,000 who received a placebo vaccine showed there was no significant difference between the two groups with respect to new-onset seizures at 28- or 43-day follow-up.

Regarding new-onset seizures in the general population, there was no statistically significant difference in risk for seizure incidence among vaccinated individuals vs placebo recipients, according to our meta-analysis, wrote the investigators, led by Ali Rafati, MD, MPH, Iran University of Medical Sciences in Tehran.

The findings were published online in JAMA Neurology.

Mixed Results

Results from previous research have been mixed regarding the link between the SARS-CoV-2 vaccination and new-onset seizures, with some showing an association.

To learn more about the possible association between the vaccines and new-onset seizures, the researchers conducted a literature review and identified six RCTs that measured adverse events following SARS-CoV-2 vaccinations (including messenger RNA, viral vector, and inactivated virus) vs placebo or other vaccines.

While five of the studies defined new-onset seizures according to the Medical Dictionary for Regulatory Activities, trial investigators in the sixth RCT assessed and determined new-onset seizures in participants.

Participants received two vaccinations 28 days apart in five RCTs and only one vaccine in the sixth trial.

The research team searched the data for new-onset seizure in the 28 days following one or both COVID vaccinations.

No Link Found

After comparing the incidence of new-onset seizure between the 63,500 vaccine (nine new-onset seizures, 0.014%) and 55,000 placebo recipients (one new-onset seizure, 0.002%), investigators found no significant difference between the two groups (odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12)

Investigators also sliced the data several ways to see if it would yield different results. When they analyzed data by vaccine platform (viral vector) and age group (children), they didn’t observe significant differences in new-onset data.

The researchers also searched for data beyond the month following the injection to encompass the entire blinded phase, so they analyzed the results of three RCTs that reported adverse events up to 162 days after the vaccine.

After pooling the results from the three studies, investigators found no statistical difference between the vaccine and placebo groups in terms of the new-onset seizure (OR, 2.31; 95% CI, 0.86%-3.23; P > .99)

Study limitations included the missing information on vaccine doses or risk factors for the development of seizures. Also, the RCTs included in the meta-analysis were conducted at different times, so the SARS-CoV-2 vaccines may have differed in their composition and efficacy.

“The global vaccination drive against SARS-CoV-2 has been a monumental effort in combating the pandemic. SARS-CoV-2 vaccinations that are now available appear safe and appropriate,” the authors wrote.

There were no study funding sources or disclosures reported.

A version of this article appeared on Medscape.com.

Diagnosis: Venous Malformation

Venous malformations are the most common type of congenital vascular malformation. Although present at birth, they are not always clinically evident early in life. They also tend to grow with the child without spontaneous regression, causing potential cosmetic concerns or complications from impingement on surrounding tissue.

Venous malformations appear with a bluish color appearing beneath the skin and can vary significantly in size and severity. Venous malformations are compressible and characterized by low to stagnant blood flow, which can spontaneously thrombose. Clinically, this may cause pain, swelling, skin changes, tissue and limb overgrowth, or functional impairment depending on location and size.

Dr. Lawence Eichenfield

Treatment

Venous malformations rarely regress spontaneously. Treatment is required if venous malformations are symptomatic, which may include pain, swelling, deformity, thrombosis, or interference with daily activities of living. Treatment plans require consideration of patient goals of care. The main categories of therapy are embolization/sclerotherapy, surgical resection, and molecular targeted therapy.

Sclerotherapy is a well-tolerated and efficacious first-line therapy. It can be used as either nonsurgical curative therapy or preoperative adjunct therapy to minimize blood loss before surgical resection. While surgical resection may cause scarring, multimodal approaches with sclerotherapy or laser therapy can decrease complications. Molecular therapies aim to reduce vascular proliferation and symptoms. Referral to hematology/oncology for evaluation and consideration of chemotherapeutic agents may be required. Sirolimus has been shown in mice models to inhibit an endothelial cell tyrosine kinase receptor that plays a role in venous malformation growth. Multiple studies have proved its efficacy in managing complicated vascular anomalies, including venous malformations. Alpelisib is an inhibitor of PI3KCA, which is part of the pathway that contributes to venous malformation formation. Dactolisib, a dual inhibitor of the PI3KA and mTOR pathways, and rebastinib, a TEK inhibitor, are being investigated.

