The most important study from ESC: FRAIL-AF

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Changed
Tue, 09/05/2023 - 13:15

 

One of the hardest tasks of a clinician is applying evidence from trials to the person in your office. At the annual congress of the European Society of Cardiology, the surprising and unexpected results of the FRAIL-AF trial confirm the massive challenge of evidence translation.

FRAIL-AF investigators set out to study the question of whether frail, elderly patients with atrial fibrillation who were doing well with vitamin K antagonists (VKA) should be switched to direct-acting oral anticoagulants (DOAC).

Senior author Geert-Jan Geersing, MD, PhD, from the University Medical Center Utrecht (the Netherlands), told me that frustration led him to design this study. He was frustrated that colleagues assumed that evidence in nonfrail patients can always be translated to frail patients. 

Dr. Geersing offered two reasons why common wisdom may be wrong. First was that the large DOAC versus warfarin trials included few elderly patients with frailty. Second, first author Linda Joosten, MD, made it clear in her presentation that frailty is a lot more than aging. It is a clinical syndrome, which entails a “high burden of comorbidities, dependency on others, and a reduced ability to resist stressors.”
 

The FRAIL-AF trial

The investigators recruited elderly, frail patients with fibrillation who were treated with VKAs and had stable international normalized ratios from outpatient clinics throughout the Netherlands. They screened about 2,600 patients and enrolled nearly 1,400. Most were excluded for not being frail.

Half the group was randomized to switching to a DOAC – drug choice was left to the treating clinician – and the other half remained on VKAs. Patients were 83 years of age on average with a mean CHA2DS2-VASc score of 4. All four classes of DOAC were used in the switching arm.

The primary endpoint was major or clinically relevant nonmajor bleeding, whichever came first, accounting for death as a competing risk. Follow-up was 1 year.
 

The results for switching to DOAC vs. VKA

Dr. Joosten started her presentation with this: “The results turned out to be different than we expected.” The authors designed the trial with the idea that switching to DOACs would be superior in safety to remaining on VKAs.

But the trial was halted after an interim analysis found a rate of major bleeding in the switching arm of 15.3% versus 9.4% in the arm staying on VKA (hazard ratio, 1.69; 95% confidence interval, 1.23-2.32; P = .0012).

The Kaplan-Meier event curves reveal that the excess risk of bleeding occurred after 100 days and increased with time. This argued against an early effect from transitioning the drugs.

An analysis looking at specific DOAC drugs revealed similar hazards for the two most common ones used – apixaban and rivaroxaban.

Thrombotic events were a secondary endpoint and were low in absolute numbers, 2.4% versus 2.0%, for remaining on VKA and switching to DOAC, respectively (HR, 1.26; 95% CI, 0.60-2.61).

The time in therapeutic range in FRAIL-AF was similar to that in the seminal DOAC trials.
 

Comments

Three reasons lead me to choose FRAIL-AF as the most important study from the 2023 ESC congress.

First is the specific lesson about switching drugs. Note that FRAIL-AF did not address the question of starting anticoagulation. The trial results show that if you have a frail older patient who is doing well on VKA, don’t change to a DOAC. That is important to know, but it is not what gives this study its heft.

The second reason centers on the investigators choice to do this trial. Dr. Geersing had a feeling that common wisdom was wrong. He did not try to persuade colleagues with anecdote or plausibility or meta-analyses of observational studies. He set out to answer a question in the correct way – with a randomized trial.

This is the path forward in medicine. I’ve often heard proponents of observational research declare that many topics in medicine cannot be studied with trials. I could hear people arguing that it’s not feasible to study mostly home-bound, elderly frail patients. And the fact that there exist so few trials in this space would support that argument.

But the FRAIL-AF authors showed that it is possible. This is the kind of science that medicine should celebrate. There were no soft endpoints, financial conflicts, or spin. If medical science had science as its incentive, rather than attention, FRAIL-AF easily wins top honors.

The third reason FRAIL-AF is so important is that it teaches us the humility required in translating evidence in our clinics. I like to say evidence is what separates doctors from palm readers. But using this evidence requires thinking hard about how average effects in trial environments apply to our patient.

Yes, of course, there is clear evidence from tens of thousands of patients in the DOAC versus warfarin trials, that, for those patients, on average, DOACs compare favorably with VKA. The average age of patients in these trials was 70-73 years; the average age in FRAIL-AF was 83 years. And that is just age. A substudy of the ENGAGE AF-TIMI 48 trial found that only 360 of more than 20,000 patients in the trial had severe frailty.

FRAIL-AF clearly shows how cautious we should be in applying evidence gathered in younger, healthier patients to older, more vulnerable patients. That lesson extends to nearly every common therapy in medicine today. It also casts great doubt on the soft-thinking idea of using evidence from trials to derive quality metrics. As if the nuance of evidence translation can be captured in an electronic health record.

The skillful use of evidence will be one of the main challenges of the next generation of clinicians. Thanks to advances in medical science, more patients will live long enough to become frail. And the so-called “guideline-directed” therapies may not apply to them.

Dr. Joosten, Dr. Geersing, and the FRAIL-AF team have taught us specific lessons about anticoagulation, but their greatest contribution has been to demonstrate the value of humility in science and the practice of evidence-based medicine.

If you treat patients, no trial at this meeting is more important.

Dr. Mandrola is a clinical electrophysiologist at Baptist Medical Associates, Louisville, Ky. He reported no relevant conflicts of interest.
 

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

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One of the hardest tasks of a clinician is applying evidence from trials to the person in your office. At the annual congress of the European Society of Cardiology, the surprising and unexpected results of the FRAIL-AF trial confirm the massive challenge of evidence translation.

FRAIL-AF investigators set out to study the question of whether frail, elderly patients with atrial fibrillation who were doing well with vitamin K antagonists (VKA) should be switched to direct-acting oral anticoagulants (DOAC).

Senior author Geert-Jan Geersing, MD, PhD, from the University Medical Center Utrecht (the Netherlands), told me that frustration led him to design this study. He was frustrated that colleagues assumed that evidence in nonfrail patients can always be translated to frail patients. 

Dr. Geersing offered two reasons why common wisdom may be wrong. First was that the large DOAC versus warfarin trials included few elderly patients with frailty. Second, first author Linda Joosten, MD, made it clear in her presentation that frailty is a lot more than aging. It is a clinical syndrome, which entails a “high burden of comorbidities, dependency on others, and a reduced ability to resist stressors.”
 

The FRAIL-AF trial

The investigators recruited elderly, frail patients with fibrillation who were treated with VKAs and had stable international normalized ratios from outpatient clinics throughout the Netherlands. They screened about 2,600 patients and enrolled nearly 1,400. Most were excluded for not being frail.

Half the group was randomized to switching to a DOAC – drug choice was left to the treating clinician – and the other half remained on VKAs. Patients were 83 years of age on average with a mean CHA2DS2-VASc score of 4. All four classes of DOAC were used in the switching arm.

The primary endpoint was major or clinically relevant nonmajor bleeding, whichever came first, accounting for death as a competing risk. Follow-up was 1 year.
 

The results for switching to DOAC vs. VKA

Dr. Joosten started her presentation with this: “The results turned out to be different than we expected.” The authors designed the trial with the idea that switching to DOACs would be superior in safety to remaining on VKAs.

But the trial was halted after an interim analysis found a rate of major bleeding in the switching arm of 15.3% versus 9.4% in the arm staying on VKA (hazard ratio, 1.69; 95% confidence interval, 1.23-2.32; P = .0012).

The Kaplan-Meier event curves reveal that the excess risk of bleeding occurred after 100 days and increased with time. This argued against an early effect from transitioning the drugs.

An analysis looking at specific DOAC drugs revealed similar hazards for the two most common ones used – apixaban and rivaroxaban.

Thrombotic events were a secondary endpoint and were low in absolute numbers, 2.4% versus 2.0%, for remaining on VKA and switching to DOAC, respectively (HR, 1.26; 95% CI, 0.60-2.61).

The time in therapeutic range in FRAIL-AF was similar to that in the seminal DOAC trials.
 

Comments

Three reasons lead me to choose FRAIL-AF as the most important study from the 2023 ESC congress.

First is the specific lesson about switching drugs. Note that FRAIL-AF did not address the question of starting anticoagulation. The trial results show that if you have a frail older patient who is doing well on VKA, don’t change to a DOAC. That is important to know, but it is not what gives this study its heft.

The second reason centers on the investigators choice to do this trial. Dr. Geersing had a feeling that common wisdom was wrong. He did not try to persuade colleagues with anecdote or plausibility or meta-analyses of observational studies. He set out to answer a question in the correct way – with a randomized trial.

This is the path forward in medicine. I’ve often heard proponents of observational research declare that many topics in medicine cannot be studied with trials. I could hear people arguing that it’s not feasible to study mostly home-bound, elderly frail patients. And the fact that there exist so few trials in this space would support that argument.

But the FRAIL-AF authors showed that it is possible. This is the kind of science that medicine should celebrate. There were no soft endpoints, financial conflicts, or spin. If medical science had science as its incentive, rather than attention, FRAIL-AF easily wins top honors.

The third reason FRAIL-AF is so important is that it teaches us the humility required in translating evidence in our clinics. I like to say evidence is what separates doctors from palm readers. But using this evidence requires thinking hard about how average effects in trial environments apply to our patient.

Yes, of course, there is clear evidence from tens of thousands of patients in the DOAC versus warfarin trials, that, for those patients, on average, DOACs compare favorably with VKA. The average age of patients in these trials was 70-73 years; the average age in FRAIL-AF was 83 years. And that is just age. A substudy of the ENGAGE AF-TIMI 48 trial found that only 360 of more than 20,000 patients in the trial had severe frailty.

FRAIL-AF clearly shows how cautious we should be in applying evidence gathered in younger, healthier patients to older, more vulnerable patients. That lesson extends to nearly every common therapy in medicine today. It also casts great doubt on the soft-thinking idea of using evidence from trials to derive quality metrics. As if the nuance of evidence translation can be captured in an electronic health record.

The skillful use of evidence will be one of the main challenges of the next generation of clinicians. Thanks to advances in medical science, more patients will live long enough to become frail. And the so-called “guideline-directed” therapies may not apply to them.

Dr. Joosten, Dr. Geersing, and the FRAIL-AF team have taught us specific lessons about anticoagulation, but their greatest contribution has been to demonstrate the value of humility in science and the practice of evidence-based medicine.

If you treat patients, no trial at this meeting is more important.

Dr. Mandrola is a clinical electrophysiologist at Baptist Medical Associates, Louisville, Ky. He reported no relevant conflicts of interest.
 

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

 

One of the hardest tasks of a clinician is applying evidence from trials to the person in your office. At the annual congress of the European Society of Cardiology, the surprising and unexpected results of the FRAIL-AF trial confirm the massive challenge of evidence translation.

FRAIL-AF investigators set out to study the question of whether frail, elderly patients with atrial fibrillation who were doing well with vitamin K antagonists (VKA) should be switched to direct-acting oral anticoagulants (DOAC).

Senior author Geert-Jan Geersing, MD, PhD, from the University Medical Center Utrecht (the Netherlands), told me that frustration led him to design this study. He was frustrated that colleagues assumed that evidence in nonfrail patients can always be translated to frail patients. 

Dr. Geersing offered two reasons why common wisdom may be wrong. First was that the large DOAC versus warfarin trials included few elderly patients with frailty. Second, first author Linda Joosten, MD, made it clear in her presentation that frailty is a lot more than aging. It is a clinical syndrome, which entails a “high burden of comorbidities, dependency on others, and a reduced ability to resist stressors.”
 

The FRAIL-AF trial

The investigators recruited elderly, frail patients with fibrillation who were treated with VKAs and had stable international normalized ratios from outpatient clinics throughout the Netherlands. They screened about 2,600 patients and enrolled nearly 1,400. Most were excluded for not being frail.

Half the group was randomized to switching to a DOAC – drug choice was left to the treating clinician – and the other half remained on VKAs. Patients were 83 years of age on average with a mean CHA2DS2-VASc score of 4. All four classes of DOAC were used in the switching arm.

The primary endpoint was major or clinically relevant nonmajor bleeding, whichever came first, accounting for death as a competing risk. Follow-up was 1 year.
 

The results for switching to DOAC vs. VKA

Dr. Joosten started her presentation with this: “The results turned out to be different than we expected.” The authors designed the trial with the idea that switching to DOACs would be superior in safety to remaining on VKAs.

But the trial was halted after an interim analysis found a rate of major bleeding in the switching arm of 15.3% versus 9.4% in the arm staying on VKA (hazard ratio, 1.69; 95% confidence interval, 1.23-2.32; P = .0012).

The Kaplan-Meier event curves reveal that the excess risk of bleeding occurred after 100 days and increased with time. This argued against an early effect from transitioning the drugs.

An analysis looking at specific DOAC drugs revealed similar hazards for the two most common ones used – apixaban and rivaroxaban.

Thrombotic events were a secondary endpoint and were low in absolute numbers, 2.4% versus 2.0%, for remaining on VKA and switching to DOAC, respectively (HR, 1.26; 95% CI, 0.60-2.61).

The time in therapeutic range in FRAIL-AF was similar to that in the seminal DOAC trials.
 

Comments

Three reasons lead me to choose FRAIL-AF as the most important study from the 2023 ESC congress.

First is the specific lesson about switching drugs. Note that FRAIL-AF did not address the question of starting anticoagulation. The trial results show that if you have a frail older patient who is doing well on VKA, don’t change to a DOAC. That is important to know, but it is not what gives this study its heft.

The second reason centers on the investigators choice to do this trial. Dr. Geersing had a feeling that common wisdom was wrong. He did not try to persuade colleagues with anecdote or plausibility or meta-analyses of observational studies. He set out to answer a question in the correct way – with a randomized trial.

This is the path forward in medicine. I’ve often heard proponents of observational research declare that many topics in medicine cannot be studied with trials. I could hear people arguing that it’s not feasible to study mostly home-bound, elderly frail patients. And the fact that there exist so few trials in this space would support that argument.

But the FRAIL-AF authors showed that it is possible. This is the kind of science that medicine should celebrate. There were no soft endpoints, financial conflicts, or spin. If medical science had science as its incentive, rather than attention, FRAIL-AF easily wins top honors.

The third reason FRAIL-AF is so important is that it teaches us the humility required in translating evidence in our clinics. I like to say evidence is what separates doctors from palm readers. But using this evidence requires thinking hard about how average effects in trial environments apply to our patient.

Yes, of course, there is clear evidence from tens of thousands of patients in the DOAC versus warfarin trials, that, for those patients, on average, DOACs compare favorably with VKA. The average age of patients in these trials was 70-73 years; the average age in FRAIL-AF was 83 years. And that is just age. A substudy of the ENGAGE AF-TIMI 48 trial found that only 360 of more than 20,000 patients in the trial had severe frailty.

FRAIL-AF clearly shows how cautious we should be in applying evidence gathered in younger, healthier patients to older, more vulnerable patients. That lesson extends to nearly every common therapy in medicine today. It also casts great doubt on the soft-thinking idea of using evidence from trials to derive quality metrics. As if the nuance of evidence translation can be captured in an electronic health record.

The skillful use of evidence will be one of the main challenges of the next generation of clinicians. Thanks to advances in medical science, more patients will live long enough to become frail. And the so-called “guideline-directed” therapies may not apply to them.

Dr. Joosten, Dr. Geersing, and the FRAIL-AF team have taught us specific lessons about anticoagulation, but their greatest contribution has been to demonstrate the value of humility in science and the practice of evidence-based medicine.

If you treat patients, no trial at this meeting is more important.

Dr. Mandrola is a clinical electrophysiologist at Baptist Medical Associates, Louisville, Ky. He reported no relevant conflicts of interest.
 

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

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‘Decapitated’ boy saved by surgery team

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Tue, 09/12/2023 - 12:48

 

This transcript has been edited for clarity.
 

F. Perry Wilson, MD, MSCE: I am joined today by Dr. Ohad Einav. He’s a staff surgeon in orthopedics at Hadassah Medical Center in Jerusalem. He’s with me to talk about an absolutely incredible surgical case, something that is terrifying to most non–orthopedic surgeons and I imagine is fairly scary for spine surgeons like him as well. It’s a case of internal decapitation that has generated a lot of news around the world because it happened to a young boy. But what we don’t have is information about how this works from a medical perspective. So, first of all, Dr. Einav, thank you for taking time to speak with me today.

Ohad Einav, MD: Thank you for having me.

Dr. Wilson: Can you tell us about Suleiman Hassan and what happened to him before he came into your care?

Dr. Einav: Hassan is a 12-year-old child who was riding his bicycle on the West Bank, about 40 minutes from here. Unfortunately, he was involved in a motor vehicle accident and he suffered injuries to his abdomen and cervical spine. He was transported to our service by helicopter from the scene of the accident.

Hadassah Medical Center


Dr. Wilson:
 “Injury to the cervical spine” might be something of an understatement. He had what’s called atlanto-occipital dislocation, colloquially often referred to as internal decapitation. Can you tell us what that means? It sounds terrifying.

Dr. Einav: It’s an injury to the ligaments between the occiput and the upper cervical spine, with or without bony fracture. The atlanto-occipital joint is formed by the superior articular facet of the atlas and the occipital condyle, stabilized by an articular capsule between the head and neck, and is supported by various ligaments around it that stabilize the joint and allow joint movements, including flexion, extension, and some rotation in the lower levels.

Dr. Wilson: This joint has several degrees of freedom, which means it needs a lot of support. With this type of injury, where essentially you have severing of the ligaments, is it usually survivable? How dangerous is this?

Dr. Einav: The mortality rate is 50%-60%, depending on the primary impact, the injury, transportation later on, and then the surgery and surgical management.

Dr. Wilson: Tell us a bit about this patient’s status when he came to your medical center. I assume he was in bad shape.

Dr. Einav: Hassan arrived at our medical center with a Glasgow Coma Scale score of 15. He was fully conscious. He was hemodynamically stable except for a bad laceration on his abdomen. He had a Philadelphia collar around his neck. He was transported by chopper because the paramedics suspected that he had a cervical spine injury and decided to bring him to a Level 1 trauma center.

He was monitored and we treated him according to the ATLS [advanced trauma life support] protocol. He didn’t have any gross sensory deficits, but he was a little confused about the whole situation and the accident. Therefore, we could do a general examination but we couldn’t rely on that regarding any sensory deficit that he may or may not have. We decided as a team that it would be better to slow down and control the situation. We decided not to operate on him immediately. We basically stabilized him and made sure that he didn’t have any traumatic internal organ damage. Later on we took him to the OR and performed surgery.

Dr. Wilson: It’s amazing that he had intact motor function, considering the extent of his injury. The spinal cord was spared somewhat during the injury. There must have been a moment when you realized that this kid, who was conscious and could move all four extremities, had a very severe neck injury. Was that due to a CT scan or physical exam? And what was your feeling when you saw that he had atlanto-occipital dislocation?

Dr. Einav: As a surgeon, you have a gut feeling in regard to the general examination of the patient. But I never rely on gut feelings. On the CT, I understood exactly what he had, what we needed to do, and the time frame.

Dr. Wilson: You’ve done these types of surgeries before, right? Obviously, no one has done a lot of them because this isn’t very common. But you knew what to do. Did you have a plan? Where does your experience come into play in a situation like this?

Dr. Einav: I graduated from the spine program of Toronto University, where I did a fellowship in trauma of the spine and complex spine surgery. I had very good teachers, and during my fellowship I treated a few cases in older patients that were similar but not the same. Therefore, I knew exactly what needed to be done.

Dr. Wilson: For those of us who aren’t surgeons, take us into the OR with you. This is obviously an incredibly delicate procedure. You are high up in the spinal cord at the base of the brain. The slightest mistake could have devastating consequences. What are the key elements of this procedure? What can go wrong here? What is the number-one thing you have to look out for when you’re trying to fix an internal decapitation?

Dr. Einav: The key element in surgeries of the cervical spine – trauma and complex spine surgery – is planning. I never go to the OR without knowing what I’m going to do. I have a few plans – plan A, plan B, plan C – in case something fails. So, I definitely know what the next step will be. I always think about the surgery a few hours before, if I have time to prepare.

The second thing that is very important is teamwork. The team needs to be coordinated. Everybody needs to know what their job is. With these types of injuries, it’s not the time for rookies. If you are new, please stand back and let the more experienced people do that job. I’m talking about surgeons, nurses, anesthesiologists – everyone.