Differential Diagnoses

The differential diagnosis includes dermal melanocytosis, nevus of Ota, hemangioma of infancy, and ashy dermatosis. In addition, venous malformations can be part of more complex vascular malformations.

Dermal melanocytosis, also known as Mongolian spots, are blue-gray patches of discoloration on the skin that appear at birth or shortly after. They result from the arrest of dermal melanocytes in the dermis during fetal life and tissue modeling. They are commonly observed in those of Asian or African descent with darker skin types. Most often, they are located in the lumbar or sacral-gluteal region. Unlike venous malformations, they are benign and do not involve vascular abnormalities. They typically fade over time.

Courtesy University of California, San Diego

Danny Lee and Samuel Le serve as research fellows and Jolina Bui as research associate in the Pediatric Dermatology Division of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is Distinguished Professor of Dermatology and Pediatrics and Vice-Chair of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. The authors have no relevant financial disclosures.

Suggested Reading

Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls [Internet]. StatPearls Publishing; 2024.

Dompmartin A et al. The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations. J Vasc Anom (Phila). 2023 Mar 23;4(2):e064.

Dompmartin A et al. Venous malformation: Update on aetiopathogenesis, diagnosis and management. Phlebology. 2010 Oct;25(5):224-235.

Gupta D, Thappa DM. Mongolian spots. Indian J Dermatol Venereol Leprol. 2013 Jul-Aug;79(4):469-478.

Krowchuk DP et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan;143(1):e20183475.

Nguyen K, Khachemoune A. Ashy dermatosis: A review. Dermatol Online J. 2019 May 15;25(5):13030/qt44f462s8.

Patel ND, Chong AT et al. Venous Malformations. Semin Intervent Radiol. 2022 Dec 20;39(5):498-507.

Diagnosis: Venous Malformation

Venous malformations are the most common type of congenital vascular malformation. Although present at birth, they are not always clinically evident early in life. They also tend to grow with the child without spontaneous regression, causing potential cosmetic concerns or complications from impingement on surrounding tissue.

Venous malformations appear with a bluish color appearing beneath the skin and can vary significantly in size and severity. Venous malformations are compressible and characterized by low to stagnant blood flow, which can spontaneously thrombose. Clinically, this may cause pain, swelling, skin changes, tissue and limb overgrowth, or functional impairment depending on location and size.

Dr. Lawence Eichenfield

Treatment

Venous malformations rarely regress spontaneously. Treatment is required if venous malformations are symptomatic, which may include pain, swelling, deformity, thrombosis, or interference with daily activities of living. Treatment plans require consideration of patient goals of care. The main categories of therapy are embolization/sclerotherapy, surgical resection, and molecular targeted therapy.

Sclerotherapy is a well-tolerated and efficacious first-line therapy. It can be used as either nonsurgical curative therapy or preoperative adjunct therapy to minimize blood loss before surgical resection. While surgical resection may cause scarring, multimodal approaches with sclerotherapy or laser therapy can decrease complications. Molecular therapies aim to reduce vascular proliferation and symptoms. Referral to hematology/oncology for evaluation and consideration of chemotherapeutic agents may be required. Sirolimus has been shown in mice models to inhibit an endothelial cell tyrosine kinase receptor that plays a role in venous malformation growth. Multiple studies have proved its efficacy in managing complicated vascular anomalies, including venous malformations. Alpelisib is an inhibitor of PI3KCA, which is part of the pathway that contributes to venous malformation formation. Dactolisib, a dual inhibitor of the PI3KA and mTOR pathways, and rebastinib, a TEK inhibitor, are being investigated.

Differential Diagnoses

The differential diagnosis includes dermal melanocytosis, nevus of Ota, hemangioma of infancy, and ashy dermatosis. In addition, venous malformations can be part of more complex vascular malformations.

Dermal melanocytosis, also known as Mongolian spots, are blue-gray patches of discoloration on the skin that appear at birth or shortly after. They result from the arrest of dermal melanocytes in the dermis during fetal life and tissue modeling. They are commonly observed in those of Asian or African descent with darker skin types. Most often, they are located in the lumbar or sacral-gluteal region. Unlike venous malformations, they are benign and do not involve vascular abnormalities. They typically fade over time.

Courtesy University of California, San Diego

Danny Lee and Samuel Le serve as research fellows and Jolina Bui as research associate in the Pediatric Dermatology Division of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is Distinguished Professor of Dermatology and Pediatrics and Vice-Chair of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. The authors have no relevant financial disclosures.

Suggested Reading

Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls [Internet]. StatPearls Publishing; 2024.

Dompmartin A et al. The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations. J Vasc Anom (Phila). 2023 Mar 23;4(2):e064.

Dompmartin A et al. Venous malformation: Update on aetiopathogenesis, diagnosis and management. Phlebology. 2010 Oct;25(5):224-235.

Gupta D, Thappa DM. Mongolian spots. Indian J Dermatol Venereol Leprol. 2013 Jul-Aug;79(4):469-478.

Krowchuk DP et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan;143(1):e20183475.

Nguyen K, Khachemoune A. Ashy dermatosis: A review. Dermatol Online J. 2019 May 15;25(5):13030/qt44f462s8.

Patel ND, Chong AT et al. Venous Malformations. Semin Intervent Radiol. 2022 Dec 20;39(5):498-507.

Diagnosis: Venous Malformation

Venous malformations are the most common type of congenital vascular malformation. Although present at birth, they are not always clinically evident early in life. They also tend to grow with the child without spontaneous regression, causing potential cosmetic concerns or complications from impingement on surrounding tissue.

Venous malformations appear with a bluish color appearing beneath the skin and can vary significantly in size and severity. Venous malformations are compressible and characterized by low to stagnant blood flow, which can spontaneously thrombose. Clinically, this may cause pain, swelling, skin changes, tissue and limb overgrowth, or functional impairment depending on location and size.

Dr. Lawence Eichenfield

Treatment

Venous malformations rarely regress spontaneously. Treatment is required if venous malformations are symptomatic, which may include pain, swelling, deformity, thrombosis, or interference with daily activities of living. Treatment plans require consideration of patient goals of care. The main categories of therapy are embolization/sclerotherapy, surgical resection, and molecular targeted therapy.

Sclerotherapy is a well-tolerated and efficacious first-line therapy. It can be used as either nonsurgical curative therapy or preoperative adjunct therapy to minimize blood loss before surgical resection. While surgical resection may cause scarring, multimodal approaches with sclerotherapy or laser therapy can decrease complications. Molecular therapies aim to reduce vascular proliferation and symptoms. Referral to hematology/oncology for evaluation and consideration of chemotherapeutic agents may be required. Sirolimus has been shown in mice models to inhibit an endothelial cell tyrosine kinase receptor that plays a role in venous malformation growth. Multiple studies have proved its efficacy in managing complicated vascular anomalies, including venous malformations. Alpelisib is an inhibitor of PI3KCA, which is part of the pathway that contributes to venous malformation formation. Dactolisib, a dual inhibitor of the PI3KA and mTOR pathways, and rebastinib, a TEK inhibitor, are being investigated.

Differential Diagnoses

The differential diagnosis includes dermal melanocytosis, nevus of Ota, hemangioma of infancy, and ashy dermatosis. In addition, venous malformations can be part of more complex vascular malformations.

Dermal melanocytosis, also known as Mongolian spots, are blue-gray patches of discoloration on the skin that appear at birth or shortly after. They result from the arrest of dermal melanocytes in the dermis during fetal life and tissue modeling. They are commonly observed in those of Asian or African descent with darker skin types. Most often, they are located in the lumbar or sacral-gluteal region. Unlike venous malformations, they are benign and do not involve vascular abnormalities. They typically fade over time.

Courtesy University of California, San Diego

Danny Lee and Samuel Le serve as research fellows and Jolina Bui as research associate in the Pediatric Dermatology Division of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is Distinguished Professor of Dermatology and Pediatrics and Vice-Chair of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. The authors have no relevant financial disclosures.

Suggested Reading

Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls [Internet]. StatPearls Publishing; 2024.

Dompmartin A et al. The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations. J Vasc Anom (Phila). 2023 Mar 23;4(2):e064.

Dompmartin A et al. Venous malformation: Update on aetiopathogenesis, diagnosis and management. Phlebology. 2010 Oct;25(5):224-235.

Gupta D, Thappa DM. Mongolian spots. Indian J Dermatol Venereol Leprol. 2013 Jul-Aug;79(4):469-478.

Krowchuk DP et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan;143(1):e20183475.