Another important thing in planning is choosing the right hardware. For example, in this case we had a problem because most of the hardware is designed for adults, and we had to improvise because there isn’t a lot of hardware on the market for the pediatric population. The adult plates and screws are too big, so we had to improvise.

Dr. Wilson: Tell us more about that. How do you improvise spinal hardware for a 12-year-old?
 

 

 

Hadassah Medical Center


Dr. Einav:
 In this case, I chose to use hardware from one of the companies that works with us.

You can see in this model the area of the injury, and the area that we worked on. To perform the surgery, I had to use some plates and rods from a different company. This company’s (NuVasive) hardware has a small attachment to the skull, which was helpful for affixing the skull to the cervical spine, instead of using a big plate that would sit at the base of the skull and would not be very good for him. Most of the hardware is made for adults and not for kids.

Dr. Wilson: Will that hardware preserve the motor function of his neck? Will he be able to turn his head and extend and flex it?

Dr. Einav: The injury leads to instability and destruction of both articulations between the head and neck. Therefore, those articulations won’t be able to function the same way in the future. There is a decrease of something like 50% of the flexion and extension of Hassan’s cervical spine. Therefore, I decided that in this case there would be no chance of saving Hassan’s motor function unless we performed a fusion between the head and the neck, and therefore I decided that this would be the best procedure with the best survival rate. So, in the future, he will have some diminished flexion, extension, and rotation of his head.

Dr. Wilson: How long did his surgery take?

Dr. Einav: To be honest, I don’t remember. But I can tell you that it took us time. It was very challenging to coordinate with everyone. The most problematic part of the surgery to perform is what we call “flip-over.”

The anesthesiologist intubated the patient when he was supine, and later on, we flipped him prone to operate on the spine. This maneuver can actually lead to injury by itself, and injury at this level is fatal. So, we took our time and got Hassan into the OR. The anesthesiologist did a great job with the GlideScope – inserting the endotracheal tube. Later on, we neuromonitored him. Basically, we connected Hassan’s peripheral nerves to a computer and monitored his motor function. Gently we flipped him over, and after that we saw a little change in his motor function, so we had to modify his position so we could preserve his motor function. We then started the procedure, which took a few hours. I don’t know exactly how many.

Dr. Wilson: That just speaks to how delicate this is for everything from the intubation, where typically you’re manipulating the head, to the repositioning. Clearly this requires a lot of teamwork.

What happened after the operation? How is he doing?

Dr. Einav: After the operation, Hassan had a great recovery. He’s doing well. He doesn’t have any motor or sensory deficits. He’s able to ambulate without any aid. He had no signs of infection, which can happen after a car accident, neither from his abdominal wound nor from the occipital cervical surgery. He feels well. We saw him in the clinic. We removed his collar. We monitored him at the clinic. He looked amazing.

Dr. Wilson: That’s incredible. Are there long-term risks for him that you need to be looking out for?

Dr. Einav: Yes, and that’s the reason that we are monitoring him post surgery. While he was in the hospital, we monitored his motor and sensory functions, as well as his wound healing. Later on, in the clinic, for a few weeks after surgery we monitored for any failure of the hardware and bone graft. We check for healing of the bone graft and bone substitutes we put in to heal those bones.

Dr. Wilson: He will grow, right? He’s only 12, so he still has some years of growth in him. Is he going to need more surgery or any kind of hardware upgrade?

Dr. Einav: I hope not. In my surgeries, I never rely on the hardware for long durations. If I decide to do, for example, fusion, I rely on the hardware for a certain amount of time. And then I plan that the biology will do the work. If I plan for fusion, I put bone grafts in the preferred area for a fusion. Then if the hardware fails, I wouldn’t need to take out the hardware, and there would be no change in the condition of the patient.

Dr. Wilson: What an incredible story. It’s clear that you and your team kept your cool despite a very high-acuity situation with a ton of risk. What a tremendous outcome that this boy is not only alive but fully functional. So, congratulations to you and your team. That was very strong work.

Dr. Einav: Thank you very much. I would like to thank our team. We have to remember that the surgeon is not standing alone in the war. Hassan’s story is a success story of a very big group of people from various backgrounds and religions. They work day and night to help people and save lives. To the paramedics, the physiologists, the traumatologists, the pediatricians, the nurses, the physiotherapists, and obviously the surgeons, a big thank you. His story is our success story.

Dr. Wilson: It’s inspiring to see so many people come together to do what we all are here for, which is to fight against suffering, disease, and death. Thank you for keeping up that fight. And thank you for joining me here.

Dr. Einav: Thank you very much.

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

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This transcript has been edited for clarity.
 

F. Perry Wilson, MD, MSCE: I am joined today by Dr. Ohad Einav. He’s a staff surgeon in orthopedics at Hadassah Medical Center in Jerusalem. He’s with me to talk about an absolutely incredible surgical case, something that is terrifying to most non–orthopedic surgeons and I imagine is fairly scary for spine surgeons like him as well. It’s a case of internal decapitation that has generated a lot of news around the world because it happened to a young boy. But what we don’t have is information about how this works from a medical perspective. So, first of all, Dr. Einav, thank you for taking time to speak with me today.

Ohad Einav, MD: Thank you for having me.

Dr. Wilson: Can you tell us about Suleiman Hassan and what happened to him before he came into your care?

Dr. Einav: Hassan is a 12-year-old child who was riding his bicycle on the West Bank, about 40 minutes from here. Unfortunately, he was involved in a motor vehicle accident and he suffered injuries to his abdomen and cervical spine. He was transported to our service by helicopter from the scene of the accident.

Hadassah Medical Center


Dr. Wilson:
 “Injury to the cervical spine” might be something of an understatement. He had what’s called atlanto-occipital dislocation, colloquially often referred to as internal decapitation. Can you tell us what that means? It sounds terrifying.

Dr. Einav: It’s an injury to the ligaments between the occiput and the upper cervical spine, with or without bony fracture. The atlanto-occipital joint is formed by the superior articular facet of the atlas and the occipital condyle, stabilized by an articular capsule between the head and neck, and is supported by various ligaments around it that stabilize the joint and allow joint movements, including flexion, extension, and some rotation in the lower levels.

Dr. Wilson: This joint has several degrees of freedom, which means it needs a lot of support. With this type of injury, where essentially you have severing of the ligaments, is it usually survivable? How dangerous is this?

Dr. Einav: The mortality rate is 50%-60%, depending on the primary impact, the injury, transportation later on, and then the surgery and surgical management.

Dr. Wilson: Tell us a bit about this patient’s status when he came to your medical center. I assume he was in bad shape.

Dr. Einav: Hassan arrived at our medical center with a Glasgow Coma Scale score of 15. He was fully conscious. He was hemodynamically stable except for a bad laceration on his abdomen. He had a Philadelphia collar around his neck. He was transported by chopper because the paramedics suspected that he had a cervical spine injury and decided to bring him to a Level 1 trauma center.

He was monitored and we treated him according to the ATLS [advanced trauma life support] protocol. He didn’t have any gross sensory deficits, but he was a little confused about the whole situation and the accident. Therefore, we could do a general examination but we couldn’t rely on that regarding any sensory deficit that he may or may not have. We decided as a team that it would be better to slow down and control the situation. We decided not to operate on him immediately. We basically stabilized him and made sure that he didn’t have any traumatic internal organ damage. Later on we took him to the OR and performed surgery.

Dr. Wilson: It’s amazing that he had intact motor function, considering the extent of his injury. The spinal cord was spared somewhat during the injury. There must have been a moment when you realized that this kid, who was conscious and could move all four extremities, had a very severe neck injury. Was that due to a CT scan or physical exam? And what was your feeling when you saw that he had atlanto-occipital dislocation?

Dr. Einav: As a surgeon, you have a gut feeling in regard to the general examination of the patient. But I never rely on gut feelings. On the CT, I understood exactly what he had, what we needed to do, and the time frame.

Dr. Wilson: You’ve done these types of surgeries before, right? Obviously, no one has done a lot of them because this isn’t very common. But you knew what to do. Did you have a plan? Where does your experience come into play in a situation like this?

Dr. Einav: I graduated from the spine program of Toronto University, where I did a fellowship in trauma of the spine and complex spine surgery. I had very good teachers, and during my fellowship I treated a few cases in older patients that were similar but not the same. Therefore, I knew exactly what needed to be done.

Dr. Wilson: For those of us who aren’t surgeons, take us into the OR with you. This is obviously an incredibly delicate procedure. You are high up in the spinal cord at the base of the brain. The slightest mistake could have devastating consequences. What are the key elements of this procedure? What can go wrong here? What is the number-one thing you have to look out for when you’re trying to fix an internal decapitation?

Dr. Einav: The key element in surgeries of the cervical spine – trauma and complex spine surgery – is planning. I never go to the OR without knowing what I’m going to do. I have a few plans – plan A, plan B, plan C – in case something fails. So, I definitely know what the next step will be. I always think about the surgery a few hours before, if I have time to prepare.

The second thing that is very important is teamwork. The team needs to be coordinated. Everybody needs to know what their job is. With these types of injuries, it’s not the time for rookies. If you are new, please stand back and let the more experienced people do that job. I’m talking about surgeons, nurses, anesthesiologists – everyone.

Another important thing in planning is choosing the right hardware. For example, in this case we had a problem because most of the hardware is designed for adults, and we had to improvise because there isn’t a lot of hardware on the market for the pediatric population. The adult plates and screws are too big, so we had to improvise.

Dr. Wilson: Tell us more about that. How do you improvise spinal hardware for a 12-year-old?
 

 

 

Hadassah Medical Center


Dr. Einav:
 In this case, I chose to use hardware from one of the companies that works with us.

You can see in this model the area of the injury, and the area that we worked on. To perform the surgery, I had to use some plates and rods from a different company. This company’s (NuVasive) hardware has a small attachment to the skull, which was helpful for affixing the skull to the cervical spine, instead of using a big plate that would sit at the base of the skull and would not be very good for him. Most of the hardware is made for adults and not for kids.

Dr. Wilson: Will that hardware preserve the motor function of his neck? Will he be able to turn his head and extend and flex it?

Dr. Einav: The injury leads to instability and destruction of both articulations between the head and neck. Therefore, those articulations won’t be able to function the same way in the future. There is a decrease of something like 50% of the flexion and extension of Hassan’s cervical spine. Therefore, I decided that in this case there would be no chance of saving Hassan’s motor function unless we performed a fusion between the head and the neck, and therefore I decided that this would be the best procedure with the best survival rate. So, in the future, he will have some diminished flexion, extension, and rotation of his head.

Dr. Wilson: How long did his surgery take?

Dr. Einav: To be honest, I don’t remember. But I can tell you that it took us time. It was very challenging to coordinate with everyone. The most problematic part of the surgery to perform is what we call “flip-over.”

The anesthesiologist intubated the patient when he was supine, and later on, we flipped him prone to operate on the spine. This maneuver can actually lead to injury by itself, and injury at this level is fatal. So, we took our time and got Hassan into the OR. The anesthesiologist did a great job with the GlideScope – inserting the endotracheal tube. Later on, we neuromonitored him. Basically, we connected Hassan’s peripheral nerves to a computer and monitored his motor function. Gently we flipped him over, and after that we saw a little change in his motor function, so we had to modify his position so we could preserve his motor function. We then started the procedure, which took a few hours. I don’t know exactly how many.

Dr. Wilson: That just speaks to how delicate this is for everything from the intubation, where typically you’re manipulating the head, to the repositioning. Clearly this requires a lot of teamwork.

What happened after the operation? How is he doing?

Dr. Einav: After the operation, Hassan had a great recovery. He’s doing well. He doesn’t have any motor or sensory deficits. He’s able to ambulate without any aid. He had no signs of infection, which can happen after a car accident, neither from his abdominal wound nor from the occipital cervical surgery. He feels well. We saw him in the clinic. We removed his collar. We monitored him at the clinic. He looked amazing.

Dr. Wilson: That’s incredible. Are there long-term risks for him that you need to be looking out for?

Dr. Einav: Yes, and that’s the reason that we are monitoring him post surgery. While he was in the hospital, we monitored his motor and sensory functions, as well as his wound healing. Later on, in the clinic, for a few weeks after surgery we monitored for any failure of the hardware and bone graft. We check for healing of the bone graft and bone substitutes we put in to heal those bones.

Dr. Wilson: He will grow, right? He’s only 12, so he still has some years of growth in him. Is he going to need more surgery or any kind of hardware upgrade?

Dr. Einav: I hope not. In my surgeries, I never rely on the hardware for long durations. If I decide to do, for example, fusion, I rely on the hardware for a certain amount of time. And then I plan that the biology will do the work. If I plan for fusion, I put bone grafts in the preferred area for a fusion. Then if the hardware fails, I wouldn’t need to take out the hardware, and there would be no change in the condition of the patient.

Dr. Wilson: What an incredible story. It’s clear that you and your team kept your cool despite a very high-acuity situation with a ton of risk. What a tremendous outcome that this boy is not only alive but fully functional. So, congratulations to you and your team. That was very strong work.

Dr. Einav: Thank you very much. I would like to thank our team. We have to remember that the surgeon is not standing alone in the war. Hassan’s story is a success story of a very big group of people from various backgrounds and religions. They work day and night to help people and save lives. To the paramedics, the physiologists, the traumatologists, the pediatricians, the nurses, the physiotherapists, and obviously the surgeons, a big thank you. His story is our success story.

Dr. Wilson: It’s inspiring to see so many people come together to do what we all are here for, which is to fight against suffering, disease, and death. Thank you for keeping up that fight. And thank you for joining me here.

Dr. Einav: Thank you very much.

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

 

This transcript has been edited for clarity.
 

F. Perry Wilson, MD, MSCE: I am joined today by Dr. Ohad Einav. He’s a staff surgeon in orthopedics at Hadassah Medical Center in Jerusalem. He’s with me to talk about an absolutely incredible surgical case, something that is terrifying to most non–orthopedic surgeons and I imagine is fairly scary for spine surgeons like him as well. It’s a case of internal decapitation that has generated a lot of news around the world because it happened to a young boy. But what we don’t have is information about how this works from a medical perspective. So, first of all, Dr. Einav, thank you for taking time to speak with me today.

Ohad Einav, MD: Thank you for having me.

Dr. Wilson: Can you tell us about Suleiman Hassan and what happened to him before he came into your care?

Dr. Einav: Hassan is a 12-year-old child who was riding his bicycle on the West Bank, about 40 minutes from here. Unfortunately, he was involved in a motor vehicle accident and he suffered injuries to his abdomen and cervical spine. He was transported to our service by helicopter from the scene of the accident.

Hadassah Medical Center


Dr. Wilson:
 “Injury to the cervical spine” might be something of an understatement. He had what’s called atlanto-occipital dislocation, colloquially often referred to as internal decapitation. Can you tell us what that means? It sounds terrifying.

Dr. Einav: It’s an injury to the ligaments between the occiput and the upper cervical spine, with or without bony fracture. The atlanto-occipital joint is formed by the superior articular facet of the atlas and the occipital condyle, stabilized by an articular capsule between the head and neck, and is supported by various ligaments around it that stabilize the joint and allow joint movements, including flexion, extension, and some rotation in the lower levels.

Dr. Wilson: This joint has several degrees of freedom, which means it needs a lot of support. With this type of injury, where essentially you have severing of the ligaments, is it usually survivable? How dangerous is this?

Dr. Einav: The mortality rate is 50%-60%, depending on the primary impact, the injury, transportation later on, and then the surgery and surgical management.

Dr. Wilson: Tell us a bit about this patient’s status when he came to your medical center. I assume he was in bad shape.

Dr. Einav: Hassan arrived at our medical center with a Glasgow Coma Scale score of 15. He was fully conscious. He was hemodynamically stable except for a bad laceration on his abdomen. He had a Philadelphia collar around his neck. He was transported by chopper because the paramedics suspected that he had a cervical spine injury and decided to bring him to a Level 1 trauma center.

He was monitored and we treated him according to the ATLS [advanced trauma life support] protocol. He didn’t have any gross sensory deficits, but he was a little confused about the whole situation and the accident. Therefore, we could do a general examination but we couldn’t rely on that regarding any sensory deficit that he may or may not have. We decided as a team that it would be better to slow down and control the situation. We decided not to operate on him immediately. We basically stabilized him and made sure that he didn’t have any traumatic internal organ damage. Later on we took him to the OR and performed surgery.

Dr. Wilson: It’s amazing that he had intact motor function, considering the extent of his injury. The spinal cord was spared somewhat during the injury. There must have been a moment when you realized that this kid, who was conscious and could move all four extremities, had a very severe neck injury. Was that due to a CT scan or physical exam? And what was your feeling when you saw that he had atlanto-occipital dislocation?

Dr. Einav: As a surgeon, you have a gut feeling in regard to the general examination of the patient. But I never rely on gut feelings. On the CT, I understood exactly what he had, what we needed to do, and the time frame.

Dr. Wilson: You’ve done these types of surgeries before, right? Obviously, no one has done a lot of them because this isn’t very common. But you knew what to do. Did you have a plan? Where does your experience come into play in a situation like this?

Dr. Einav: I graduated from the spine program of Toronto University, where I did a fellowship in trauma of the spine and complex spine surgery. I had very good teachers, and during my fellowship I treated a few cases in older patients that were similar but not the same. Therefore, I knew exactly what needed to be done.

Dr. Wilson: For those of us who aren’t surgeons, take us into the OR with you. This is obviously an incredibly delicate procedure. You are high up in the spinal cord at the base of the brain. The slightest mistake could have devastating consequences. What are the key elements of this procedure? What can go wrong here? What is the number-one thing you have to look out for when you’re trying to fix an internal decapitation?

Dr. Einav: The key element in surgeries of the cervical spine – trauma and complex spine surgery – is planning. I never go to the OR without knowing what I’m going to do. I have a few plans – plan A, plan B, plan C – in case something fails. So, I definitely know what the next step will be. I always think about the surgery a few hours before, if I have time to prepare.

The second thing that is very important is teamwork. The team needs to be coordinated. Everybody needs to know what their job is. With these types of injuries, it’s not the time for rookies. If you are new, please stand back and let the more experienced people do that job. I’m talking about surgeons, nurses, anesthesiologists – everyone.

Another important thing in planning is choosing the right hardware. For example, in this case we had a problem because most of the hardware is designed for adults, and we had to improvise because there isn’t a lot of hardware on the market for the pediatric population. The adult plates and screws are too big, so we had to improvise.

Dr. Wilson: Tell us more about that. How do you improvise spinal hardware for a 12-year-old?
 

 

 

Hadassah Medical Center


Dr. Einav:
 In this case, I chose to use hardware from one of the companies that works with us.

You can see in this model the area of the injury, and the area that we worked on. To perform the surgery, I had to use some plates and rods from a different company. This company’s (NuVasive) hardware has a small attachment to the skull, which was helpful for affixing the skull to the cervical spine, instead of using a big plate that would sit at the base of the skull and would not be very good for him. Most of the hardware is made for adults and not for kids.

Dr. Wilson: Will that hardware preserve the motor function of his neck? Will he be able to turn his head and extend and flex it?

Dr. Einav: The injury leads to instability and destruction of both articulations between the head and neck. Therefore, those articulations won’t be able to function the same way in the future. There is a decrease of something like 50% of the flexion and extension of Hassan’s cervical spine. Therefore, I decided that in this case there would be no chance of saving Hassan’s motor function unless we performed a fusion between the head and the neck, and therefore I decided that this would be the best procedure with the best survival rate. So, in the future, he will have some diminished flexion, extension, and rotation of his head.

Dr. Wilson: How long did his surgery take?

Dr. Einav: To be honest, I don’t remember. But I can tell you that it took us time. It was very challenging to coordinate with everyone. The most problematic part of the surgery to perform is what we call “flip-over.”

The anesthesiologist intubated the patient when he was supine, and later on, we flipped him prone to operate on the spine. This maneuver can actually lead to injury by itself, and injury at this level is fatal. So, we took our time and got Hassan into the OR. The anesthesiologist did a great job with the GlideScope – inserting the endotracheal tube. Later on, we neuromonitored him. Basically, we connected Hassan’s peripheral nerves to a computer and monitored his motor function. Gently we flipped him over, and after that we saw a little change in his motor function, so we had to modify his position so we could preserve his motor function. We then started the procedure, which took a few hours. I don’t know exactly how many.

Dr. Wilson: That just speaks to how delicate this is for everything from the intubation, where typically you’re manipulating the head, to the repositioning. Clearly this requires a lot of teamwork.