Nguyen K, Khachemoune A. Ashy dermatosis: A review. Dermatol Online J. 2019 May 15;25(5):13030/qt44f462s8.

Patel ND, Chong AT et al. Venous Malformations. Semin Intervent Radiol. 2022 Dec 20;39(5):498-507.

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

A version of this article first appeared on Medscape.com.

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

A version of this article first appeared on Medscape.com.

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

A version of this article first appeared on Medscape.com.

An evolving legal landscape surrounding medication abortion has left physicians with as many questions as patients. A panel of clinicians at the annual meeting of the American College of Physicians offered guidance on how to help patients who choose medication abortion, which is available to women until 10 weeks of gestation.

Approved in 2000, abortion pills have become the most common method for terminating pregnancy in the United States, accounting for 63% of all abortions in 2023. The US Supreme Court is reviewing access to medication abortions, with a decision expected within months.

According to the Guttmacher Institute, 29 states as of February restrict access to medication abortion, either by limiting or banning the use of the drugs or by curtailing who can prescribe them and under what circumstances.
 

First, Determine Gestational Age

Cynthia Chuang, MD, MSc, an internist and professor of medicine at Penn State College of Medicine in Hershey, Pennsylvania, said in most cases, a woman can pinpoint the date of the first day of her last menstrual period, and the physician can confirm gestational age is 70 days or less. An ultrasound should be performed if the date of the last period is uncertain, she said, or if ectopic pregnancy is suspected, periods are irregular, or ultrasound is legally required in the state.

Women are not eligible for abortion pills if they have a bleeding or clotting disorder, have an intrauterine device, have adrenal insufficiency or chronic steroid use, or have porphyria or hemoglobin levels < 9 g/dL, she said.

“If the person has a known hemoglobin of less than 9, we would suggest that person have a procedural abortion,” Dr. Chuang said.
 

Components of Medication

Patients first receive 200 mg of oral mifepristone, which separates the pregnancy from the uterine wall. “Typically, people don’t experience side effects from the mifepristone alone,” Dr. Chaung said.

In the next 48 hours, the patient takes 800 mcg of misoprostol, either vaginally or buccally. “Patients can expect heavy cramping and bleeding 1-2 days after taking misoprostol,” she said. The bleeding should gradually subside over the following week or 2, she said. If the gestational age is 9 weeks or more, a second dose of misoprostol can be administered 3-6 hours after the first dose to improve efficacy.

If mifepristone is not available, misoprostol can be used alone in three doses spaced 3 hours apart, Dr. Chuang said.

The failure rate for mifepristone plus misoprostol has been calculated at 2% if the gestational age is less than 7 weeks. For misoprostol alone, the failure rate varies by the study, depending on gestational age and population analyzed, Dr. Chuang said. A 2023 meta-analysis in Contraception put the failure rate at 11%.
 

When to Call the Clinician

Dr. Chuang said clinicians should instruct women who have taken abortion pills to call the clinic if they are soaking through two sanitary pads an hour for more than 1 hour, if there is little to no bleeding, or if they think the medication isn’t working after taking the full regimen.

Mindy Sobota, MD, MS, an internist and associate professor of medicine at the Warren Alpert Medical School of Brown University in Providence, Rhode Island, recommended a continuing medical education site for evidence-based guidance on how best to talk with women about medication abortions.

She also recommended physicians and patients consult the Plan C website for guidance on telehealth services and price information on receiving abortion pills by mail in every state. “It’s a very reliable and safe clearing house,” Dr. Sobota said.

Internists should let patients know that whatever their choices are around pregnancy, they are open to discussing those choices and helping them through the process, Dr. Sobota said, adding that she makes those statements in annual visits.

Alexandra Bachorik, MD, EdM, director of education in the Women’s Health Unit and assistant professor of medicine at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, said patients in restrictive states who need financial help related to obtaining abortion services in a less restricted state can visit the National Network of Abortion Funds, which can help people with travel or housing expenses.

Facilitating access to a clinic in a less restrictive state may be helpful to people approaching a gestational age limit, she said.

Adelaide McClintock, MD, an internist and assistant professor of general internal medicine at the University of Washington School of Medicine in Seattle, Washington, noted that even clinicians who cannot legally prescribe abortion pills can support their patients by providing resources and counseling on options before, during, and after pregnancy. Those who live in restrictive states also can provide support to women who have traveled to less restrictive states for an abortion if they have postabortion complications, she said.