What happened after the operation? How is he doing?

Dr. Einav: After the operation, Hassan had a great recovery. He’s doing well. He doesn’t have any motor or sensory deficits. He’s able to ambulate without any aid. He had no signs of infection, which can happen after a car accident, neither from his abdominal wound nor from the occipital cervical surgery. He feels well. We saw him in the clinic. We removed his collar. We monitored him at the clinic. He looked amazing.

Dr. Wilson: That’s incredible. Are there long-term risks for him that you need to be looking out for?

Dr. Einav: Yes, and that’s the reason that we are monitoring him post surgery. While he was in the hospital, we monitored his motor and sensory functions, as well as his wound healing. Later on, in the clinic, for a few weeks after surgery we monitored for any failure of the hardware and bone graft. We check for healing of the bone graft and bone substitutes we put in to heal those bones.

Dr. Wilson: He will grow, right? He’s only 12, so he still has some years of growth in him. Is he going to need more surgery or any kind of hardware upgrade?

Dr. Einav: I hope not. In my surgeries, I never rely on the hardware for long durations. If I decide to do, for example, fusion, I rely on the hardware for a certain amount of time. And then I plan that the biology will do the work. If I plan for fusion, I put bone grafts in the preferred area for a fusion. Then if the hardware fails, I wouldn’t need to take out the hardware, and there would be no change in the condition of the patient.

Dr. Wilson: What an incredible story. It’s clear that you and your team kept your cool despite a very high-acuity situation with a ton of risk. What a tremendous outcome that this boy is not only alive but fully functional. So, congratulations to you and your team. That was very strong work.

Dr. Einav: Thank you very much. I would like to thank our team. We have to remember that the surgeon is not standing alone in the war. Hassan’s story is a success story of a very big group of people from various backgrounds and religions. They work day and night to help people and save lives. To the paramedics, the physiologists, the traumatologists, the pediatricians, the nurses, the physiotherapists, and obviously the surgeons, a big thank you. His story is our success story.

Dr. Wilson: It’s inspiring to see so many people come together to do what we all are here for, which is to fight against suffering, disease, and death. Thank you for keeping up that fight. And thank you for joining me here.

Dr. Einav: Thank you very much.

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

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Treatments for Hidradenitis Suppurativa Comorbidities Help With Pain Management

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Treatments for Hidradenitis Suppurativa Comorbidities Help With Pain Management

Hidradenitis suppurativa (HS) has an unpredictable disease course and poses substantial therapeutic challenges. It carries an increased risk for adverse cardiovascular outcomes and all-cause mortality. It also is associated with comorbidities including mood disorders, tobacco smoking, obesity, diabetes mellitus, sleep disorders, sexual dysfunction, and autoimmune diseases, which can complicate its management and considerably affect patients’ quality of life (QOL).1 Hidradenitis suppurativa also disproportionately affects minority groups and has far-reaching inequities; for example, the condition has a notable economic impact on patients, including higher unemployment and disability rates, lower-paying jobs, less paid time off, and other indirect costs.2,3 Race can impact how pain itself is treated. In one study (N = 217), Black patients with extremity fractures presenting to anemergency department were significantly less likely to receive analgesia compared to White patients despite reporting similar pain (57% vs 74%, respectively; P = .01).4 In another study, Hispanic patients were 7-times less likely to be treated with opioids compared to non-Hispanic patients with long-bone fractures.5 Herein, we highlight pain management disparities in HS patients.

Treating HS Comorbidities Helps Improve Pain

Pain is reported by almost all HS patients and is the symptom most associated with QOL impairment.6,7 Pain in HS is multifactorial, with other symptoms and comorbidities affecting its severity. Treatment of acute flares often is painful and procedural, including intralesional steroid injections or incision and drainage.8 Algorithms for addressing pain through the treatment of comorbidities also have been developed.6 Although there are few studies on the medications that treat related comorbidities in HS, there is evidence of their benefits in similar diseases; for example, treating depression in patients with irritable bowel disease (IBD) improved pain perception, cognitive function, and sexual dysfunction.9

Depression exacerbates pain, and higher levels of depression have been observed in severe HS.10,11 Additionally, more than 80% of individuals with HS report tobacco smoking.1 Nicotine not only increases pain sensitivity and decreases pain tolerance but also worsens neuropathic, nociceptive, and psychosocial pain, as well as mood disorders and sleep disturbances.12 Given the higher prevalence of depression and smoking in HS patients and the impact on pain, addressing these comorbidities is crucial. Additionally, poor sleep amplifies pain sensitivity and affects neurologic pain modulation.13 Chronic pain also is associated with obesity and sleep dysfunction.14

Treatments Targeting Pain and Comorbidities

Treatments that target comorbidities and other symptoms of HS also may improve pain. Bupropion is a well-studied antidepressant and first-line option to aid in smoking cessation. It provides acute and chronic pain relief associated with IBD and may perform similarly in patients with HS.15-18 Bupropion also demonstrated dose-dependent weight reduction in obese and overweight individuals.19,20 Additionally, varenicline is a first-line option to aid in smoking cessation and can be combined with bupropion to increase long-term efficacy.21,22

Other antidepressants may alleviate HS pain. The selective norepinephrine reuptake inhibitors duloxetine and venlafaxine are recommended for chronic pain in HS.6 Selective serotonin reuptake inhibitors such as citalopram, escitalopram, and paroxetine are inexpensive and widely available antidepressants. Citalopram is as efficacious as duloxetine for chronic pain with fewer side effects.23 Paroxetine has been shown to improve pain and pruritus, QOL, and depression in patients with IBD.24 Benefits such as improved weight and sexual dysfunction also have been reported.25

Metformin is well studied in Black patients, and greater glycemic response supports its efficacy for diabetes as well as HS, which disproportionately affects individuals with skin of color.26 Metformin also targets other comorbidities of HS, such as improving insulin resistance, polycystic ovary syndrome, acne vulgaris, weight loss, hyperlipidemia, cardiovascular risk, and neuropsychologic conditions.27 Growing evidence supports the use of metformin as a new agent in chronic pain management, specifically for patients with HS.28,29

Final Thoughts

Hidradenitis suppurativa is a complex medical condition seen disproportionately in minority groups. Understanding common comorbidities as well as the biases associated with pain management will allow providers to treat HS patients more effectively. Dermatologists who see many HS patients should become more familiar with treating these associated comorbidities to provide patient care that is more holistic and effective.

References
  1. Garg A, Malviya N, Strunk A, et al. Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations. J Am Acad Dermatol. 2022;86:1092-1101. doi:10.1016/j.jaad.2021.01.059
  2. Tzellos T, Yang H, Mu F, et al. Impact of hidradenitis suppurativa on work loss, indirect costs and income. Br J Dermatol. 2019;181:147-154. doi:10.1111/bjd.17101
  3. Udechukwu NS, Fleischer AB. Higher risk of care for hidradenitis suppurativa in African American and non-Hispanic patients in the United States. J Natl Med Assoc. 2017;109:44-48. doi:10.1016/j.jnma.2016.09.002
  4. Todd KH, Deaton C, D’Adamo AP, et al. Ethnicity and analgesic practice. Ann Emerg Med. 2000;35:11-16. doi:10.1016/s0196-0644(00)70099-0
  5. Todd KH, Samaroo N, Hoffman JR. Ethnicity as a risk factor for inadequate emergency department analgesia. JAMA. 1993;269:1537-1539.
  6. Savage KT, Singh V, Patel ZS, et al. Pain management in hidradenitis suppurativa and a proposed treatment algorithm. J Am Acad Dermatol. 2021;85:187-199. doi:10.1016/j.jaad.2020.09.039
  7. Matusiak Ł, Szcze˛ch J, Kaaz K, et al. Clinical characteristics of pruritus and pain in patients with hidradenitis suppurativa. Acta Derm Venereol. 2018;98:191-194. doi:10.2340/00015555-2815
  8. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part I: diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019;81:76-90. doi:10.1016/j.jaad.2019.02.067
  9. Walker EA, Gelfand MD, Gelfand AN, et al. The relationship of current psychiatric disorder to functional disability and distress in patients with inflammatory bowel disease. Gen Hosp Psychiatry. 1996;18:220-229. doi:10.1016/0163-8343(96)00036-9
  10. Phan K, Huo YR, Smith SD. Hidradenitis suppurativa and psychiatric comorbidities, suicides and substance abuse: systematic review and meta-analysis. Ann Transl Med. 2020;8:821. doi:10.21037/atm-20-1028
  11. Woo AK. Depression and anxiety in pain. Rev Pain. 2010;4:8-12. doi:10.1177/204946371000400103
  12. Iida H, Yamaguchi S, Goyagi T, et al. Consensus statement on smoking cessation in patients with pain. J Anesth. 2022;36:671-687. doi:10.1007/s00540-022-03097-w
  13. Krause AJ, Prather AA, Wager TD, et al. The pain of sleep loss: a brain characterization in humans. J Neurosci. 2019;39:2291-2300. doi:10.1523/JNEUROSCI.2408-18.2018
  14. Mundal I, Gråwe RW, Bjørngaard JH, et al. Prevalence and long-term predictors of persistent chronic widespread pain in the general population in an 11-year prospective study: the HUNT study. BMC Musculoskelet Disord. 2014;15:213. doi:10.1186/1471-2474-15-213
  15. Aubin H-J. Tolerability and safety of sustained-release bupropion in the management of smoking cessation. Drugs. 2002;(62 suppl 2):45-52. doi:10.2165/00003495-200262002-00005
  16. Shah TH, Moradimehr A. Bupropion for the treatment of neuropathic pain. Am J Hosp Palliat Care. 2010;27:333-336. doi:10.1177/1049909110361229
  17. Baune BT, Renger L. Pharmacological and non-pharmacological interventions to improve cognitive dysfunction and functional ability in clinical depression—a systematic review. Psychiatry Res. 2014;219:25-50. doi:10.1016/j.psychres.2014.05.013
  18. Walker PW, Cole JO, Gardner EA, et al. Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion. J Clin Psychiatry. 1993;54:459-465.
  19. Sherman MM, Ungureanu S, Rey JA. Naltrexone/bupropion ER (contrave): newly approved treatment option for chronic weight management in obese adults. P T. 2016;41:164-172.
  20. Anderson JW, Greenway FL, Fujioka K, et al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obes Res. 2002;10:633-641. doi:10.1038/oby.2002.86
  21. Kalkhoran S, Benowitz NL, Rigotti NA. Prevention and treatment of tobacco use: JACC health promotion series. J Am Coll Cardiol. 2018;72:1030-1045. doi:10.1016/j.jacc.2018.06.036
  22. Singh D, Saadabadi A. Varenicline. StatPearls Publishing; 2023.
  23. Mazza M, Mazza O, Pazzaglia C, et al. Escitalopram 20 mg versus duloxetine 60 mg for the treatment of chronic low back pain. Expert Opin Pharmacother. 2010;11:1049-1052. doi:10.1517/14656561003730413
  24. Docherty MJ, Jones RCW, Wallace MS. Managing pain in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011;7:592-601.
  25. Shrestha P, Fariba KA, Abdijadid S. Paroxetine. StatPearls Publishing; 2022.
  26. Williams LK, Padhukasahasram B, Ahmedani BK, et al. Differing effects of metformin on glycemic control by race-ethnicity. J Clin Endocrinol Metab. 2014;99:3160-3168. doi:10.1210/jc.2014-1539
  27. Sharma S, Mathur DK, Paliwal V, et al. Efficacy of metformin in the treatment of acne in women with polycystic ovarian syndrome: a newer approach to acne therapy. J Clin Aesthet Dermatol. 2019;12:34-38.
  28. Scheinfeld N. Hidradenitis suppurativa: a practical review of possible medical treatments based on over 350 hidradenitis patients. Dermatol Online J. 2013;19:1. doi:10.5070/D35VW402NF
  29. Baeza-Flores GDC, Guzmán-Priego CG, Parra-Flores LI, et al. Metformin: a prospective alternative for the treatment of chronic pain. Front Pharmacol. 2020;11:558474. doi:10.3389/fphar.2020.558474
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From the Division of Dermatology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois. Austin C. Casillas and Victor A. Barragan also are from the Department of Dermatopathology. 

The authors report no conflict of interest.

Correspondence: Eden Lake, MD ([email protected]).

Revised February 12, 2024.

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From the Division of Dermatology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois. Austin C. Casillas and Victor A. Barragan also are from the Department of Dermatopathology. 

The authors report no conflict of interest.

Correspondence: Eden Lake, MD ([email protected]).

Revised February 12, 2024.

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From the Division of Dermatology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois. Austin C. Casillas and Victor A. Barragan also are from the Department of Dermatopathology. 

The authors report no conflict of interest.

Correspondence: Eden Lake, MD ([email protected]).

Revised February 12, 2024.

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Hidradenitis suppurativa (HS) has an unpredictable disease course and poses substantial therapeutic challenges. It carries an increased risk for adverse cardiovascular outcomes and all-cause mortality. It also is associated with comorbidities including mood disorders, tobacco smoking, obesity, diabetes mellitus, sleep disorders, sexual dysfunction, and autoimmune diseases, which can complicate its management and considerably affect patients’ quality of life (QOL).1 Hidradenitis suppurativa also disproportionately affects minority groups and has far-reaching inequities; for example, the condition has a notable economic impact on patients, including higher unemployment and disability rates, lower-paying jobs, less paid time off, and other indirect costs.2,3 Race can impact how pain itself is treated. In one study (N = 217), Black patients with extremity fractures presenting to anemergency department were significantly less likely to receive analgesia compared to White patients despite reporting similar pain (57% vs 74%, respectively; P = .01).4 In another study, Hispanic patients were 7-times less likely to be treated with opioids compared to non-Hispanic patients with long-bone fractures.5 Herein, we highlight pain management disparities in HS patients.

Treating HS Comorbidities Helps Improve Pain

Pain is reported by almost all HS patients and is the symptom most associated with QOL impairment.6,7 Pain in HS is multifactorial, with other symptoms and comorbidities affecting its severity. Treatment of acute flares often is painful and procedural, including intralesional steroid injections or incision and drainage.8 Algorithms for addressing pain through the treatment of comorbidities also have been developed.6 Although there are few studies on the medications that treat related comorbidities in HS, there is evidence of their benefits in similar diseases; for example, treating depression in patients with irritable bowel disease (IBD) improved pain perception, cognitive function, and sexual dysfunction.9

Depression exacerbates pain, and higher levels of depression have been observed in severe HS.10,11 Additionally, more than 80% of individuals with HS report tobacco smoking.1 Nicotine not only increases pain sensitivity and decreases pain tolerance but also worsens neuropathic, nociceptive, and psychosocial pain, as well as mood disorders and sleep disturbances.12 Given the higher prevalence of depression and smoking in HS patients and the impact on pain, addressing these comorbidities is crucial. Additionally, poor sleep amplifies pain sensitivity and affects neurologic pain modulation.13 Chronic pain also is associated with obesity and sleep dysfunction.14

Treatments Targeting Pain and Comorbidities

Treatments that target comorbidities and other symptoms of HS also may improve pain. Bupropion is a well-studied antidepressant and first-line option to aid in smoking cessation. It provides acute and chronic pain relief associated with IBD and may perform similarly in patients with HS.15-18 Bupropion also demonstrated dose-dependent weight reduction in obese and overweight individuals.19,20 Additionally, varenicline is a first-line option to aid in smoking cessation and can be combined with bupropion to increase long-term efficacy.21,22

Other antidepressants may alleviate HS pain. The selective norepinephrine reuptake inhibitors duloxetine and venlafaxine are recommended for chronic pain in HS.6 Selective serotonin reuptake inhibitors such as citalopram, escitalopram, and paroxetine are inexpensive and widely available antidepressants. Citalopram is as efficacious as duloxetine for chronic pain with fewer side effects.23 Paroxetine has been shown to improve pain and pruritus, QOL, and depression in patients with IBD.24 Benefits such as improved weight and sexual dysfunction also have been reported.25

Metformin is well studied in Black patients, and greater glycemic response supports its efficacy for diabetes as well as HS, which disproportionately affects individuals with skin of color.26 Metformin also targets other comorbidities of HS, such as improving insulin resistance, polycystic ovary syndrome, acne vulgaris, weight loss, hyperlipidemia, cardiovascular risk, and neuropsychologic conditions.27 Growing evidence supports the use of metformin as a new agent in chronic pain management, specifically for patients with HS.28,29

Final Thoughts

Hidradenitis suppurativa is a complex medical condition seen disproportionately in minority groups. Understanding common comorbidities as well as the biases associated with pain management will allow providers to treat HS patients more effectively. Dermatologists who see many HS patients should become more familiar with treating these associated comorbidities to provide patient care that is more holistic and effective.

Hidradenitis suppurativa (HS) has an unpredictable disease course and poses substantial therapeutic challenges. It carries an increased risk for adverse cardiovascular outcomes and all-cause mortality. It also is associated with comorbidities including mood disorders, tobacco smoking, obesity, diabetes mellitus, sleep disorders, sexual dysfunction, and autoimmune diseases, which can complicate its management and considerably affect patients’ quality of life (QOL).1 Hidradenitis suppurativa also disproportionately affects minority groups and has far-reaching inequities; for example, the condition has a notable economic impact on patients, including higher unemployment and disability rates, lower-paying jobs, less paid time off, and other indirect costs.2,3 Race can impact how pain itself is treated. In one study (N = 217), Black patients with extremity fractures presenting to anemergency department were significantly less likely to receive analgesia compared to White patients despite reporting similar pain (57% vs 74%, respectively; P = .01).4 In another study, Hispanic patients were 7-times less likely to be treated with opioids compared to non-Hispanic patients with long-bone fractures.5 Herein, we highlight pain management disparities in HS patients.

Treating HS Comorbidities Helps Improve Pain

Pain is reported by almost all HS patients and is the symptom most associated with QOL impairment.6,7 Pain in HS is multifactorial, with other symptoms and comorbidities affecting its severity. Treatment of acute flares often is painful and procedural, including intralesional steroid injections or incision and drainage.8 Algorithms for addressing pain through the treatment of comorbidities also have been developed.6 Although there are few studies on the medications that treat related comorbidities in HS, there is evidence of their benefits in similar diseases; for example, treating depression in patients with irritable bowel disease (IBD) improved pain perception, cognitive function, and sexual dysfunction.9

Depression exacerbates pain, and higher levels of depression have been observed in severe HS.10,11 Additionally, more than 80% of individuals with HS report tobacco smoking.1 Nicotine not only increases pain sensitivity and decreases pain tolerance but also worsens neuropathic, nociceptive, and psychosocial pain, as well as mood disorders and sleep disturbances.12 Given the higher prevalence of depression and smoking in HS patients and the impact on pain, addressing these comorbidities is crucial. Additionally, poor sleep amplifies pain sensitivity and affects neurologic pain modulation.13 Chronic pain also is associated with obesity and sleep dysfunction.14

Treatments Targeting Pain and Comorbidities

Treatments that target comorbidities and other symptoms of HS also may improve pain. Bupropion is a well-studied antidepressant and first-line option to aid in smoking cessation. It provides acute and chronic pain relief associated with IBD and may perform similarly in patients with HS.15-18 Bupropion also demonstrated dose-dependent weight reduction in obese and overweight individuals.19,20 Additionally, varenicline is a first-line option to aid in smoking cessation and can be combined with bupropion to increase long-term efficacy.21,22

Other antidepressants may alleviate HS pain. The selective norepinephrine reuptake inhibitors duloxetine and venlafaxine are recommended for chronic pain in HS.6 Selective serotonin reuptake inhibitors such as citalopram, escitalopram, and paroxetine are inexpensive and widely available antidepressants. Citalopram is as efficacious as duloxetine for chronic pain with fewer side effects.23 Paroxetine has been shown to improve pain and pruritus, QOL, and depression in patients with IBD.24 Benefits such as improved weight and sexual dysfunction also have been reported.25

Metformin is well studied in Black patients, and greater glycemic response supports its efficacy for diabetes as well as HS, which disproportionately affects individuals with skin of color.26 Metformin also targets other comorbidities of HS, such as improving insulin resistance, polycystic ovary syndrome, acne vulgaris, weight loss, hyperlipidemia, cardiovascular risk, and neuropsychologic conditions.27 Growing evidence supports the use of metformin as a new agent in chronic pain management, specifically for patients with HS.28,29

Final Thoughts

Hidradenitis suppurativa is a complex medical condition seen disproportionately in minority groups. Understanding common comorbidities as well as the biases associated with pain management will allow providers to treat HS patients more effectively. Dermatologists who see many HS patients should become more familiar with treating these associated comorbidities to provide patient care that is more holistic and effective.

References
  1. Garg A, Malviya N, Strunk A, et al. Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations. J Am Acad Dermatol. 2022;86:1092-1101. doi:10.1016/j.jaad.2021.01.059
  2. Tzellos T, Yang H, Mu F, et al. Impact of hidradenitis suppurativa on work loss, indirect costs and income. Br J Dermatol. 2019;181:147-154. doi:10.1111/bjd.17101
  3. Udechukwu NS, Fleischer AB. Higher risk of care for hidradenitis suppurativa in African American and non-Hispanic patients in the United States. J Natl Med Assoc. 2017;109:44-48. doi:10.1016/j.jnma.2016.09.002
  4. Todd KH, Deaton C, D’Adamo AP, et al. Ethnicity and analgesic practice. Ann Emerg Med. 2000;35:11-16. doi:10.1016/s0196-0644(00)70099-0
  5. Todd KH, Samaroo N, Hoffman JR. Ethnicity as a risk factor for inadequate emergency department analgesia. JAMA. 1993;269:1537-1539.
  6. Savage KT, Singh V, Patel ZS, et al. Pain management in hidradenitis suppurativa and a proposed treatment algorithm. J Am Acad Dermatol. 2021;85:187-199. doi:10.1016/j.jaad.2020.09.039
  7. Matusiak Ł, Szcze˛ch J, Kaaz K, et al. Clinical characteristics of pruritus and pain in patients with hidradenitis suppurativa. Acta Derm Venereol. 2018;98:191-194. doi:10.2340/00015555-2815
  8. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part I: diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019;81:76-90. doi:10.1016/j.jaad.2019.02.067
  9. Walker EA, Gelfand MD, Gelfand AN, et al. The relationship of current psychiatric disorder to functional disability and distress in patients with inflammatory bowel disease. Gen Hosp Psychiatry. 1996;18:220-229. doi:10.1016/0163-8343(96)00036-9
  10. Phan K, Huo YR, Smith SD. Hidradenitis suppurativa and psychiatric comorbidities, suicides and substance abuse: systematic review and meta-analysis. Ann Transl Med. 2020;8:821. doi:10.21037/atm-20-1028
  11. Woo AK. Depression and anxiety in pain. Rev Pain. 2010;4:8-12. doi:10.1177/204946371000400103
  12. Iida H, Yamaguchi S, Goyagi T, et al. Consensus statement on smoking cessation in patients with pain. J Anesth. 2022;36:671-687. doi:10.1007/s00540-022-03097-w
  13. Krause AJ, Prather AA, Wager TD, et al. The pain of sleep loss: a brain characterization in humans. J Neurosci. 2019;39:2291-2300. doi:10.1523/JNEUROSCI.2408-18.2018
  14. Mundal I, Gråwe RW, Bjørngaard JH, et al. Prevalence and long-term predictors of persistent chronic widespread pain in the general population in an 11-year prospective study: the HUNT study. BMC Musculoskelet Disord. 2014;15:213. doi:10.1186/1471-2474-15-213
  15. Aubin H-J. Tolerability and safety of sustained-release bupropion in the management of smoking cessation. Drugs. 2002;(62 suppl 2):45-52. doi:10.2165/00003495-200262002-00005
  16. Shah TH, Moradimehr A. Bupropion for the treatment of neuropathic pain. Am J Hosp Palliat Care. 2010;27:333-336. doi:10.1177/1049909110361229
  17. Baune BT, Renger L. Pharmacological and non-pharmacological interventions to improve cognitive dysfunction and functional ability in clinical depression—a systematic review. Psychiatry Res. 2014;219:25-50. doi:10.1016/j.psychres.2014.05.013
  18. Walker PW, Cole JO, Gardner EA, et al. Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion. J Clin Psychiatry. 1993;54:459-465.
  19. Sherman MM, Ungureanu S, Rey JA. Naltrexone/bupropion ER (contrave): newly approved treatment option for chronic weight management in obese adults. P T. 2016;41:164-172.
  20. Anderson JW, Greenway FL, Fujioka K, et al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obes Res. 2002;10:633-641. doi:10.1038/oby.2002.86
  21. Kalkhoran S, Benowitz NL, Rigotti NA. Prevention and treatment of tobacco use: JACC health promotion series. J Am Coll Cardiol. 2018;72:1030-1045. doi:10.1016/j.jacc.2018.06.036
  22. Singh D, Saadabadi A. Varenicline. StatPearls Publishing; 2023.
  23. Mazza M, Mazza O, Pazzaglia C, et al. Escitalopram 20 mg versus duloxetine 60 mg for the treatment of chronic low back pain. Expert Opin Pharmacother. 2010;11:1049-1052. doi:10.1517/14656561003730413
  24. Docherty MJ, Jones RCW, Wallace MS. Managing pain in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011;7:592-601.
  25. Shrestha P, Fariba KA, Abdijadid S. Paroxetine. StatPearls Publishing; 2022.
  26. Williams LK, Padhukasahasram B, Ahmedani BK, et al. Differing effects of metformin on glycemic control by race-ethnicity. J Clin Endocrinol Metab. 2014;99:3160-3168. doi:10.1210/jc.2014-1539
  27. Sharma S, Mathur DK, Paliwal V, et al. Efficacy of metformin in the treatment of acne in women with polycystic ovarian syndrome: a newer approach to acne therapy. J Clin Aesthet Dermatol. 2019;12:34-38.
  28. Scheinfeld N. Hidradenitis suppurativa: a practical review of possible medical treatments based on over 350 hidradenitis patients. Dermatol Online J. 2013;19:1. doi:10.5070/D35VW402NF
  29. Baeza-Flores GDC, Guzmán-Priego CG, Parra-Flores LI, et al. Metformin: a prospective alternative for the treatment of chronic pain. Front Pharmacol. 2020;11:558474. doi:10.3389/fphar.2020.558474
References
  1. Garg A, Malviya N, Strunk A, et al. Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations. J Am Acad Dermatol. 2022;86:1092-1101. doi:10.1016/j.jaad.2021.01.059
  2. Tzellos T, Yang H, Mu F, et al. Impact of hidradenitis suppurativa on work loss, indirect costs and income. Br J Dermatol. 2019;181:147-154. doi:10.1111/bjd.17101
  3. Udechukwu NS, Fleischer AB. Higher risk of care for hidradenitis suppurativa in African American and non-Hispanic patients in the United States. J Natl Med Assoc. 2017;109:44-48. doi:10.1016/j.jnma.2016.09.002
  4. Todd KH, Deaton C, D’Adamo AP, et al. Ethnicity and analgesic practice. Ann Emerg Med. 2000;35:11-16. doi:10.1016/s0196-0644(00)70099-0
  5. Todd KH, Samaroo N, Hoffman JR. Ethnicity as a risk factor for inadequate emergency department analgesia. JAMA. 1993;269:1537-1539.
  6. Savage KT, Singh V, Patel ZS, et al. Pain management in hidradenitis suppurativa and a proposed treatment algorithm. J Am Acad Dermatol. 2021;85:187-199. doi:10.1016/j.jaad.2020.09.039
  7. Matusiak Ł, Szcze˛ch J, Kaaz K, et al. Clinical characteristics of pruritus and pain in patients with hidradenitis suppurativa. Acta Derm Venereol. 2018;98:191-194. doi:10.2340/00015555-2815
  8. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part I: diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019;81:76-90. doi:10.1016/j.jaad.2019.02.067
  9. Walker EA, Gelfand MD, Gelfand AN, et al. The relationship of current psychiatric disorder to functional disability and distress in patients with inflammatory bowel disease. Gen Hosp Psychiatry. 1996;18:220-229. doi:10.1016/0163-8343(96)00036-9
  10. Phan K, Huo YR, Smith SD. Hidradenitis suppurativa and psychiatric comorbidities, suicides and substance abuse: systematic review and meta-analysis. Ann Transl Med. 2020;8:821. doi:10.21037/atm-20-1028
  11. Woo AK. Depression and anxiety in pain. Rev Pain. 2010;4:8-12. doi:10.1177/204946371000400103
  12. Iida H, Yamaguchi S, Goyagi T, et al. Consensus statement on smoking cessation in patients with pain. J Anesth. 2022;36:671-687. doi:10.1007/s00540-022-03097-w
  13. Krause AJ, Prather AA, Wager TD, et al. The pain of sleep loss: a brain characterization in humans. J Neurosci. 2019;39:2291-2300. doi:10.1523/JNEUROSCI.2408-18.2018
  14. Mundal I, Gråwe RW, Bjørngaard JH, et al. Prevalence and long-term predictors of persistent chronic widespread pain in the general population in an 11-year prospective study: the HUNT study. BMC Musculoskelet Disord. 2014;15:213. doi:10.1186/1471-2474-15-213
  15. Aubin H-J. Tolerability and safety of sustained-release bupropion in the management of smoking cessation. Drugs. 2002;(62 suppl 2):45-52. doi:10.2165/00003495-200262002-00005
  16. Shah TH, Moradimehr A. Bupropion for the treatment of neuropathic pain. Am J Hosp Palliat Care. 2010;27:333-336. doi:10.1177/1049909110361229
  17. Baune BT, Renger L. Pharmacological and non-pharmacological interventions to improve cognitive dysfunction and functional ability in clinical depression—a systematic review. Psychiatry Res. 2014;219:25-50. doi:10.1016/j.psychres.2014.05.013
  18. Walker PW, Cole JO, Gardner EA, et al. Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion. J Clin Psychiatry. 1993;54:459-465.
  19. Sherman MM, Ungureanu S, Rey JA. Naltrexone/bupropion ER (contrave): newly approved treatment option for chronic weight management in obese adults. P T. 2016;41:164-172.
  20. Anderson JW, Greenway FL, Fujioka K, et al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obes Res. 2002;10:633-641. doi:10.1038/oby.2002.86
  21. Kalkhoran S, Benowitz NL, Rigotti NA. Prevention and treatment of tobacco use: JACC health promotion series. J Am Coll Cardiol. 2018;72:1030-1045. doi:10.1016/j.jacc.2018.06.036
  22. Singh D, Saadabadi A. Varenicline. StatPearls Publishing; 2023.
  23. Mazza M, Mazza O, Pazzaglia C, et al. Escitalopram 20 mg versus duloxetine 60 mg for the treatment of chronic low back pain. Expert Opin Pharmacother. 2010;11:1049-1052. doi:10.1517/14656561003730413
  24. Docherty MJ, Jones RCW, Wallace MS. Managing pain in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011;7:592-601.
  25. Shrestha P, Fariba KA, Abdijadid S. Paroxetine. StatPearls Publishing; 2022.
  26. Williams LK, Padhukasahasram B, Ahmedani BK, et al. Differing effects of metformin on glycemic control by race-ethnicity. J Clin Endocrinol Metab. 2014;99:3160-3168. doi:10.1210/jc.2014-1539
  27. Sharma S, Mathur DK, Paliwal V, et al. Efficacy of metformin in the treatment of acne in women with polycystic ovarian syndrome: a newer approach to acne therapy. J Clin Aesthet Dermatol. 2019;12:34-38.
  28. Scheinfeld N. Hidradenitis suppurativa: a practical review of possible medical treatments based on over 350 hidradenitis patients. Dermatol Online J. 2013;19:1. doi:10.5070/D35VW402NF
  29. Baeza-Flores GDC, Guzmán-Priego CG, Parra-Flores LI, et al. Metformin: a prospective alternative for the treatment of chronic pain. Front Pharmacol. 2020;11:558474. doi:10.3389/fphar.2020.558474
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Mammography breast density reporting: What it means for clinicians

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Changed
Fri, 09/01/2023 - 09:51

 

This transcript has been edited for clarity.

Today, I’m going to talk about the 2023 Food and Drug Administration regulation that requires breast density to be reported on all mammogram results nationwide, and for that report to go to both clinicians and patients. Previously this was the rule in some states, but not in others. This is important because 40%-50% of women have dense breasts. I’m going to discuss what that means for you, and for our patients.

First I’ll review what breast density is, and how it is categorized and reported, and then why it’s important and what to do with the results.

Breast density describes the appearance of the breast on mammography. Appearance varies on the basis of breast tissue composition, with fibroglandular tissue being more dense than fatty tissue. Breast density is important because it relates to both the risk for cancer and the ability of mammography to detect cancer.

Breast density is defined and classified according to the American College of Radiology’s BI-RADS four-category scale. Categories 1 and 2 refer to breast tissue that is not dense, accounting for about 50% of the population. Categories 3 and 4 describe heterogeneously dense and extremely dense breast tissue, which occur in approximately 40% and 50% of women, respectively. When speaking about dense breast tissue readings on mammography, we are referring to categories 3 and 4.

Women with dense breast tissue have an increased risk of developing breast cancer and are less likely to have early breast cancer detected on mammography.

Let’s go over the details by category:

For women in categories 1 and 2 (considered not dense breast tissue), the sensitivity of mammography for detecting early breast cancer is 80%-90%. In categories 3 and 4, the sensitivity of mammography drops to 60%-70%.

Compared with women with average breast density, the risk of developing breast cancer is 20% higher in women with BI-RADS category 3 breasts, and more than twice as high (relative risk, 2.1) in those with BI-RADS category 4 breasts. Thus, the risk of developing breast cancer is higher, but the sensitivity of the test is lower.



The clinical question is, what should we do about this? For women who have a normal mammogram with dense breasts, should follow-up testing be done, and if so, what test? The main follow-up testing options are either ultrasound or MRI, usually ultrasound. Additional testing will detect additional cancers that were not picked up on the initial mammogram and will also lead to additional biopsies for false-positive tests from the additional testing.

An American College of Gynecology and Obstetrics practice advisory nicely summarizes the evidence and clarifies that this decision is made in the context of a lack of published evidence demonstrating improved outcomes, specifically no reduction in breast cancer mortality, with supplemental testing. The official ACOG stance is that they “do not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

This is an area where it is important to understand the data. We are all going to be getting test results back that indicate level of breast density, and those test results will also be sent to our patients, so we are going to be asked about this by interested patients. Should this be something that we talk to patients about, utilizing shared decision-making to decide about whether follow-up testing is necessary in women with dense breasts? That is something each clinician will need to decide, and knowing the data is a critically important step in that decision.

Neil Skolnik, MD, is a professor, department of family medicine, at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director, department of family medicine, Abington (Pennsylvania) Jefferson Health.

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

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This transcript has been edited for clarity.

Today, I’m going to talk about the 2023 Food and Drug Administration regulation that requires breast density to be reported on all mammogram results nationwide, and for that report to go to both clinicians and patients. Previously this was the rule in some states, but not in others. This is important because 40%-50% of women have dense breasts. I’m going to discuss what that means for you, and for our patients.

First I’ll review what breast density is, and how it is categorized and reported, and then why it’s important and what to do with the results.

Breast density describes the appearance of the breast on mammography. Appearance varies on the basis of breast tissue composition, with fibroglandular tissue being more dense than fatty tissue. Breast density is important because it relates to both the risk for cancer and the ability of mammography to detect cancer.

Breast density is defined and classified according to the American College of Radiology’s BI-RADS four-category scale. Categories 1 and 2 refer to breast tissue that is not dense, accounting for about 50% of the population. Categories 3 and 4 describe heterogeneously dense and extremely dense breast tissue, which occur in approximately 40% and 50% of women, respectively. When speaking about dense breast tissue readings on mammography, we are referring to categories 3 and 4.

Women with dense breast tissue have an increased risk of developing breast cancer and are less likely to have early breast cancer detected on mammography.

Let’s go over the details by category:

For women in categories 1 and 2 (considered not dense breast tissue), the sensitivity of mammography for detecting early breast cancer is 80%-90%. In categories 3 and 4, the sensitivity of mammography drops to 60%-70%.

Compared with women with average breast density, the risk of developing breast cancer is 20% higher in women with BI-RADS category 3 breasts, and more than twice as high (relative risk, 2.1) in those with BI-RADS category 4 breasts. Thus, the risk of developing breast cancer is higher, but the sensitivity of the test is lower.



The clinical question is, what should we do about this? For women who have a normal mammogram with dense breasts, should follow-up testing be done, and if so, what test? The main follow-up testing options are either ultrasound or MRI, usually ultrasound. Additional testing will detect additional cancers that were not picked up on the initial mammogram and will also lead to additional biopsies for false-positive tests from the additional testing.

An American College of Gynecology and Obstetrics practice advisory nicely summarizes the evidence and clarifies that this decision is made in the context of a lack of published evidence demonstrating improved outcomes, specifically no reduction in breast cancer mortality, with supplemental testing. The official ACOG stance is that they “do not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

This is an area where it is important to understand the data. We are all going to be getting test results back that indicate level of breast density, and those test results will also be sent to our patients, so we are going to be asked about this by interested patients. Should this be something that we talk to patients about, utilizing shared decision-making to decide about whether follow-up testing is necessary in women with dense breasts? That is something each clinician will need to decide, and knowing the data is a critically important step in that decision.

Neil Skolnik, MD, is a professor, department of family medicine, at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director, department of family medicine, Abington (Pennsylvania) Jefferson Health.

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

 

This transcript has been edited for clarity.

Today, I’m going to talk about the 2023 Food and Drug Administration regulation that requires breast density to be reported on all mammogram results nationwide, and for that report to go to both clinicians and patients. Previously this was the rule in some states, but not in others. This is important because 40%-50% of women have dense breasts. I’m going to discuss what that means for you, and for our patients.

First I’ll review what breast density is, and how it is categorized and reported, and then why it’s important and what to do with the results.

Breast density describes the appearance of the breast on mammography. Appearance varies on the basis of breast tissue composition, with fibroglandular tissue being more dense than fatty tissue. Breast density is important because it relates to both the risk for cancer and the ability of mammography to detect cancer.

Breast density is defined and classified according to the American College of Radiology’s BI-RADS four-category scale. Categories 1 and 2 refer to breast tissue that is not dense, accounting for about 50% of the population. Categories 3 and 4 describe heterogeneously dense and extremely dense breast tissue, which occur in approximately 40% and 50% of women, respectively. When speaking about dense breast tissue readings on mammography, we are referring to categories 3 and 4.

Women with dense breast tissue have an increased risk of developing breast cancer and are less likely to have early breast cancer detected on mammography.

Let’s go over the details by category:

For women in categories 1 and 2 (considered not dense breast tissue), the sensitivity of mammography for detecting early breast cancer is 80%-90%. In categories 3 and 4, the sensitivity of mammography drops to 60%-70%.

Compared with women with average breast density, the risk of developing breast cancer is 20% higher in women with BI-RADS category 3 breasts, and more than twice as high (relative risk, 2.1) in those with BI-RADS category 4 breasts. Thus, the risk of developing breast cancer is higher, but the sensitivity of the test is lower.



The clinical question is, what should we do about this? For women who have a normal mammogram with dense breasts, should follow-up testing be done, and if so, what test? The main follow-up testing options are either ultrasound or MRI, usually ultrasound. Additional testing will detect additional cancers that were not picked up on the initial mammogram and will also lead to additional biopsies for false-positive tests from the additional testing.

An American College of Gynecology and Obstetrics practice advisory nicely summarizes the evidence and clarifies that this decision is made in the context of a lack of published evidence demonstrating improved outcomes, specifically no reduction in breast cancer mortality, with supplemental testing. The official ACOG stance is that they “do not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

This is an area where it is important to understand the data. We are all going to be getting test results back that indicate level of breast density, and those test results will also be sent to our patients, so we are going to be asked about this by interested patients. Should this be something that we talk to patients about, utilizing shared decision-making to decide about whether follow-up testing is necessary in women with dense breasts? That is something each clinician will need to decide, and knowing the data is a critically important step in that decision.

Neil Skolnik, MD, is a professor, department of family medicine, at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director, department of family medicine, Abington (Pennsylvania) Jefferson Health.