She recommended the Reproductive Health Access Project website for a comprehensive guide for evidence-based care and counseling patients about all choices in reproductive healthcare.

Panelists urged clinicians to get familiar with abortion-access resources and keep them at their fingertips in practice. Patient requests for the services are common, she noted, as “one in four women will have an abortion by the age of 45.”

Dr. Chuang, Dr. McClintock, Dr. Sobota, and Dr. Bachorik reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

An evolving legal landscape surrounding medication abortion has left physicians with as many questions as patients. A panel of clinicians at the annual meeting of the American College of Physicians offered guidance on how to help patients who choose medication abortion, which is available to women until 10 weeks of gestation.

Approved in 2000, abortion pills have become the most common method for terminating pregnancy in the United States, accounting for 63% of all abortions in 2023. The US Supreme Court is reviewing access to medication abortions, with a decision expected within months.

According to the Guttmacher Institute, 29 states as of February restrict access to medication abortion, either by limiting or banning the use of the drugs or by curtailing who can prescribe them and under what circumstances.
 

First, Determine Gestational Age

Cynthia Chuang, MD, MSc, an internist and professor of medicine at Penn State College of Medicine in Hershey, Pennsylvania, said in most cases, a woman can pinpoint the date of the first day of her last menstrual period, and the physician can confirm gestational age is 70 days or less. An ultrasound should be performed if the date of the last period is uncertain, she said, or if ectopic pregnancy is suspected, periods are irregular, or ultrasound is legally required in the state.

Women are not eligible for abortion pills if they have a bleeding or clotting disorder, have an intrauterine device, have adrenal insufficiency or chronic steroid use, or have porphyria or hemoglobin levels < 9 g/dL, she said.

“If the person has a known hemoglobin of less than 9, we would suggest that person have a procedural abortion,” Dr. Chuang said.
 

Components of Medication

Patients first receive 200 mg of oral mifepristone, which separates the pregnancy from the uterine wall. “Typically, people don’t experience side effects from the mifepristone alone,” Dr. Chaung said.

In the next 48 hours, the patient takes 800 mcg of misoprostol, either vaginally or buccally. “Patients can expect heavy cramping and bleeding 1-2 days after taking misoprostol,” she said. The bleeding should gradually subside over the following week or 2, she said. If the gestational age is 9 weeks or more, a second dose of misoprostol can be administered 3-6 hours after the first dose to improve efficacy.

If mifepristone is not available, misoprostol can be used alone in three doses spaced 3 hours apart, Dr. Chuang said.

The failure rate for mifepristone plus misoprostol has been calculated at 2% if the gestational age is less than 7 weeks. For misoprostol alone, the failure rate varies by the study, depending on gestational age and population analyzed, Dr. Chuang said. A 2023 meta-analysis in Contraception put the failure rate at 11%.
 

When to Call the Clinician

Dr. Chuang said clinicians should instruct women who have taken abortion pills to call the clinic if they are soaking through two sanitary pads an hour for more than 1 hour, if there is little to no bleeding, or if they think the medication isn’t working after taking the full regimen.

Mindy Sobota, MD, MS, an internist and associate professor of medicine at the Warren Alpert Medical School of Brown University in Providence, Rhode Island, recommended a continuing medical education site for evidence-based guidance on how best to talk with women about medication abortions.

She also recommended physicians and patients consult the Plan C website for guidance on telehealth services and price information on receiving abortion pills by mail in every state. “It’s a very reliable and safe clearing house,” Dr. Sobota said.

Internists should let patients know that whatever their choices are around pregnancy, they are open to discussing those choices and helping them through the process, Dr. Sobota said, adding that she makes those statements in annual visits.

Alexandra Bachorik, MD, EdM, director of education in the Women’s Health Unit and assistant professor of medicine at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, said patients in restrictive states who need financial help related to obtaining abortion services in a less restricted state can visit the National Network of Abortion Funds, which can help people with travel or housing expenses.

Facilitating access to a clinic in a less restrictive state may be helpful to people approaching a gestational age limit, she said.

Adelaide McClintock, MD, an internist and assistant professor of general internal medicine at the University of Washington School of Medicine in Seattle, Washington, noted that even clinicians who cannot legally prescribe abortion pills can support their patients by providing resources and counseling on options before, during, and after pregnancy. Those who live in restrictive states also can provide support to women who have traveled to less restrictive states for an abortion if they have postabortion complications, she said.