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

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A toxic and fractured political system can breed angst and PTSD

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Display Headline
A toxic and fractured political system can breed angst and PTSD

As psychiatrists know, many of our severely traumatized adult patients were victims of abuse during childhood. We routinely ask every new patient about physical, emotional, or sexual abuse when they were growing up because of the well-established, serious neurobiological and mental repercussions.1,2

Perhaps one of the worst experiences for a child is to witness bitterly adversarial parents (their vital role models) who argue viciously, despise each other, and hurl insults (and even punches) at each other. Such a chronically and emotionally traumatic upbringing can haunt kids well into adulthood, disrupting their hypothalamic-pituitary-adrenal axis and triggering anxiety, depression, and even psychosis due to epigenetic changes that ultimately lead to abnormal brain development.3

It often feels that the governance of our country, or the national “political family,” is seriously fractured like a hopelessly dysfunctional family. Could that be negatively impacting the mental health of the citizenry? Having 2 antagonistic political parties expressing visceral hatred and undisguised contempt for each other 24/7 (thanks to the enabling era of cable TV, the internet, and social media) has transformed each party’s fanatic followers from fellow citizens to ideological combatants. In this poisonous societal zeitgeist of bidirectional acrimony and mutual detestation, the opposing parties and their “intellectual militias” label each other as “extremists” or “radicals.” They become completely blind to any redeeming social value in the ideas or principles of their political opponents. They spend enormous time and energy on undermining each other instead of attending to the myriad vital issues involved in the governance of a massive and complex country.

Winston Churchill said, “Democracy is the worst form of government, except for all the others that have been tried.”4 The current toxic cloud of intense “hyperpartisanship” is emblematic of the dark Machiavellian side of democracy. But those who lament the current distorted version of democracy should contemplate living in a dictatorship or totalitarian regime, where a despot would execute any dissenter or invade and destroy an adjacent country at a whim.

Churchill made that statement in 1947. The internet, social media, and smartphones were science fiction back then. Those technological advances have added fuel to the political process and significantly stoked the flames of hyperpartisanship. It’s now democracy on steroids, where freedom of expression goes to extremes, highlighting the warts and pitfalls of the democratic system. Political rivals can now communicate their ferocious disagreements to millions of their disciples instantaneously, triggering immediate rebuttals and counterattacks by their adversaries. This “virtual guerilla warfare” is mentally and emotionally exhausting to all involved, especially to the subset of neutral bystanders who are unaffiliated with either political party, which, due to the “religification” of politics, have become like secular religions.5 Chronic, unremitting, inescapable stress is a sure pathway for anxiety, depression, posttraumatic stress disorder, and even brain atrophy.

Optimists may point out that the United States has weathered and emerged stronger from many serious traumas, including the Civil War (with its lethal divisiveness), World War I, the deadly 1918 influenza pandemic, the Great Depression, Pearl Harbor, World War II, the Cold War, the Vietnam War, the Watergate political scandal, the 9/11 terrorist attacks, the banking collapse and recession, and most recently the COVID-19 pandemic, which brought society to a standstill and induced so much anxiety and uncertainty.

On the other hand, pessimists would insist those sequential crises left indelible scars that cumulatively altered the mindset of political rivals, predisposing them to extreme views of each other. Alienation inevitably leads to fanaticism. It’s perplexing but fascinating how the fierce bidirectional missives of weaponized ideas can be as virulent and destructive as a traditional physical war. Perhaps in this era, the pen is mightier than the sword after all.

Continue to: From a psychiatric perspective...

 

 

From a psychiatric perspective, the intransigent groupthink of political partisanship eerily resembles folie en masse, a psychiatric syndrome for which there is no established treatment. It has become a serious threat to our modern democracy. So I decided to ask the “know-it-all” artificial intelligence ChatGPT, whom I previously had “invited” to write a “guest editorial” about myths surrounding psychiatry,6 to answer 3 burning questions:

1. Is there toxic hyperpartisanship in the USA today? (Box 1)

Box 1

Is there toxic hyperpartisanship in the USA today? (generated by ChatGPT)

Yes, there is toxic hyperpartisanship in the United States today. Political polarization has been on the rise for several decades, and in recent years, it has become increasingly toxic and divisive. This toxic hyperpartisanship has contributed to a breakdown in civil discourse and a lack of cooperation and compromise in government.

The toxic hyperpartisanship is evident in many aspects of American society, including politics, media, and social media. Political leaders often engage in divisive rhetoric and focus on winning at all costs, rather than working towards solutions that benefit the country as a whole. Media outlets often present news in a partisan manner, further fueling political polarization. Social media platforms have also played a role in exacerbating toxic hyperpartisanship by allowing the spread of misinformation and creating echo chambers where people are only exposed to like-minded viewpoints.

The consequences of toxic hyperpartisanship are significant, as it can hinder progress on important issues and erode trust in institutions and government. It also makes it difficult for people to engage in productive dialogue and find common ground, leading to a lack of cooperation and compromise.

It is important for individuals to be aware of the impact of toxic hyperpartisanship and work towards finding ways to bridge the political divide and engage in constructive dialogue.

2. How can severe hyperpartisanship be corrected? (Supplemental Box 1)

Supplemental Box 1

How can severe hyperpartisanship be corrected? (generated by ChatGPT)

Severe hyperpartisanship, characterized by intense and entrenched divisions between political parties, can be a challenging issue to address, but there are several steps that can be taken to work towards correcting it. Here are some potential approaches:

1. Promote civil discourse: Encourage respectful and constructive conversations between individuals with differing political views. This can be achieved through education programs, media campaigns, and initiatives to foster open dialogue.

2. Electoral reforms: Consider implementing electoral reforms that can reduce the influence of extreme partisanship. For example, ranked-choice voting or nonpartisan primaries may encourage candidates to appeal to a broader base of voters rather than just their party’s base.

3. Campaign finance reform: Limit the influence of money in politics, as it can exacerbate hyperpartisanship by allowing wealthy donors to have undue influence over candidates and parties.

4. Independent redistricting: Ensure that electoral district boundaries are drawn in a fair and nonpartisan manner. Gerrymandering, the manipulation of district lines to favor one party, can contribute to hyperpartisanship by creating “safe” districts where extreme candidates are more likely to be elected.

5. Promote media literacy: Encourage media literacy education to help citizens critically evaluate information sources and avoid echo chambers. A well-informed electorate is less susceptible to extreme partisanship.

6. Encourage bipartisan collaboration: Highlight and support instances of successful bipartisan collaboration. Elected officials who work across the aisle can serve as positive examples and encourage others to follow suit.

7. Address economic inequality: Tackling economic disparities can alleviate some of the underlying factors that contribute to polarization. When people feel economically secure, they may be more willing to seek common ground.

8. Civics education: Improve civics education in schools to foster a deeper understanding of democratic values, the political process, and the importance of civic engagement.

9. Leadership example: Encourage political leaders to model cooperation and compromise rather than relying on divisive rhetoric. Voters often take cues from their leaders’ behavior.

10. Promote third parties: Support and encourage the emergence of viable thirdparty candidates. A more diverse political landscape can provide alternatives to extreme partisanship.

11. Focus on common ground: Identify and prioritize issues where there is potential for bipartisan consensus and progress. Building success on these issues can create momentum for further cooperation.

12. Encourage grassroots activism: Support grassroots movements that seek to bridge divides and foster understanding between individuals and communities with different political perspectives.

It’s essential to recognize that addressing severe hyperpartisanship is a complex and long-term process that requires collective effort from citizens, political leaders, educators, and institutions. It won’t be achieved overnight, but through sustained and committed actions, progress can be made toward a more collaborative and less divisive political climate.

3. What can cause the collapse of a democracy? (Supplemental Box 2).

Supplemental Box 2

What can cause the collapse of a democracy? (generated by ChatGPT)

The collapse of a democracy can be a complex and multifaceted process, influenced by various factors and circumstances. Some of the common causes that can lead to the erosion or breakdown of a democratic system include:

1. Authoritarianism and power concentration: When leaders or institutions become increasingly authoritarian, centralizing power and weakening checks and balances, it can undermine democratic principles.

2. Corruption and lack of accountability: Rampant corruption among political leaders and institutions can erode public trust in the democratic system, leading to disillusionment and disengagement.

3. Economic instability: Prolonged economic crises or severe inequality can lead to social unrest, increasing the appeal of populist or extremist movements that may challenge democratic norms.

4. Weakening of rule of law: If the rule of law is weakened, and there is a lack of respect for judicial independence and constitutional principles, democratic institutions can become vulnerable to manipulation.

5. Erosion of civil liberties: Suppression of freedom of speech, media, assembly, and association can limit citizens’ ability to express their opinions and participate in the democratic process.

6. Polarization and divisive politics: Extreme political polarization and a breakdown of civil discourse can hinder cooperation and compromise essential for a functioning democracy.

7. External interference: Foreign intervention, propaganda, or cyberattacks can influence electoral processes and undermine democratic institutions.

8. Rise of populism and nationalism: Populist movements that challenge democratic norms, demonize minorities, or advocate for a strongman leadership can pose a threat to democracy.

9. Demographic and social shifts: Demographic changes and social tensions can exacerbate political divisions and weaken the fabric of democratic societies.

10. Lack of civic education and participation: A lack of civic education and low voter turnout can lead to reduced civic engagement and undermine the democratic process.

It is crucial to understand that no democracy is immune to these challenges, and the strength of a democratic system depends on the vigilance and engagement of its citizens, the integrity of its institutions, and the commitment to upholding democratic values. Safeguarding and strengthening democracy requires ongoing efforts to address these issues and protect the principles that underpin democratic governance.

Judge for yourself, but I believe the ChatGPT responses were spot-on.

References

1. Lippard ETC, Nemeroff CB. The devastating clinical consequences of child abuse and neglect: increased disease vulnerability and poor treatment response in mood disorders. Am J Psychiatry. 2023;180(8):548-564.

2. Nemeroff CB. Paradise lost: the neurobiological and clinical consequences of child abuse and neglect. Neuron. 2016;89(5):892-909.

3. Zhang ZZ, Moeckel C, Mustafa M, et al. The association of epigenetic age acceleration and depressive and anxiety symptom severity among children recently exposed to substantiated maltreatment. J Psychiatr Res. 2023;165:7-13.

4. International Churchill Society. The worst form of government. Accessed August 8, 2023. https://winstonchurchill.org/resources/quotes/the-worst-form-of-government/

5. Nasrallah HA. From ideology to articles of faith: the ‘religification’ of political beliefs. Current Psychiatry. 2021;20(7):4-5,19.

6. Nasrallah HA. A ‘guest editorial’ … generated by ChatGPT? Current Psychiatry. 2023;22(4):22:6-7.

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As psychiatrists know, many of our severely traumatized adult patients were victims of abuse during childhood. We routinely ask every new patient about physical, emotional, or sexual abuse when they were growing up because of the well-established, serious neurobiological and mental repercussions.1,2

Perhaps one of the worst experiences for a child is to witness bitterly adversarial parents (their vital role models) who argue viciously, despise each other, and hurl insults (and even punches) at each other. Such a chronically and emotionally traumatic upbringing can haunt kids well into adulthood, disrupting their hypothalamic-pituitary-adrenal axis and triggering anxiety, depression, and even psychosis due to epigenetic changes that ultimately lead to abnormal brain development.3

It often feels that the governance of our country, or the national “political family,” is seriously fractured like a hopelessly dysfunctional family. Could that be negatively impacting the mental health of the citizenry? Having 2 antagonistic political parties expressing visceral hatred and undisguised contempt for each other 24/7 (thanks to the enabling era of cable TV, the internet, and social media) has transformed each party’s fanatic followers from fellow citizens to ideological combatants. In this poisonous societal zeitgeist of bidirectional acrimony and mutual detestation, the opposing parties and their “intellectual militias” label each other as “extremists” or “radicals.” They become completely blind to any redeeming social value in the ideas or principles of their political opponents. They spend enormous time and energy on undermining each other instead of attending to the myriad vital issues involved in the governance of a massive and complex country.

Winston Churchill said, “Democracy is the worst form of government, except for all the others that have been tried.”4 The current toxic cloud of intense “hyperpartisanship” is emblematic of the dark Machiavellian side of democracy. But those who lament the current distorted version of democracy should contemplate living in a dictatorship or totalitarian regime, where a despot would execute any dissenter or invade and destroy an adjacent country at a whim.

Churchill made that statement in 1947. The internet, social media, and smartphones were science fiction back then. Those technological advances have added fuel to the political process and significantly stoked the flames of hyperpartisanship. It’s now democracy on steroids, where freedom of expression goes to extremes, highlighting the warts and pitfalls of the democratic system. Political rivals can now communicate their ferocious disagreements to millions of their disciples instantaneously, triggering immediate rebuttals and counterattacks by their adversaries. This “virtual guerilla warfare” is mentally and emotionally exhausting to all involved, especially to the subset of neutral bystanders who are unaffiliated with either political party, which, due to the “religification” of politics, have become like secular religions.5 Chronic, unremitting, inescapable stress is a sure pathway for anxiety, depression, posttraumatic stress disorder, and even brain atrophy.

Optimists may point out that the United States has weathered and emerged stronger from many serious traumas, including the Civil War (with its lethal divisiveness), World War I, the deadly 1918 influenza pandemic, the Great Depression, Pearl Harbor, World War II, the Cold War, the Vietnam War, the Watergate political scandal, the 9/11 terrorist attacks, the banking collapse and recession, and most recently the COVID-19 pandemic, which brought society to a standstill and induced so much anxiety and uncertainty.

On the other hand, pessimists would insist those sequential crises left indelible scars that cumulatively altered the mindset of political rivals, predisposing them to extreme views of each other. Alienation inevitably leads to fanaticism. It’s perplexing but fascinating how the fierce bidirectional missives of weaponized ideas can be as virulent and destructive as a traditional physical war. Perhaps in this era, the pen is mightier than the sword after all.

Continue to: From a psychiatric perspective...

 

 

From a psychiatric perspective, the intransigent groupthink of political partisanship eerily resembles folie en masse, a psychiatric syndrome for which there is no established treatment. It has become a serious threat to our modern democracy. So I decided to ask the “know-it-all” artificial intelligence ChatGPT, whom I previously had “invited” to write a “guest editorial” about myths surrounding psychiatry,6 to answer 3 burning questions:

1. Is there toxic hyperpartisanship in the USA today? (Box 1)

Box 1

Is there toxic hyperpartisanship in the USA today? (generated by ChatGPT)

Yes, there is toxic hyperpartisanship in the United States today. Political polarization has been on the rise for several decades, and in recent years, it has become increasingly toxic and divisive. This toxic hyperpartisanship has contributed to a breakdown in civil discourse and a lack of cooperation and compromise in government.

The toxic hyperpartisanship is evident in many aspects of American society, including politics, media, and social media. Political leaders often engage in divisive rhetoric and focus on winning at all costs, rather than working towards solutions that benefit the country as a whole. Media outlets often present news in a partisan manner, further fueling political polarization. Social media platforms have also played a role in exacerbating toxic hyperpartisanship by allowing the spread of misinformation and creating echo chambers where people are only exposed to like-minded viewpoints.

The consequences of toxic hyperpartisanship are significant, as it can hinder progress on important issues and erode trust in institutions and government. It also makes it difficult for people to engage in productive dialogue and find common ground, leading to a lack of cooperation and compromise.

It is important for individuals to be aware of the impact of toxic hyperpartisanship and work towards finding ways to bridge the political divide and engage in constructive dialogue.

2. How can severe hyperpartisanship be corrected? (Supplemental Box 1)

Supplemental Box 1

How can severe hyperpartisanship be corrected? (generated by ChatGPT)

Severe hyperpartisanship, characterized by intense and entrenched divisions between political parties, can be a challenging issue to address, but there are several steps that can be taken to work towards correcting it. Here are some potential approaches:

1. Promote civil discourse: Encourage respectful and constructive conversations between individuals with differing political views. This can be achieved through education programs, media campaigns, and initiatives to foster open dialogue.

2. Electoral reforms: Consider implementing electoral reforms that can reduce the influence of extreme partisanship. For example, ranked-choice voting or nonpartisan primaries may encourage candidates to appeal to a broader base of voters rather than just their party’s base.

3. Campaign finance reform: Limit the influence of money in politics, as it can exacerbate hyperpartisanship by allowing wealthy donors to have undue influence over candidates and parties.

4. Independent redistricting: Ensure that electoral district boundaries are drawn in a fair and nonpartisan manner. Gerrymandering, the manipulation of district lines to favor one party, can contribute to hyperpartisanship by creating “safe” districts where extreme candidates are more likely to be elected.

5. Promote media literacy: Encourage media literacy education to help citizens critically evaluate information sources and avoid echo chambers. A well-informed electorate is less susceptible to extreme partisanship.

6. Encourage bipartisan collaboration: Highlight and support instances of successful bipartisan collaboration. Elected officials who work across the aisle can serve as positive examples and encourage others to follow suit.

7. Address economic inequality: Tackling economic disparities can alleviate some of the underlying factors that contribute to polarization. When people feel economically secure, they may be more willing to seek common ground.

8. Civics education: Improve civics education in schools to foster a deeper understanding of democratic values, the political process, and the importance of civic engagement.

9. Leadership example: Encourage political leaders to model cooperation and compromise rather than relying on divisive rhetoric. Voters often take cues from their leaders’ behavior.

10. Promote third parties: Support and encourage the emergence of viable thirdparty candidates. A more diverse political landscape can provide alternatives to extreme partisanship.

11. Focus on common ground: Identify and prioritize issues where there is potential for bipartisan consensus and progress. Building success on these issues can create momentum for further cooperation.

12. Encourage grassroots activism: Support grassroots movements that seek to bridge divides and foster understanding between individuals and communities with different political perspectives.

It’s essential to recognize that addressing severe hyperpartisanship is a complex and long-term process that requires collective effort from citizens, political leaders, educators, and institutions. It won’t be achieved overnight, but through sustained and committed actions, progress can be made toward a more collaborative and less divisive political climate.

3. What can cause the collapse of a democracy? (Supplemental Box 2).

Supplemental Box 2

What can cause the collapse of a democracy? (generated by ChatGPT)

The collapse of a democracy can be a complex and multifaceted process, influenced by various factors and circumstances. Some of the common causes that can lead to the erosion or breakdown of a democratic system include:

1. Authoritarianism and power concentration: When leaders or institutions become increasingly authoritarian, centralizing power and weakening checks and balances, it can undermine democratic principles.

2. Corruption and lack of accountability: Rampant corruption among political leaders and institutions can erode public trust in the democratic system, leading to disillusionment and disengagement.

3. Economic instability: Prolonged economic crises or severe inequality can lead to social unrest, increasing the appeal of populist or extremist movements that may challenge democratic norms.

4. Weakening of rule of law: If the rule of law is weakened, and there is a lack of respect for judicial independence and constitutional principles, democratic institutions can become vulnerable to manipulation.

5. Erosion of civil liberties: Suppression of freedom of speech, media, assembly, and association can limit citizens’ ability to express their opinions and participate in the democratic process.

6. Polarization and divisive politics: Extreme political polarization and a breakdown of civil discourse can hinder cooperation and compromise essential for a functioning democracy.

7. External interference: Foreign intervention, propaganda, or cyberattacks can influence electoral processes and undermine democratic institutions.

8. Rise of populism and nationalism: Populist movements that challenge democratic norms, demonize minorities, or advocate for a strongman leadership can pose a threat to democracy.

9. Demographic and social shifts: Demographic changes and social tensions can exacerbate political divisions and weaken the fabric of democratic societies.

10. Lack of civic education and participation: A lack of civic education and low voter turnout can lead to reduced civic engagement and undermine the democratic process.

It is crucial to understand that no democracy is immune to these challenges, and the strength of a democratic system depends on the vigilance and engagement of its citizens, the integrity of its institutions, and the commitment to upholding democratic values. Safeguarding and strengthening democracy requires ongoing efforts to address these issues and protect the principles that underpin democratic governance.

Judge for yourself, but I believe the ChatGPT responses were spot-on.

As psychiatrists know, many of our severely traumatized adult patients were victims of abuse during childhood. We routinely ask every new patient about physical, emotional, or sexual abuse when they were growing up because of the well-established, serious neurobiological and mental repercussions.1,2

Perhaps one of the worst experiences for a child is to witness bitterly adversarial parents (their vital role models) who argue viciously, despise each other, and hurl insults (and even punches) at each other. Such a chronically and emotionally traumatic upbringing can haunt kids well into adulthood, disrupting their hypothalamic-pituitary-adrenal axis and triggering anxiety, depression, and even psychosis due to epigenetic changes that ultimately lead to abnormal brain development.3

It often feels that the governance of our country, or the national “political family,” is seriously fractured like a hopelessly dysfunctional family. Could that be negatively impacting the mental health of the citizenry? Having 2 antagonistic political parties expressing visceral hatred and undisguised contempt for each other 24/7 (thanks to the enabling era of cable TV, the internet, and social media) has transformed each party’s fanatic followers from fellow citizens to ideological combatants. In this poisonous societal zeitgeist of bidirectional acrimony and mutual detestation, the opposing parties and their “intellectual militias” label each other as “extremists” or “radicals.” They become completely blind to any redeeming social value in the ideas or principles of their political opponents. They spend enormous time and energy on undermining each other instead of attending to the myriad vital issues involved in the governance of a massive and complex country.

Winston Churchill said, “Democracy is the worst form of government, except for all the others that have been tried.”4 The current toxic cloud of intense “hyperpartisanship” is emblematic of the dark Machiavellian side of democracy. But those who lament the current distorted version of democracy should contemplate living in a dictatorship or totalitarian regime, where a despot would execute any dissenter or invade and destroy an adjacent country at a whim.

Churchill made that statement in 1947. The internet, social media, and smartphones were science fiction back then. Those technological advances have added fuel to the political process and significantly stoked the flames of hyperpartisanship. It’s now democracy on steroids, where freedom of expression goes to extremes, highlighting the warts and pitfalls of the democratic system. Political rivals can now communicate their ferocious disagreements to millions of their disciples instantaneously, triggering immediate rebuttals and counterattacks by their adversaries. This “virtual guerilla warfare” is mentally and emotionally exhausting to all involved, especially to the subset of neutral bystanders who are unaffiliated with either political party, which, due to the “religification” of politics, have become like secular religions.5 Chronic, unremitting, inescapable stress is a sure pathway for anxiety, depression, posttraumatic stress disorder, and even brain atrophy.

Optimists may point out that the United States has weathered and emerged stronger from many serious traumas, including the Civil War (with its lethal divisiveness), World War I, the deadly 1918 influenza pandemic, the Great Depression, Pearl Harbor, World War II, the Cold War, the Vietnam War, the Watergate political scandal, the 9/11 terrorist attacks, the banking collapse and recession, and most recently the COVID-19 pandemic, which brought society to a standstill and induced so much anxiety and uncertainty.

On the other hand, pessimists would insist those sequential crises left indelible scars that cumulatively altered the mindset of political rivals, predisposing them to extreme views of each other. Alienation inevitably leads to fanaticism. It’s perplexing but fascinating how the fierce bidirectional missives of weaponized ideas can be as virulent and destructive as a traditional physical war. Perhaps in this era, the pen is mightier than the sword after all.

Continue to: From a psychiatric perspective...

 

 

From a psychiatric perspective, the intransigent groupthink of political partisanship eerily resembles folie en masse, a psychiatric syndrome for which there is no established treatment. It has become a serious threat to our modern democracy. So I decided to ask the “know-it-all” artificial intelligence ChatGPT, whom I previously had “invited” to write a “guest editorial” about myths surrounding psychiatry,6 to answer 3 burning questions:

1. Is there toxic hyperpartisanship in the USA today? (Box 1)

Box 1

Is there toxic hyperpartisanship in the USA today? (generated by ChatGPT)

Yes, there is toxic hyperpartisanship in the United States today. Political polarization has been on the rise for several decades, and in recent years, it has become increasingly toxic and divisive. This toxic hyperpartisanship has contributed to a breakdown in civil discourse and a lack of cooperation and compromise in government.

The toxic hyperpartisanship is evident in many aspects of American society, including politics, media, and social media. Political leaders often engage in divisive rhetoric and focus on winning at all costs, rather than working towards solutions that benefit the country as a whole. Media outlets often present news in a partisan manner, further fueling political polarization. Social media platforms have also played a role in exacerbating toxic hyperpartisanship by allowing the spread of misinformation and creating echo chambers where people are only exposed to like-minded viewpoints.

The consequences of toxic hyperpartisanship are significant, as it can hinder progress on important issues and erode trust in institutions and government. It also makes it difficult for people to engage in productive dialogue and find common ground, leading to a lack of cooperation and compromise.

It is important for individuals to be aware of the impact of toxic hyperpartisanship and work towards finding ways to bridge the political divide and engage in constructive dialogue.

2. How can severe hyperpartisanship be corrected? (Supplemental Box 1)

Supplemental Box 1

How can severe hyperpartisanship be corrected? (generated by ChatGPT)

Severe hyperpartisanship, characterized by intense and entrenched divisions between political parties, can be a challenging issue to address, but there are several steps that can be taken to work towards correcting it. Here are some potential approaches:

1. Promote civil discourse: Encourage respectful and constructive conversations between individuals with differing political views. This can be achieved through education programs, media campaigns, and initiatives to foster open dialogue.

2. Electoral reforms: Consider implementing electoral reforms that can reduce the influence of extreme partisanship. For example, ranked-choice voting or nonpartisan primaries may encourage candidates to appeal to a broader base of voters rather than just their party’s base.

3. Campaign finance reform: Limit the influence of money in politics, as it can exacerbate hyperpartisanship by allowing wealthy donors to have undue influence over candidates and parties.

4. Independent redistricting: Ensure that electoral district boundaries are drawn in a fair and nonpartisan manner. Gerrymandering, the manipulation of district lines to favor one party, can contribute to hyperpartisanship by creating “safe” districts where extreme candidates are more likely to be elected.

5. Promote media literacy: Encourage media literacy education to help citizens critically evaluate information sources and avoid echo chambers. A well-informed electorate is less susceptible to extreme partisanship.

6. Encourage bipartisan collaboration: Highlight and support instances of successful bipartisan collaboration. Elected officials who work across the aisle can serve as positive examples and encourage others to follow suit.

7. Address economic inequality: Tackling economic disparities can alleviate some of the underlying factors that contribute to polarization. When people feel economically secure, they may be more willing to seek common ground.

8. Civics education: Improve civics education in schools to foster a deeper understanding of democratic values, the political process, and the importance of civic engagement.

9. Leadership example: Encourage political leaders to model cooperation and compromise rather than relying on divisive rhetoric. Voters often take cues from their leaders’ behavior.

10. Promote third parties: Support and encourage the emergence of viable thirdparty candidates. A more diverse political landscape can provide alternatives to extreme partisanship.

11. Focus on common ground: Identify and prioritize issues where there is potential for bipartisan consensus and progress. Building success on these issues can create momentum for further cooperation.

12. Encourage grassroots activism: Support grassroots movements that seek to bridge divides and foster understanding between individuals and communities with different political perspectives.

It’s essential to recognize that addressing severe hyperpartisanship is a complex and long-term process that requires collective effort from citizens, political leaders, educators, and institutions. It won’t be achieved overnight, but through sustained and committed actions, progress can be made toward a more collaborative and less divisive political climate.

3. What can cause the collapse of a democracy? (Supplemental Box 2).

Supplemental Box 2

What can cause the collapse of a democracy? (generated by ChatGPT)

The collapse of a democracy can be a complex and multifaceted process, influenced by various factors and circumstances. Some of the common causes that can lead to the erosion or breakdown of a democratic system include:

1. Authoritarianism and power concentration: When leaders or institutions become increasingly authoritarian, centralizing power and weakening checks and balances, it can undermine democratic principles.

2. Corruption and lack of accountability: Rampant corruption among political leaders and institutions can erode public trust in the democratic system, leading to disillusionment and disengagement.

3. Economic instability: Prolonged economic crises or severe inequality can lead to social unrest, increasing the appeal of populist or extremist movements that may challenge democratic norms.

4. Weakening of rule of law: If the rule of law is weakened, and there is a lack of respect for judicial independence and constitutional principles, democratic institutions can become vulnerable to manipulation.

5. Erosion of civil liberties: Suppression of freedom of speech, media, assembly, and association can limit citizens’ ability to express their opinions and participate in the democratic process.

6. Polarization and divisive politics: Extreme political polarization and a breakdown of civil discourse can hinder cooperation and compromise essential for a functioning democracy.

7. External interference: Foreign intervention, propaganda, or cyberattacks can influence electoral processes and undermine democratic institutions.

8. Rise of populism and nationalism: Populist movements that challenge democratic norms, demonize minorities, or advocate for a strongman leadership can pose a threat to democracy.

9. Demographic and social shifts: Demographic changes and social tensions can exacerbate political divisions and weaken the fabric of democratic societies.

10. Lack of civic education and participation: A lack of civic education and low voter turnout can lead to reduced civic engagement and undermine the democratic process.

It is crucial to understand that no democracy is immune to these challenges, and the strength of a democratic system depends on the vigilance and engagement of its citizens, the integrity of its institutions, and the commitment to upholding democratic values. Safeguarding and strengthening democracy requires ongoing efforts to address these issues and protect the principles that underpin democratic governance.

Judge for yourself, but I believe the ChatGPT responses were spot-on.

References

1. Lippard ETC, Nemeroff CB. The devastating clinical consequences of child abuse and neglect: increased disease vulnerability and poor treatment response in mood disorders. Am J Psychiatry. 2023;180(8):548-564.

2. Nemeroff CB. Paradise lost: the neurobiological and clinical consequences of child abuse and neglect. Neuron. 2016;89(5):892-909.

3. Zhang ZZ, Moeckel C, Mustafa M, et al. The association of epigenetic age acceleration and depressive and anxiety symptom severity among children recently exposed to substantiated maltreatment. J Psychiatr Res. 2023;165:7-13.

4. International Churchill Society. The worst form of government. Accessed August 8, 2023. https://winstonchurchill.org/resources/quotes/the-worst-form-of-government/

5. Nasrallah HA. From ideology to articles of faith: the ‘religification’ of political beliefs. Current Psychiatry. 2021;20(7):4-5,19.

6. Nasrallah HA. A ‘guest editorial’ … generated by ChatGPT? Current Psychiatry. 2023;22(4):22:6-7.

References

1. Lippard ETC, Nemeroff CB. The devastating clinical consequences of child abuse and neglect: increased disease vulnerability and poor treatment response in mood disorders. Am J Psychiatry. 2023;180(8):548-564.

2. Nemeroff CB. Paradise lost: the neurobiological and clinical consequences of child abuse and neglect. Neuron. 2016;89(5):892-909.

3. Zhang ZZ, Moeckel C, Mustafa M, et al. The association of epigenetic age acceleration and depressive and anxiety symptom severity among children recently exposed to substantiated maltreatment. J Psychiatr Res. 2023;165:7-13.

4. International Churchill Society. The worst form of government. Accessed August 8, 2023. https://winstonchurchill.org/resources/quotes/the-worst-form-of-government/

5. Nasrallah HA. From ideology to articles of faith: the ‘religification’ of political beliefs. Current Psychiatry. 2021;20(7):4-5,19.

6. Nasrallah HA. A ‘guest editorial’ … generated by ChatGPT? Current Psychiatry. 2023;22(4):22:6-7.

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Crafting a dynamic learning environment during psychiatry clerkships

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Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Creating an optimal learning environment for medical students studying psychiatry is essential for their growth and development. Over the last 25 years, I have worked with hundreds of medical students in a busy urban emergency department (ED), and I have developed a style that has worked well for them and for me. A supportive, engaging atmosphere can significantly enhance students’ understanding of psychiatric conditions, therapeutic approaches, and patient care. To ensure a productive and inspiring learning experience, educators should consider several key factors.

The educators

Faculty physicians should invest themselves in the students’ individual growth and aspirations by providing personalized guidance that caters to each student’s goals and challenges.1 Educators must also embody a passion for psychiatry. I’ve found that integrating a lighthearted and humorous approach to my teaching style can relieve stress and enhance learning. I’ve also found it crucial to demonstrate empathy and effective communication skills that students can emulate in their professional development.2 Encourage students to take an active role in their learning process by engaging in clinical discussions and decision-making. Lastly, providing regular assessments and constructive feedback in a supportive manner allows students to better understand their strengths and weaknesses, and to continually improve their knowledge and skills.3

The students

Encourage students to fully express their unique personalities, perspectives, and learning styles. This diversity can fuel creativity and promote an atmosphere of inclusivity and enhanced learning. Teach students to recognize the value in each patient encounter, because each offers a unique opportunity to deepen their understanding of psychiatric conditions.4 Instead of being mere observers, students should actively participate in their education by involving themselves in clinical discussions, treatment planning, and decision-making.

The environment

A supportive, inclusive learning environment should foster diversity, inclusivity, and collaborative learning by creating an engaging atmosphere in which students can express themselves. In my experience, a sense of relaxed focus can help alleviate stress and enhance creativity. Emphasize a patient-centered approach to instill empathy and compassion in students and enrich their understanding of psychiatric conditions.4

The peers

Encourage students to engage in peer feedback, which will provide their fellow trainees additional perspective on their performance and offer an avenue for constructive criticism and improvement.3 Promoting collaborative learning will foster a sense of camaraderie, help students share their diverse perspectives, and enhance the learning experience. Peers also play a crucial role in reinforcing positive behaviors and attitudes.

My extensive experience educating medical students studying psychiatry in a busy ED has taught me that creating an exceptional learning environment requires understanding the role of educators, students, the environment, and peers. By implementing these principles, educators can contribute to their students’ professional growth, equipping them with the skills and mindset necessary to become a compassionate, competent, effective physician.

References

1. Sutkin G, Wager E, Harris I, et al. What makes a good clinical teacher in medicine? A review of the literature. Acad Med. 2008;83(5):452-466. doi:10.1097/ACM.0b013e31816bee61

2. Passi V, Johnson S, Peile E, et al. Doctor role modelling in medical education: BEME Guide No. 27. Med Teach. 2013;35(9):e1422-e1436. doi:10.3109/0142159X.2013.806982

3. Lerchenfeldt S, Mi M, Eng M. The utilization of peer feedback during collaborative learning in undergraduate medical education: a systematic review. BMC Med Educ. 2019;19(1):321. doi:10.1186/s12909-019-1755-z

4. Bleakley A, Bligh J. Students learning from patients: let’s get real in medical education. Adv Health Sci Educ Theory Pract. 2008;13(1):89-107. doi:10.1007/s10459-006-9028-0

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Dr. Ajluni is Assistant Professor of Psychiatry, Wayne State University, Detroit, Michigan.

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Dr. Ajluni is Assistant Professor of Psychiatry, Wayne State University, Detroit, Michigan.

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Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Creating an optimal learning environment for medical students studying psychiatry is essential for their growth and development. Over the last 25 years, I have worked with hundreds of medical students in a busy urban emergency department (ED), and I have developed a style that has worked well for them and for me. A supportive, engaging atmosphere can significantly enhance students’ understanding of psychiatric conditions, therapeutic approaches, and patient care. To ensure a productive and inspiring learning experience, educators should consider several key factors.

The educators

Faculty physicians should invest themselves in the students’ individual growth and aspirations by providing personalized guidance that caters to each student’s goals and challenges.1 Educators must also embody a passion for psychiatry. I’ve found that integrating a lighthearted and humorous approach to my teaching style can relieve stress and enhance learning. I’ve also found it crucial to demonstrate empathy and effective communication skills that students can emulate in their professional development.2 Encourage students to take an active role in their learning process by engaging in clinical discussions and decision-making. Lastly, providing regular assessments and constructive feedback in a supportive manner allows students to better understand their strengths and weaknesses, and to continually improve their knowledge and skills.3

The students

Encourage students to fully express their unique personalities, perspectives, and learning styles. This diversity can fuel creativity and promote an atmosphere of inclusivity and enhanced learning. Teach students to recognize the value in each patient encounter, because each offers a unique opportunity to deepen their understanding of psychiatric conditions.4 Instead of being mere observers, students should actively participate in their education by involving themselves in clinical discussions, treatment planning, and decision-making.

The environment

A supportive, inclusive learning environment should foster diversity, inclusivity, and collaborative learning by creating an engaging atmosphere in which students can express themselves. In my experience, a sense of relaxed focus can help alleviate stress and enhance creativity. Emphasize a patient-centered approach to instill empathy and compassion in students and enrich their understanding of psychiatric conditions.4

The peers

Encourage students to engage in peer feedback, which will provide their fellow trainees additional perspective on their performance and offer an avenue for constructive criticism and improvement.3 Promoting collaborative learning will foster a sense of camaraderie, help students share their diverse perspectives, and enhance the learning experience. Peers also play a crucial role in reinforcing positive behaviors and attitudes.

My extensive experience educating medical students studying psychiatry in a busy ED has taught me that creating an exceptional learning environment requires understanding the role of educators, students, the environment, and peers. By implementing these principles, educators can contribute to their students’ professional growth, equipping them with the skills and mindset necessary to become a compassionate, competent, effective physician.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Creating an optimal learning environment for medical students studying psychiatry is essential for their growth and development. Over the last 25 years, I have worked with hundreds of medical students in a busy urban emergency department (ED), and I have developed a style that has worked well for them and for me. A supportive, engaging atmosphere can significantly enhance students’ understanding of psychiatric conditions, therapeutic approaches, and patient care. To ensure a productive and inspiring learning experience, educators should consider several key factors.

The educators

Faculty physicians should invest themselves in the students’ individual growth and aspirations by providing personalized guidance that caters to each student’s goals and challenges.1 Educators must also embody a passion for psychiatry. I’ve found that integrating a lighthearted and humorous approach to my teaching style can relieve stress and enhance learning. I’ve also found it crucial to demonstrate empathy and effective communication skills that students can emulate in their professional development.2 Encourage students to take an active role in their learning process by engaging in clinical discussions and decision-making. Lastly, providing regular assessments and constructive feedback in a supportive manner allows students to better understand their strengths and weaknesses, and to continually improve their knowledge and skills.3

The students

Encourage students to fully express their unique personalities, perspectives, and learning styles. This diversity can fuel creativity and promote an atmosphere of inclusivity and enhanced learning. Teach students to recognize the value in each patient encounter, because each offers a unique opportunity to deepen their understanding of psychiatric conditions.4 Instead of being mere observers, students should actively participate in their education by involving themselves in clinical discussions, treatment planning, and decision-making.

The environment

A supportive, inclusive learning environment should foster diversity, inclusivity, and collaborative learning by creating an engaging atmosphere in which students can express themselves. In my experience, a sense of relaxed focus can help alleviate stress and enhance creativity. Emphasize a patient-centered approach to instill empathy and compassion in students and enrich their understanding of psychiatric conditions.4

The peers

Encourage students to engage in peer feedback, which will provide their fellow trainees additional perspective on their performance and offer an avenue for constructive criticism and improvement.3 Promoting collaborative learning will foster a sense of camaraderie, help students share their diverse perspectives, and enhance the learning experience. Peers also play a crucial role in reinforcing positive behaviors and attitudes.

My extensive experience educating medical students studying psychiatry in a busy ED has taught me that creating an exceptional learning environment requires understanding the role of educators, students, the environment, and peers. By implementing these principles, educators can contribute to their students’ professional growth, equipping them with the skills and mindset necessary to become a compassionate, competent, effective physician.

References

1. Sutkin G, Wager E, Harris I, et al. What makes a good clinical teacher in medicine? A review of the literature. Acad Med. 2008;83(5):452-466. doi:10.1097/ACM.0b013e31816bee61

2. Passi V, Johnson S, Peile E, et al. Doctor role modelling in medical education: BEME Guide No. 27. Med Teach. 2013;35(9):e1422-e1436. doi:10.3109/0142159X.2013.806982

3. Lerchenfeldt S, Mi M, Eng M. The utilization of peer feedback during collaborative learning in undergraduate medical education: a systematic review. BMC Med Educ. 2019;19(1):321. doi:10.1186/s12909-019-1755-z

4. Bleakley A, Bligh J. Students learning from patients: let’s get real in medical education. Adv Health Sci Educ Theory Pract. 2008;13(1):89-107. doi:10.1007/s10459-006-9028-0

References

1. Sutkin G, Wager E, Harris I, et al. What makes a good clinical teacher in medicine? A review of the literature. Acad Med. 2008;83(5):452-466. doi:10.1097/ACM.0b013e31816bee61

2. Passi V, Johnson S, Peile E, et al. Doctor role modelling in medical education: BEME Guide No. 27. Med Teach. 2013;35(9):e1422-e1436. doi:10.3109/0142159X.2013.806982

3. Lerchenfeldt S, Mi M, Eng M. The utilization of peer feedback during collaborative learning in undergraduate medical education: a systematic review. BMC Med Educ. 2019;19(1):321. doi:10.1186/s12909-019-1755-z

4. Bleakley A, Bligh J. Students learning from patients: let’s get real in medical education. Adv Health Sci Educ Theory Pract. 2008;13(1):89-107. doi:10.1007/s10459-006-9028-0

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More on prescribing controlled substances

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I was disheartened with the June 2023 issue of Current Psychiatry. This issue included “Optimizing benzodiazepine treatment of anxiety disorders” (p. 22-33,39, doi:10.12788/cp.0365). While these medications may be helpful for short-term treatment, I find their irresponsible use to be a much greater problem than their underutilization.1

The benzodiazepine pharmacology discussed in this article is interesting, but it would be helpful if it had been integrated within a much more extensive discussion of careful prescribing practices. In 2020, the FDA updated the boxed warning to alert prescribers to the serious risks of abuse, addiction, physical dependence, and withdrawal reactions associated with benzodiazepines.2 I would hope that an article on benzodiazepines would provide more discussion and guidance surrounding these important issues.