She recommended the Reproductive Health Access Project website for a comprehensive guide for evidence-based care and counseling patients about all choices in reproductive healthcare.

Panelists urged clinicians to get familiar with abortion-access resources and keep them at their fingertips in practice. Patient requests for the services are common, she noted, as “one in four women will have an abortion by the age of 45.”

Dr. Chuang, Dr. McClintock, Dr. Sobota, and Dr. Bachorik reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

An evolving legal landscape surrounding medication abortion has left physicians with as many questions as patients. A panel of clinicians at the annual meeting of the American College of Physicians offered guidance on how to help patients who choose medication abortion, which is available to women until 10 weeks of gestation.

Approved in 2000, abortion pills have become the most common method for terminating pregnancy in the United States, accounting for 63% of all abortions in 2023. The US Supreme Court is reviewing access to medication abortions, with a decision expected within months.

According to the Guttmacher Institute, 29 states as of February restrict access to medication abortion, either by limiting or banning the use of the drugs or by curtailing who can prescribe them and under what circumstances.
 

First, Determine Gestational Age

Cynthia Chuang, MD, MSc, an internist and professor of medicine at Penn State College of Medicine in Hershey, Pennsylvania, said in most cases, a woman can pinpoint the date of the first day of her last menstrual period, and the physician can confirm gestational age is 70 days or less. An ultrasound should be performed if the date of the last period is uncertain, she said, or if ectopic pregnancy is suspected, periods are irregular, or ultrasound is legally required in the state.

Women are not eligible for abortion pills if they have a bleeding or clotting disorder, have an intrauterine device, have adrenal insufficiency or chronic steroid use, or have porphyria or hemoglobin levels < 9 g/dL, she said.

“If the person has a known hemoglobin of less than 9, we would suggest that person have a procedural abortion,” Dr. Chuang said.
 

Components of Medication

Patients first receive 200 mg of oral mifepristone, which separates the pregnancy from the uterine wall. “Typically, people don’t experience side effects from the mifepristone alone,” Dr. Chaung said.

In the next 48 hours, the patient takes 800 mcg of misoprostol, either vaginally or buccally. “Patients can expect heavy cramping and bleeding 1-2 days after taking misoprostol,” she said. The bleeding should gradually subside over the following week or 2, she said. If the gestational age is 9 weeks or more, a second dose of misoprostol can be administered 3-6 hours after the first dose to improve efficacy.

If mifepristone is not available, misoprostol can be used alone in three doses spaced 3 hours apart, Dr. Chuang said.

The failure rate for mifepristone plus misoprostol has been calculated at 2% if the gestational age is less than 7 weeks. For misoprostol alone, the failure rate varies by the study, depending on gestational age and population analyzed, Dr. Chuang said. A 2023 meta-analysis in Contraception put the failure rate at 11%.
 

When to Call the Clinician

Dr. Chuang said clinicians should instruct women who have taken abortion pills to call the clinic if they are soaking through two sanitary pads an hour for more than 1 hour, if there is little to no bleeding, or if they think the medication isn’t working after taking the full regimen.

Mindy Sobota, MD, MS, an internist and associate professor of medicine at the Warren Alpert Medical School of Brown University in Providence, Rhode Island, recommended a continuing medical education site for evidence-based guidance on how best to talk with women about medication abortions.

She also recommended physicians and patients consult the Plan C website for guidance on telehealth services and price information on receiving abortion pills by mail in every state. “It’s a very reliable and safe clearing house,” Dr. Sobota said.

Internists should let patients know that whatever their choices are around pregnancy, they are open to discussing those choices and helping them through the process, Dr. Sobota said, adding that she makes those statements in annual visits.

Alexandra Bachorik, MD, EdM, director of education in the Women’s Health Unit and assistant professor of medicine at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, said patients in restrictive states who need financial help related to obtaining abortion services in a less restricted state can visit the National Network of Abortion Funds, which can help people with travel or housing expenses.

Facilitating access to a clinic in a less restrictive state may be helpful to people approaching a gestational age limit, she said.