The June 2023 issue also included “High-dose stimulants for adult ADHD” (p. 34-39, doi:10.12788/cp.0366). This article provided esoteric advice on managing stimulant therapy in the setting of Roux-en-Y gastric bypass surgery, yet I would regard stimulant misuse as a far more common and pressing issue.3,4 The recent Drug Enforcement Administration investigation of telehealth stimulant prescribing is a notable example of this problem.5

The patient discussed in this article was receiving large doses of stimulants for a purported case of refractory attention-deficit/hyperactivity disorder (ADHD). The article provided a sparse differential diagnosis for the patient’s intractable symptoms. While rapid metabolism may be an explanation, I would also like to know how the authors ruled out physiological dependence and/or addiction to a controlled substance. How was misuse excluded? Was urine drug testing (UDS) performed? UDS is highly irregular among prescribers,6 which suggests that practices for detecting covert substance abuse and stimulant misuse are inadequate. Wouldn’t such investigations be fundamental to ethical stimulant prescribing?

Jeff Sanders, MD, PhD
Atlanta, Georgia

References

1. Centers for Disease Control and Prevention. Trends in nonfatal and fatal overdoses involving benzodiazepines—38 states and the District of Columbia, 2019-2020. Accessed August 9, 2023. https://www.cdc.gov/mmwr/volumes/70/wr/mm7034a2.htm

2. US Food & Drug Administration. FDA requiring boxed warning updated to improve safe use of benzodiazepine drug class. Accessed August 14, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class

3. McCabe SE, Schulenberg JE, Wilens TE, et al. Prescription stimulant medical and nonmedical use among US secondary school students, 2005 to 2020. JAMA Netw Open. 2023;6(4):e238707. doi:10.1001/jamanetworkopen.2023.8707

4. US Food & Drug Administration. FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions. Accessed August 14, 2023. https://www.fda.gov/safety/medical-product-safety-information/fda-updating-warnings-improve-safe-use-prescription-stimulants-used-treat-adhd-and-other-conditions

5. Vaidya A. Report: telehealth company’s prescribing practices come under DEA scrutiny. September 16, 2022. Accessed August 9, 2023. https://mhealthintelligence.com/news/report-telehealth-company-dones-prescribing-practices-come-under-dea-scrutiny

6. Zionts A. Some ADHD patients are drug-tested often, while others are never asked. Kaiser Health News. March 25, 2023. Accessed August 9, 2023. https://www.nbcnews.com/news/amp/rcna76330

Continue to: Drs. Stimpfl and Strawn respond

 

 

Drs. Stimpfl and Strawn respond

We thank Dr. Sanders for highlighting the need for clinical equipoise in considering the risks and benefits of medications—something that is true for benzodiazepines, antipsychotics, antidepressants, and in fact all medications. He reminds us that the risks of misuse, dependence, and withdrawal associated with benzodiazepines led to a boxed warning in September 2020 and highlights recent trends of fatal and nonfatal benzodiazepine overdose, especially when combined with opiates.

Our article, which aimed to educate clinicians on benzodiazepine pharma­cology and patient-specific factors influencing benzodiazepine selection and dosing, did not focus significantly on the risks associated with benzodiazepines. We do encourage careful and individualized benzodiazepine prescribing. However, we wish to remind our colleagues that benzodiazepines, while associated with risks, continue to have utility in acute and periprocedural settings, and remain an important treatment option for patients with panic disorder, generalized anxiety disorder (especially while waiting for other medications to take effect), catatonia, seizure disorders, and alcohol withdrawal.

We agree that patient-specific risk assessment is essential, as some patients benefit from benzodiazepines despite the risks. However, we also acknowledge that some individuals are at higher risk for adverse outcomes, including those with concurrent opiate use or who are prescribed other sedative-hypnotics; older adults and those with neurocognitive disorders; and patients susceptible to respiratory depression due to other medical reasons (eg, myasthenia gravis, sleep apnea, and chronic obstructive pulmonary disease). Further, we agree that benzodiazepine use during pregnancy is generally not advised due to the risks of neonatal hypotonia and neonatal withdrawal syndrome1 as well as a possible risk of cleft palate that has been reported in some studies.2 Finally, paradoxical reactions may be more common at the extremes of age and in patients with intellectual disability or personality disorders.3,4

Patient characteristics that have been associated with a higher risk of benzodiazepine use disorder include lower education/income, unemployment, having another substance use disorder, and severe psychopathology.5 In some studies, using benzodiazepines for prolonged periods at high doses as well as using those with a rapid onset of action was associated with an increased risk of benzodiazepine use disorder.5-7

Ultimately, we concur with Dr. Sanders on the perils of the “irresponsible use” of medication and emphasize the need for discernment when choosing treatments to avoid rashly discarding an effective remedy while attempting to mitigate all conceivable risks.

Julia Stimpfl, MD
Jeffrey R. Strawn, MD

Cincinnati, Ohio

References

1. McElhatton PR. The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994;8(6):461-475. doi:10.1016/0890-6238(94)90029-9

2. Enato E, Moretti M, Koren G. The fetal safety of benzodiazepines: an updated meta-analysis. J Obstet Gynaecol Can. 2011;33(1):46-48. doi:10.1016/S1701-2163(16)34772-7 Erratum in: J Obstet Gynaecol Can. 2011;33(4):319.

3. Hakimi Y, Petitpain N, Pinzani V, et al. Paradoxical adverse drug reactions: descriptive analysis of French reports. Eur J Clin Pharmacol. 2020;76(8):1169-1174. doi:10.1007/s00228-020-02892-2

4. Paton C. Benzodiazepines and disinhibition: a review. Psychiatric Bulletin. 2002;26(12):460-462. doi:10.1192/pb.26.12.460

5. Fride Tvete I, Bjørner T, Skomedal T. Risk factors for excessive benzodiazepine use in a working age population: a nationwide 5-year survey in Norway. Scand J Prim Health Care. 2015;33(4):252-259. doi:10.3109/02813432.2015.1117282

6. Griffiths RR, Johnson MW. Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds. J Clin Psychiatry. 2005;66 Suppl 9:31-41.

7. Kan CC, Hilberink SR, Breteler MH. Determination of the main risk factors for benzodiazepine dependence using a multivariate and multidimensional approach. Compr Psychiatry. 2004;45(2):88-94. doi:10.1016/j.comppsych.2003.12.007

Continue to: Drs. Sarma and Grady respond

 

 

Drs. Sarma and Grady respond

Dr. Sanders’ letter highlights the potential caveats associated with prescribing controlled substances. We agree that our short case summary includes numerous interesting elements, each of which would be worthy of further exploration and discussion. Our choice was to highlight the patient history of bariatric surgery and use this as a springboard into a review of stimulants, including the newest formulations for ADHD. For more than 1 year, many generic stimulants have been in short supply, and patients and clinicians have been seeking other therapeutic options. Given this background and with newer, branded stimulant use becoming more commonplace, we believe our article was useful and timely.

Our original intent had been to include an example of a controlled substance agreement. Regrettably, there was simply not enough space for this document or the additional discussion that its inclusion would deem necessary. Nevertheless, had the May 2023 FDA requirement for manufacturers to update the labeling of prescription stimulants1 to clarify misuse and abuse been published before our article’s final revision, we would have mentioned it and provided the appropriate link.

Subbu J. Sarma, MD, FAPA
Kansas City, Missouri

Sarah E. Grady, PharmD, BCPS, BCPP
Des Moines, Iowa

References

1. US Food & Drug Administration. FDA requires updates to clarify labeling of prescription stimulants used to treat ADHD and other conditions. Accessed August 9, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-updates-clarify-labeling-prescription-stimulants-used-treat-adhd-and-other-conditions

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Dr. Strawn has received research support from Abbvie, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the Patient-Centered Outcomes Research Institute. He has served as a consultant for Cerevel, the FDA, Intra-Cellular Therapies, Lundbeck, and Otsuka. He receives royalties from Springer Publishing and UpToDate and received material support from Myriad. He also received honoraria from the American Academy of Child and Adolescent Psychiatry, American Academy of Pediatrics, Medscape Live, and Neuroscience Education Institute. Dr. Strawn is Current Psychiatry ’s Section Editor, Child and Adolescent Psychiatry. Dr. Sarma is a speaker for Idorsia and Teva. The other authors report no financial relationships with any companies whose products are mentioned in their letter or response, or with manufacturers of competing products.

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Dr. Strawn has received research support from Abbvie, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the Patient-Centered Outcomes Research Institute. He has served as a consultant for Cerevel, the FDA, Intra-Cellular Therapies, Lundbeck, and Otsuka. He receives royalties from Springer Publishing and UpToDate and received material support from Myriad. He also received honoraria from the American Academy of Child and Adolescent Psychiatry, American Academy of Pediatrics, Medscape Live, and Neuroscience Education Institute. Dr. Strawn is Current Psychiatry ’s Section Editor, Child and Adolescent Psychiatry. Dr. Sarma is a speaker for Idorsia and Teva. The other authors report no financial relationships with any companies whose products are mentioned in their letter or response, or with manufacturers of competing products.

Author and Disclosure Information

Disclosures
Dr. Strawn has received research support from Abbvie, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the Patient-Centered Outcomes Research Institute. He has served as a consultant for Cerevel, the FDA, Intra-Cellular Therapies, Lundbeck, and Otsuka. He receives royalties from Springer Publishing and UpToDate and received material support from Myriad. He also received honoraria from the American Academy of Child and Adolescent Psychiatry, American Academy of Pediatrics, Medscape Live, and Neuroscience Education Institute. Dr. Strawn is Current Psychiatry ’s Section Editor, Child and Adolescent Psychiatry. Dr. Sarma is a speaker for Idorsia and Teva. The other authors report no financial relationships with any companies whose products are mentioned in their letter or response, or with manufacturers of competing products.

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I was disheartened with the June 2023 issue of Current Psychiatry. This issue included “Optimizing benzodiazepine treatment of anxiety disorders” (p. 22-33,39, doi:10.12788/cp.0365). While these medications may be helpful for short-term treatment, I find their irresponsible use to be a much greater problem than their underutilization.1

The benzodiazepine pharmacology discussed in this article is interesting, but it would be helpful if it had been integrated within a much more extensive discussion of careful prescribing practices. In 2020, the FDA updated the boxed warning to alert prescribers to the serious risks of abuse, addiction, physical dependence, and withdrawal reactions associated with benzodiazepines.2 I would hope that an article on benzodiazepines would provide more discussion and guidance surrounding these important issues.

The June 2023 issue also included “High-dose stimulants for adult ADHD” (p. 34-39, doi:10.12788/cp.0366). This article provided esoteric advice on managing stimulant therapy in the setting of Roux-en-Y gastric bypass surgery, yet I would regard stimulant misuse as a far more common and pressing issue.3,4 The recent Drug Enforcement Administration investigation of telehealth stimulant prescribing is a notable example of this problem.5

The patient discussed in this article was receiving large doses of stimulants for a purported case of refractory attention-deficit/hyperactivity disorder (ADHD). The article provided a sparse differential diagnosis for the patient’s intractable symptoms. While rapid metabolism may be an explanation, I would also like to know how the authors ruled out physiological dependence and/or addiction to a controlled substance. How was misuse excluded? Was urine drug testing (UDS) performed? UDS is highly irregular among prescribers,6 which suggests that practices for detecting covert substance abuse and stimulant misuse are inadequate. Wouldn’t such investigations be fundamental to ethical stimulant prescribing?

Jeff Sanders, MD, PhD
Atlanta, Georgia

References

1. Centers for Disease Control and Prevention. Trends in nonfatal and fatal overdoses involving benzodiazepines—38 states and the District of Columbia, 2019-2020. Accessed August 9, 2023. https://www.cdc.gov/mmwr/volumes/70/wr/mm7034a2.htm

2. US Food & Drug Administration. FDA requiring boxed warning updated to improve safe use of benzodiazepine drug class. Accessed August 14, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class

3. McCabe SE, Schulenberg JE, Wilens TE, et al. Prescription stimulant medical and nonmedical use among US secondary school students, 2005 to 2020. JAMA Netw Open. 2023;6(4):e238707. doi:10.1001/jamanetworkopen.2023.8707

4. US Food & Drug Administration. FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions. Accessed August 14, 2023. https://www.fda.gov/safety/medical-product-safety-information/fda-updating-warnings-improve-safe-use-prescription-stimulants-used-treat-adhd-and-other-conditions

5. Vaidya A. Report: telehealth company’s prescribing practices come under DEA scrutiny. September 16, 2022. Accessed August 9, 2023. https://mhealthintelligence.com/news/report-telehealth-company-dones-prescribing-practices-come-under-dea-scrutiny

6. Zionts A. Some ADHD patients are drug-tested often, while others are never asked. Kaiser Health News. March 25, 2023. Accessed August 9, 2023. https://www.nbcnews.com/news/amp/rcna76330

Continue to: Drs. Stimpfl and Strawn respond

 

 

Drs. Stimpfl and Strawn respond

We thank Dr. Sanders for highlighting the need for clinical equipoise in considering the risks and benefits of medications—something that is true for benzodiazepines, antipsychotics, antidepressants, and in fact all medications. He reminds us that the risks of misuse, dependence, and withdrawal associated with benzodiazepines led to a boxed warning in September 2020 and highlights recent trends of fatal and nonfatal benzodiazepine overdose, especially when combined with opiates.

Our article, which aimed to educate clinicians on benzodiazepine pharma­cology and patient-specific factors influencing benzodiazepine selection and dosing, did not focus significantly on the risks associated with benzodiazepines. We do encourage careful and individualized benzodiazepine prescribing. However, we wish to remind our colleagues that benzodiazepines, while associated with risks, continue to have utility in acute and periprocedural settings, and remain an important treatment option for patients with panic disorder, generalized anxiety disorder (especially while waiting for other medications to take effect), catatonia, seizure disorders, and alcohol withdrawal.

We agree that patient-specific risk assessment is essential, as some patients benefit from benzodiazepines despite the risks. However, we also acknowledge that some individuals are at higher risk for adverse outcomes, including those with concurrent opiate use or who are prescribed other sedative-hypnotics; older adults and those with neurocognitive disorders; and patients susceptible to respiratory depression due to other medical reasons (eg, myasthenia gravis, sleep apnea, and chronic obstructive pulmonary disease). Further, we agree that benzodiazepine use during pregnancy is generally not advised due to the risks of neonatal hypotonia and neonatal withdrawal syndrome1 as well as a possible risk of cleft palate that has been reported in some studies.2 Finally, paradoxical reactions may be more common at the extremes of age and in patients with intellectual disability or personality disorders.3,4

Patient characteristics that have been associated with a higher risk of benzodiazepine use disorder include lower education/income, unemployment, having another substance use disorder, and severe psychopathology.5 In some studies, using benzodiazepines for prolonged periods at high doses as well as using those with a rapid onset of action was associated with an increased risk of benzodiazepine use disorder.5-7

Ultimately, we concur with Dr. Sanders on the perils of the “irresponsible use” of medication and emphasize the need for discernment when choosing treatments to avoid rashly discarding an effective remedy while attempting to mitigate all conceivable risks.

Julia Stimpfl, MD
Jeffrey R. Strawn, MD

Cincinnati, Ohio

References

1. McElhatton PR. The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994;8(6):461-475. doi:10.1016/0890-6238(94)90029-9

2. Enato E, Moretti M, Koren G. The fetal safety of benzodiazepines: an updated meta-analysis. J Obstet Gynaecol Can. 2011;33(1):46-48. doi:10.1016/S1701-2163(16)34772-7 Erratum in: J Obstet Gynaecol Can. 2011;33(4):319.

3. Hakimi Y, Petitpain N, Pinzani V, et al. Paradoxical adverse drug reactions: descriptive analysis of French reports. Eur J Clin Pharmacol. 2020;76(8):1169-1174. doi:10.1007/s00228-020-02892-2

4. Paton C. Benzodiazepines and disinhibition: a review. Psychiatric Bulletin. 2002;26(12):460-462. doi:10.1192/pb.26.12.460

5. Fride Tvete I, Bjørner T, Skomedal T. Risk factors for excessive benzodiazepine use in a working age population: a nationwide 5-year survey in Norway. Scand J Prim Health Care. 2015;33(4):252-259. doi:10.3109/02813432.2015.1117282

6. Griffiths RR, Johnson MW. Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds. J Clin Psychiatry. 2005;66 Suppl 9:31-41.

7. Kan CC, Hilberink SR, Breteler MH. Determination of the main risk factors for benzodiazepine dependence using a multivariate and multidimensional approach. Compr Psychiatry. 2004;45(2):88-94. doi:10.1016/j.comppsych.2003.12.007

Continue to: Drs. Sarma and Grady respond

 

 

Drs. Sarma and Grady respond

Dr. Sanders’ letter highlights the potential caveats associated with prescribing controlled substances. We agree that our short case summary includes numerous interesting elements, each of which would be worthy of further exploration and discussion. Our choice was to highlight the patient history of bariatric surgery and use this as a springboard into a review of stimulants, including the newest formulations for ADHD. For more than 1 year, many generic stimulants have been in short supply, and patients and clinicians have been seeking other therapeutic options. Given this background and with newer, branded stimulant use becoming more commonplace, we believe our article was useful and timely.

Our original intent had been to include an example of a controlled substance agreement. Regrettably, there was simply not enough space for this document or the additional discussion that its inclusion would deem necessary. Nevertheless, had the May 2023 FDA requirement for manufacturers to update the labeling of prescription stimulants1 to clarify misuse and abuse been published before our article’s final revision, we would have mentioned it and provided the appropriate link.

Subbu J. Sarma, MD, FAPA
Kansas City, Missouri

Sarah E. Grady, PharmD, BCPS, BCPP
Des Moines, Iowa

References

1. US Food & Drug Administration. FDA requires updates to clarify labeling of prescription stimulants used to treat ADHD and other conditions. Accessed August 9, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-updates-clarify-labeling-prescription-stimulants-used-treat-adhd-and-other-conditions

I was disheartened with the June 2023 issue of Current Psychiatry. This issue included “Optimizing benzodiazepine treatment of anxiety disorders” (p. 22-33,39, doi:10.12788/cp.0365). While these medications may be helpful for short-term treatment, I find their irresponsible use to be a much greater problem than their underutilization.1

The benzodiazepine pharmacology discussed in this article is interesting, but it would be helpful if it had been integrated within a much more extensive discussion of careful prescribing practices. In 2020, the FDA updated the boxed warning to alert prescribers to the serious risks of abuse, addiction, physical dependence, and withdrawal reactions associated with benzodiazepines.2 I would hope that an article on benzodiazepines would provide more discussion and guidance surrounding these important issues.

The June 2023 issue also included “High-dose stimulants for adult ADHD” (p. 34-39, doi:10.12788/cp.0366). This article provided esoteric advice on managing stimulant therapy in the setting of Roux-en-Y gastric bypass surgery, yet I would regard stimulant misuse as a far more common and pressing issue.3,4 The recent Drug Enforcement Administration investigation of telehealth stimulant prescribing is a notable example of this problem.5

The patient discussed in this article was receiving large doses of stimulants for a purported case of refractory attention-deficit/hyperactivity disorder (ADHD). The article provided a sparse differential diagnosis for the patient’s intractable symptoms. While rapid metabolism may be an explanation, I would also like to know how the authors ruled out physiological dependence and/or addiction to a controlled substance. How was misuse excluded? Was urine drug testing (UDS) performed? UDS is highly irregular among prescribers,6 which suggests that practices for detecting covert substance abuse and stimulant misuse are inadequate. Wouldn’t such investigations be fundamental to ethical stimulant prescribing?