Adelaide McClintock, MD, an internist and assistant professor of general internal medicine at the University of Washington School of Medicine in Seattle, Washington, noted that even clinicians who cannot legally prescribe abortion pills can support their patients by providing resources and counseling on options before, during, and after pregnancy. Those who live in restrictive states also can provide support to women who have traveled to less restrictive states for an abortion if they have postabortion complications, she said.

She recommended the Reproductive Health Access Project website for a comprehensive guide for evidence-based care and counseling patients about all choices in reproductive healthcare.

Panelists urged clinicians to get familiar with abortion-access resources and keep them at their fingertips in practice. Patient requests for the services are common, she noted, as “one in four women will have an abortion by the age of 45.”

Dr. Chuang, Dr. McClintock, Dr. Sobota, and Dr. Bachorik reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

An experimental handheld ultrasonic device used in an office setting was shown to guide residual kidney stone fragments out of the body and markedly reduce the risk for relapse, researchers reported (Abstract MP29-10) at the 2024 annual meeting of the American Urological Association AUA in San Antonio, Texas.

Mathew Sorensen, MD, MS, an associate professor of urology at the University of Washington, Seattle, and director of the Comprehensive Metabolic Stone Clinic at the Puget Sound VA, said that the risk for relapse of kidney stones was 70% lower in the treatment group than in the control group.

“This is an ultrasound-based propulsion procedure that is not like anything else that has ever existed. There’s nothing else that’s like it,” Dr. Sorensen said. “Essentially, in a session in the office with no anesthesia, we can use ultrasound energy to focus on those fragments and try to push them out of the unfavorable areas of the kidney.”

Roughly 20%-30% of patients who undergo surgery to remove kidney stones have residual fragments that can ultimately cause pain and send them to the emergency department or into hospital admission for treatment.

In the new study, 82 patients with stone fragments ≤ 5 mm were randomly assigned to receive the ultrasound treatment — which Dr. Sorensen and his colleagues developed over the past decade — or no procedure.

During a median follow-up of 2.6 years, 20% of patients in the treatment group experienced relapse of stones compared with 50% of patients in the control group. 

Relapse was measured as the future occurrence of urgent medical visits for stone-related symptoms, surgeries, or growth of the residual fragments as measured on annual CT.

Dr. Sorensen and his colleagues found asymptomatic passage of fragments was twelvefold higher in the treatment group in the first 3 weeks (60% vs 5%). Asymptomatic passage was similar in both groups after 3 weeks.

Dr. Sorensen said that mild discomfort after the procedure was common, occurring in 38% of patients who underwent the treatment, but that it was short-lived and resolved without intervention; 8% of the treatment group and 7% of the control group had blood in the urine.

The propulsion device is available at two test sites in the University of Washington system; the manufacturer, SonoMotion Inc, a spinoff from the institution, is seeking US Food and Drug Administration approval for the technology, Dr. Sorensen said. 

David Schulsinger, MD, an associate professor in the Department of Urology at Stony Brook University Hospital, Stony Brook, New York, said that patients with stone fragments currently have two options: follow-up surgery or active surveillance.

“With this new device, we actually have the potential for doing one other thing, and that is treating these patients noninvasively and without anesthesia,” Dr. Schulsinger said. “Once it’s ready for prime time, I think [ultrasonic propulsion] will be very well accepted among urologists to manage patients with asymptomatic residual stones.”

Dr. Sorensen is an advisor and equity holder in SonoMotion Inc. Dr. Schulsinger reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

An experimental handheld ultrasonic device used in an office setting was shown to guide residual kidney stone fragments out of the body and markedly reduce the risk for relapse, researchers reported (Abstract MP29-10) at the 2024 annual meeting of the American Urological Association AUA in San Antonio, Texas.

Mathew Sorensen, MD, MS, an associate professor of urology at the University of Washington, Seattle, and director of the Comprehensive Metabolic Stone Clinic at the Puget Sound VA, said that the risk for relapse of kidney stones was 70% lower in the treatment group than in the control group.

“This is an ultrasound-based propulsion procedure that is not like anything else that has ever existed. There’s nothing else that’s like it,” Dr. Sorensen said. “Essentially, in a session in the office with no anesthesia, we can use ultrasound energy to focus on those fragments and try to push them out of the unfavorable areas of the kidney.”

Roughly 20%-30% of patients who undergo surgery to remove kidney stones have residual fragments that can ultimately cause pain and send them to the emergency department or into hospital admission for treatment.

In the new study, 82 patients with stone fragments ≤ 5 mm were randomly assigned to receive the ultrasound treatment — which Dr. Sorensen and his colleagues developed over the past decade — or no procedure.

During a median follow-up of 2.6 years, 20% of patients in the treatment group experienced relapse of stones compared with 50% of patients in the control group. 

Relapse was measured as the future occurrence of urgent medical visits for stone-related symptoms, surgeries, or growth of the residual fragments as measured on annual CT.

Dr. Sorensen and his colleagues found asymptomatic passage of fragments was twelvefold higher in the treatment group in the first 3 weeks (60% vs 5%). Asymptomatic passage was similar in both groups after 3 weeks.

Dr. Sorensen said that mild discomfort after the procedure was common, occurring in 38% of patients who underwent the treatment, but that it was short-lived and resolved without intervention; 8% of the treatment group and 7% of the control group had blood in the urine.

The propulsion device is available at two test sites in the University of Washington system; the manufacturer, SonoMotion Inc, a spinoff from the institution, is seeking US Food and Drug Administration approval for the technology, Dr. Sorensen said. 

David Schulsinger, MD, an associate professor in the Department of Urology at Stony Brook University Hospital, Stony Brook, New York, said that patients with stone fragments currently have two options: follow-up surgery or active surveillance.

“With this new device, we actually have the potential for doing one other thing, and that is treating these patients noninvasively and without anesthesia,” Dr. Schulsinger said. “Once it’s ready for prime time, I think [ultrasonic propulsion] will be very well accepted among urologists to manage patients with asymptomatic residual stones.”

Dr. Sorensen is an advisor and equity holder in SonoMotion Inc. Dr. Schulsinger reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

An experimental handheld ultrasonic device used in an office setting was shown to guide residual kidney stone fragments out of the body and markedly reduce the risk for relapse, researchers reported (Abstract MP29-10) at the 2024 annual meeting of the American Urological Association AUA in San Antonio, Texas.

Mathew Sorensen, MD, MS, an associate professor of urology at the University of Washington, Seattle, and director of the Comprehensive Metabolic Stone Clinic at the Puget Sound VA, said that the risk for relapse of kidney stones was 70% lower in the treatment group than in the control group.

“This is an ultrasound-based propulsion procedure that is not like anything else that has ever existed. There’s nothing else that’s like it,” Dr. Sorensen said. “Essentially, in a session in the office with no anesthesia, we can use ultrasound energy to focus on those fragments and try to push them out of the unfavorable areas of the kidney.”

Roughly 20%-30% of patients who undergo surgery to remove kidney stones have residual fragments that can ultimately cause pain and send them to the emergency department or into hospital admission for treatment.

In the new study, 82 patients with stone fragments ≤ 5 mm were randomly assigned to receive the ultrasound treatment — which Dr. Sorensen and his colleagues developed over the past decade — or no procedure.

During a median follow-up of 2.6 years, 20% of patients in the treatment group experienced relapse of stones compared with 50% of patients in the control group. 

Relapse was measured as the future occurrence of urgent medical visits for stone-related symptoms, surgeries, or growth of the residual fragments as measured on annual CT.

Dr. Sorensen and his colleagues found asymptomatic passage of fragments was twelvefold higher in the treatment group in the first 3 weeks (60% vs 5%). Asymptomatic passage was similar in both groups after 3 weeks.

Dr. Sorensen said that mild discomfort after the procedure was common, occurring in 38% of patients who underwent the treatment, but that it was short-lived and resolved without intervention; 8% of the treatment group and 7% of the control group had blood in the urine.

The propulsion device is available at two test sites in the University of Washington system; the manufacturer, SonoMotion Inc, a spinoff from the institution, is seeking US Food and Drug Administration approval for the technology, Dr. Sorensen said. 

David Schulsinger, MD, an associate professor in the Department of Urology at Stony Brook University Hospital, Stony Brook, New York, said that patients with stone fragments currently have two options: follow-up surgery or active surveillance.

“With this new device, we actually have the potential for doing one other thing, and that is treating these patients noninvasively and without anesthesia,” Dr. Schulsinger said. “Once it’s ready for prime time, I think [ultrasonic propulsion] will be very well accepted among urologists to manage patients with asymptomatic residual stones.”

Dr. Sorensen is an advisor and equity holder in SonoMotion Inc. Dr. Schulsinger reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.