Jeff Sanders, MD, PhD
Atlanta, Georgia

References

1. Centers for Disease Control and Prevention. Trends in nonfatal and fatal overdoses involving benzodiazepines—38 states and the District of Columbia, 2019-2020. Accessed August 9, 2023. https://www.cdc.gov/mmwr/volumes/70/wr/mm7034a2.htm

2. US Food & Drug Administration. FDA requiring boxed warning updated to improve safe use of benzodiazepine drug class. Accessed August 14, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class

3. McCabe SE, Schulenberg JE, Wilens TE, et al. Prescription stimulant medical and nonmedical use among US secondary school students, 2005 to 2020. JAMA Netw Open. 2023;6(4):e238707. doi:10.1001/jamanetworkopen.2023.8707

4. US Food & Drug Administration. FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions. Accessed August 14, 2023. https://www.fda.gov/safety/medical-product-safety-information/fda-updating-warnings-improve-safe-use-prescription-stimulants-used-treat-adhd-and-other-conditions

5. Vaidya A. Report: telehealth company’s prescribing practices come under DEA scrutiny. September 16, 2022. Accessed August 9, 2023. https://mhealthintelligence.com/news/report-telehealth-company-dones-prescribing-practices-come-under-dea-scrutiny

6. Zionts A. Some ADHD patients are drug-tested often, while others are never asked. Kaiser Health News. March 25, 2023. Accessed August 9, 2023. https://www.nbcnews.com/news/amp/rcna76330

Continue to: Drs. Stimpfl and Strawn respond

 

 

Drs. Stimpfl and Strawn respond

We thank Dr. Sanders for highlighting the need for clinical equipoise in considering the risks and benefits of medications—something that is true for benzodiazepines, antipsychotics, antidepressants, and in fact all medications. He reminds us that the risks of misuse, dependence, and withdrawal associated with benzodiazepines led to a boxed warning in September 2020 and highlights recent trends of fatal and nonfatal benzodiazepine overdose, especially when combined with opiates.

Our article, which aimed to educate clinicians on benzodiazepine pharma­cology and patient-specific factors influencing benzodiazepine selection and dosing, did not focus significantly on the risks associated with benzodiazepines. We do encourage careful and individualized benzodiazepine prescribing. However, we wish to remind our colleagues that benzodiazepines, while associated with risks, continue to have utility in acute and periprocedural settings, and remain an important treatment option for patients with panic disorder, generalized anxiety disorder (especially while waiting for other medications to take effect), catatonia, seizure disorders, and alcohol withdrawal.

We agree that patient-specific risk assessment is essential, as some patients benefit from benzodiazepines despite the risks. However, we also acknowledge that some individuals are at higher risk for adverse outcomes, including those with concurrent opiate use or who are prescribed other sedative-hypnotics; older adults and those with neurocognitive disorders; and patients susceptible to respiratory depression due to other medical reasons (eg, myasthenia gravis, sleep apnea, and chronic obstructive pulmonary disease). Further, we agree that benzodiazepine use during pregnancy is generally not advised due to the risks of neonatal hypotonia and neonatal withdrawal syndrome1 as well as a possible risk of cleft palate that has been reported in some studies.2 Finally, paradoxical reactions may be more common at the extremes of age and in patients with intellectual disability or personality disorders.3,4

Patient characteristics that have been associated with a higher risk of benzodiazepine use disorder include lower education/income, unemployment, having another substance use disorder, and severe psychopathology.5 In some studies, using benzodiazepines for prolonged periods at high doses as well as using those with a rapid onset of action was associated with an increased risk of benzodiazepine use disorder.5-7

Ultimately, we concur with Dr. Sanders on the perils of the “irresponsible use” of medication and emphasize the need for discernment when choosing treatments to avoid rashly discarding an effective remedy while attempting to mitigate all conceivable risks.

Julia Stimpfl, MD
Jeffrey R. Strawn, MD

Cincinnati, Ohio

References

1. McElhatton PR. The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994;8(6):461-475. doi:10.1016/0890-6238(94)90029-9

2. Enato E, Moretti M, Koren G. The fetal safety of benzodiazepines: an updated meta-analysis. J Obstet Gynaecol Can. 2011;33(1):46-48. doi:10.1016/S1701-2163(16)34772-7 Erratum in: J Obstet Gynaecol Can. 2011;33(4):319.

3. Hakimi Y, Petitpain N, Pinzani V, et al. Paradoxical adverse drug reactions: descriptive analysis of French reports. Eur J Clin Pharmacol. 2020;76(8):1169-1174. doi:10.1007/s00228-020-02892-2

4. Paton C. Benzodiazepines and disinhibition: a review. Psychiatric Bulletin. 2002;26(12):460-462. doi:10.1192/pb.26.12.460

5. Fride Tvete I, Bjørner T, Skomedal T. Risk factors for excessive benzodiazepine use in a working age population: a nationwide 5-year survey in Norway. Scand J Prim Health Care. 2015;33(4):252-259. doi:10.3109/02813432.2015.1117282

6. Griffiths RR, Johnson MW. Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds. J Clin Psychiatry. 2005;66 Suppl 9:31-41.

7. Kan CC, Hilberink SR, Breteler MH. Determination of the main risk factors for benzodiazepine dependence using a multivariate and multidimensional approach. Compr Psychiatry. 2004;45(2):88-94. doi:10.1016/j.comppsych.2003.12.007

Continue to: Drs. Sarma and Grady respond

 

 

Drs. Sarma and Grady respond

Dr. Sanders’ letter highlights the potential caveats associated with prescribing controlled substances. We agree that our short case summary includes numerous interesting elements, each of which would be worthy of further exploration and discussion. Our choice was to highlight the patient history of bariatric surgery and use this as a springboard into a review of stimulants, including the newest formulations for ADHD. For more than 1 year, many generic stimulants have been in short supply, and patients and clinicians have been seeking other therapeutic options. Given this background and with newer, branded stimulant use becoming more commonplace, we believe our article was useful and timely.

Our original intent had been to include an example of a controlled substance agreement. Regrettably, there was simply not enough space for this document or the additional discussion that its inclusion would deem necessary. Nevertheless, had the May 2023 FDA requirement for manufacturers to update the labeling of prescription stimulants1 to clarify misuse and abuse been published before our article’s final revision, we would have mentioned it and provided the appropriate link.

Subbu J. Sarma, MD, FAPA
Kansas City, Missouri

Sarah E. Grady, PharmD, BCPS, BCPP
Des Moines, Iowa

References

1. US Food & Drug Administration. FDA requires updates to clarify labeling of prescription stimulants used to treat ADHD and other conditions. Accessed August 9, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-updates-clarify-labeling-prescription-stimulants-used-treat-adhd-and-other-conditions

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Introducing the ‘Ethics Corner’

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One of the most rewarding things about serving as editor of GI & Hepatology News is to consider new content that will further engage and bring value to our readership. In addition to reporting on scientific advances from our GI journals that can inform frontline clinical care of patients with gastrointestinal conditions, we have launched several new columns over the past year, including our monthly Member Spotlight and quarterly Health Policy and Advocacy columns, to diversify our content.

Dr. Megan A. Adams

In our September 2023 issue, in addition to debuting a new cover design, we are pleased to introduce yet another new offering – the “Ethics Corner” column. It is intended to highlight important ethical considerations and challenges arising in GI practice and offer practical guidance on how to navigate them. In our inaugural Ethics Corner, AGA Ethics Committee members Dr. Sheldon Sloan and Dr. David Drew discuss the “good, the bad, and the ugly” of direct-to-consumer advertising (DTCA). They highlight the pros and cons of DTCA from an ethical perspective, illustrate how DTCA can impact everyday clinical interactions with patients, and provide insight into how to navigate these challenging conversations. We hope you enjoy this new addition to the newspaper and welcome your ideas for future Ethics Corner columns and other content.

Also in this month’s issue, we update you on AGA’s response to the American College of Physicians’ recent decision to recommend against initiating colon cancer screening at age 45, contrary to the recommendation of the GI community. We also present a story on Humira biosimilars and how they are likely to impact clinical practice. Finally, our September Member Spotlight features GI dietitian Renee Euler, MS, RD, LD, who discusses the intersection between diet and GI disorders, the importance of a team approach to GI care, and her work as a liaison between the AGA and Academy of Nutrition and Dietetics.

We hope you enjoy these, and all the stories featured in our September issue.

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

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One of the most rewarding things about serving as editor of GI & Hepatology News is to consider new content that will further engage and bring value to our readership. In addition to reporting on scientific advances from our GI journals that can inform frontline clinical care of patients with gastrointestinal conditions, we have launched several new columns over the past year, including our monthly Member Spotlight and quarterly Health Policy and Advocacy columns, to diversify our content.

Dr. Megan A. Adams

In our September 2023 issue, in addition to debuting a new cover design, we are pleased to introduce yet another new offering – the “Ethics Corner” column. It is intended to highlight important ethical considerations and challenges arising in GI practice and offer practical guidance on how to navigate them. In our inaugural Ethics Corner, AGA Ethics Committee members Dr. Sheldon Sloan and Dr. David Drew discuss the “good, the bad, and the ugly” of direct-to-consumer advertising (DTCA). They highlight the pros and cons of DTCA from an ethical perspective, illustrate how DTCA can impact everyday clinical interactions with patients, and provide insight into how to navigate these challenging conversations. We hope you enjoy this new addition to the newspaper and welcome your ideas for future Ethics Corner columns and other content.

Also in this month’s issue, we update you on AGA’s response to the American College of Physicians’ recent decision to recommend against initiating colon cancer screening at age 45, contrary to the recommendation of the GI community. We also present a story on Humira biosimilars and how they are likely to impact clinical practice. Finally, our September Member Spotlight features GI dietitian Renee Euler, MS, RD, LD, who discusses the intersection between diet and GI disorders, the importance of a team approach to GI care, and her work as a liaison between the AGA and Academy of Nutrition and Dietetics.

We hope you enjoy these, and all the stories featured in our September issue.

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

One of the most rewarding things about serving as editor of GI & Hepatology News is to consider new content that will further engage and bring value to our readership. In addition to reporting on scientific advances from our GI journals that can inform frontline clinical care of patients with gastrointestinal conditions, we have launched several new columns over the past year, including our monthly Member Spotlight and quarterly Health Policy and Advocacy columns, to diversify our content.

Dr. Megan A. Adams

In our September 2023 issue, in addition to debuting a new cover design, we are pleased to introduce yet another new offering – the “Ethics Corner” column. It is intended to highlight important ethical considerations and challenges arising in GI practice and offer practical guidance on how to navigate them. In our inaugural Ethics Corner, AGA Ethics Committee members Dr. Sheldon Sloan and Dr. David Drew discuss the “good, the bad, and the ugly” of direct-to-consumer advertising (DTCA). They highlight the pros and cons of DTCA from an ethical perspective, illustrate how DTCA can impact everyday clinical interactions with patients, and provide insight into how to navigate these challenging conversations. We hope you enjoy this new addition to the newspaper and welcome your ideas for future Ethics Corner columns and other content.

Also in this month’s issue, we update you on AGA’s response to the American College of Physicians’ recent decision to recommend against initiating colon cancer screening at age 45, contrary to the recommendation of the GI community. We also present a story on Humira biosimilars and how they are likely to impact clinical practice. Finally, our September Member Spotlight features GI dietitian Renee Euler, MS, RD, LD, who discusses the intersection between diet and GI disorders, the importance of a team approach to GI care, and her work as a liaison between the AGA and Academy of Nutrition and Dietetics.

We hope you enjoy these, and all the stories featured in our September issue.

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

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Really? Cancer screening doesn’t save lives?

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This transcript from Impact Factor has been edited for clarity.

If you are my age or older, and like me, you are something of a rule follower, then you’re getting screened for various cancers.

Colonoscopies, mammograms, cervical cancer screening, chest CTs for people with a significant smoking history. The tests are done and usually, but not always, they are negative. And if positive, usually, but not always, follow-up tests are negative, and if they aren’t and a new cancer is diagnosed you tell yourself, Well, at least we caught it early. Isn’t it good that I’m a rule follower? My life was just saved.

But it turns out, proving that cancer screening actually saves lives is quite difficult. Is it possible that all this screening is for nothing?

The benefits, risks, or perhaps futility of cancer screening is in the news this week because of this article, appearing in JAMA Internal Medicine.

It’s a meta-analysis of very specific randomized trials of cancer screening modalities and concludes that, with the exception of sigmoidoscopy for colon cancer screening, none of them meaningfully change life expectancy.

Now – a bit of inside baseball here – I almost never choose to discuss meta-analyses on Impact Factor. It’s hard enough to dig deep into the methodology of a single study, but with a meta-analysis, you’re sort of obligated to review all the included studies, and, what’s worse, the studies that were not included but might bear on the central question.

In this case, though, the topic is important enough to think about a bit more, and the conclusions have large enough implications for public health that we should question them a bit.

First, let’s run down the study as presented.

The authors searched for randomized trials of cancer screening modalities. This is important, and I think appropriate. They wanted studies that took some people and assigned them to screening, and some people to no screening – avoiding the confounding that would come from observational data (rule followers like me tend to live longer owing to a variety of healthful behaviors, not just cancer screening).

Dr. F. Perry Wilson


They didn’t stop at just randomized trials, though. They wanted trials that reported on all-cause, not cancer-specific, mortality. We’ll dig into the distinction in a sec. Finally, they wanted trials with at least 10 years of follow-up time.

These are pretty strict criteria – and after applying that filter, we are left with a grand total of 18 studies to analyze. Most were in the colon cancer space; only two studies met criteria for mammography screening.

Right off the bat, this raises concerns to me. In the universe of high-quality studies of cancer screening modalities, this is just the tip of the iceberg. And the results of meta-analyses are always dependent on the included studies – definitionally.

The results as presented are compelling. None of the individual screening modalities significantly improve life expectancy, except for sigmoidoscopy, which improves it by a whopping 110 days.

JAMA Internal Medicine


(Side note: Averages are tricky here. It’s not like everyone who gets screened gets 110 extra days. Most people get nothing, and some people – those whose colon cancer was detected early – get a bunch of extra days.)

Dr. F. Perry Wilson


And a thing about meta-analysis: Meeting the criteria to be included in a meta-analysis does not necessarily mean the study was a good one. For example, one of the two mammography screening studies included is this one, from Miller and colleagues.

On the surface, it looks good – a large randomized trial of mammography screening in Canada, with long-term follow-up including all-cause mortality. Showing, by the way, no effect of screening on either breast cancer–specific or all-cause mortality.

But that study came under a lot of criticism owing to allegations that randomization was broken and women with palpable breast masses were preferentially put into the mammography group, making those outcomes worse.

The authors of the current meta-analysis don’t mention this. Indeed, they state that they don’t perform any assessments of the quality of the included studies.

But I don’t want to criticize all the included studies. Let’s think bigger picture.

Randomized trials of screening for cancers like colon, breast, and lung cancer in smokers have generally shown that those randomized to screening had lower target-cancer–specific mortality. Across all the randomized mammography studies, for example, women randomized to mammography were about 20% less likely to die of breast cancer than were those who were randomized to not be screened – particularly among those above age 50.

But it’s true that all-cause mortality, on the whole, has not differed statistically between those randomized to mammography vs. no mammography. What’s the deal?

Well, the authors of the meta-analysis engage in some zero-sum thinking here. They say that if it is true that screening tests reduce cancer-specific deaths, but all-cause mortality is not different, screening tests must increase mortality due to other causes. How? They cite colonic perforation during colonoscopy as an example of a harm that could lead to earlier death, which makes some sense. For mammogram and other less invasive screening modalities, they suggest that the stress and anxiety associated with screening might increase the risk for death – this is a bit harder for me to defend.

The thing is, statistics really isn’t a zero-sum game. It’s a question of signal vs. noise. Take breast cancer, for example. Without screening, about 3.2% of women in this country would die of breast cancer. With screening, 2.8% would die (that’s a 20% reduction on the relative scale). The truth is, most women don’t die of breast cancer. Most people don’t die of colon cancer. Even most smokers don’t die of lung cancer. Most people die of heart disease. And then cancer – but there are a lot of cancers out there, and only a handful have decent screening tests.

In other words, the screening tests are unlikely to help most people because most people will not die of the particular type of cancer being screened for. But it will help some small number of those people being screened a lot, potentially saving their lives. If we knew who those people were in advance, it would be great, but then I suppose we wouldn’t need the screening test in the first place.

It’s not fair, then, to say that mammography increases non–breast cancer causes of death. In reality, it’s just that the impact of mammography on all-cause mortality is washed out by the random noise inherent to studying a sample of individuals rather than the entire population.

I’m reminded of that old story about the girl on the beach after a storm, throwing beached starfish back into the water. Someone comes by and says, “Why are you doing that? There are millions of starfish here – it doesn’t matter if you throw a few back.” And she says, “It matters for this one.”

There are other issues with aggregating data like these and concluding that there is no effect on all-cause mortality. For one, it assumes the people randomized to no screening never got screening. Most of these studies lasted 5-10 years, some with longer follow-up, but many people in the no-screening arm may have been screened as recommendations have changed. That would tend to bias the results against screening because the so-called control group, well, isn’t.

It also fails to acknowledge the reality that screening for disease can be thought of as a package deal. Instead of asking whether screening for breast cancer, and colon cancer, and lung cancer individually saves lives, the real relevant question is whether a policy of screening for cancer in general saves lives. And that hasn’t been studied very broadly, except in one trial looking at screening for four cancers. That study is in this meta-analysis and, interestingly, seems to suggest that the policy does extend life – by 123 days. Again, be careful how you think about that average.

I don’t want to be an absolutist here. Whether these screening tests are a good idea or not is actually a moving target. As treatment for cancer gets better, detecting cancer early may not be as important. As new screening modalities emerge, older ones may not be preferable any longer. Better testing, genetic or otherwise, might allow us to tailor screening more narrowly than the population-based approach we have now.

But I worry that a meta-analysis like this, which concludes that screening doesn’t help on the basis of a handful of studies – without acknowledgment of the signal-to-noise problem, without accounting for screening in the control group, without acknowledging that screening should be thought of as a package – will lead some people to make the decision to forgo screening. for, say, 49 out of 50 of them, that may be fine. But for 1 out of 50 or so, well, it matters for that one.
 

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and his new book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

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

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This transcript from Impact Factor has been edited for clarity.

If you are my age or older, and like me, you are something of a rule follower, then you’re getting screened for various cancers.

Colonoscopies, mammograms, cervical cancer screening, chest CTs for people with a significant smoking history. The tests are done and usually, but not always, they are negative. And if positive, usually, but not always, follow-up tests are negative, and if they aren’t and a new cancer is diagnosed you tell yourself, Well, at least we caught it early. Isn’t it good that I’m a rule follower? My life was just saved.

But it turns out, proving that cancer screening actually saves lives is quite difficult. Is it possible that all this screening is for nothing?

The benefits, risks, or perhaps futility of cancer screening is in the news this week because of this article, appearing in JAMA Internal Medicine.

It’s a meta-analysis of very specific randomized trials of cancer screening modalities and concludes that, with the exception of sigmoidoscopy for colon cancer screening, none of them meaningfully change life expectancy.

Now – a bit of inside baseball here – I almost never choose to discuss meta-analyses on Impact Factor. It’s hard enough to dig deep into the methodology of a single study, but with a meta-analysis, you’re sort of obligated to review all the included studies, and, what’s worse, the studies that were not included but might bear on the central question.

In this case, though, the topic is important enough to think about a bit more, and the conclusions have large enough implications for public health that we should question them a bit.

First, let’s run down the study as presented.

The authors searched for randomized trials of cancer screening modalities. This is important, and I think appropriate. They wanted studies that took some people and assigned them to screening, and some people to no screening – avoiding the confounding that would come from observational data (rule followers like me tend to live longer owing to a variety of healthful behaviors, not just cancer screening).

Dr. F. Perry Wilson


They didn’t stop at just randomized trials, though. They wanted trials that reported on all-cause, not cancer-specific, mortality. We’ll dig into the distinction in a sec. Finally, they wanted trials with at least 10 years of follow-up time.

These are pretty strict criteria – and after applying that filter, we are left with a grand total of 18 studies to analyze. Most were in the colon cancer space; only two studies met criteria for mammography screening.

Right off the bat, this raises concerns to me. In the universe of high-quality studies of cancer screening modalities, this is just the tip of the iceberg. And the results of meta-analyses are always dependent on the included studies – definitionally.

The results as presented are compelling. None of the individual screening modalities significantly improve life expectancy, except for sigmoidoscopy, which improves it by a whopping 110 days.

JAMA Internal Medicine


(Side note: Averages are tricky here. It’s not like everyone who gets screened gets 110 extra days. Most people get nothing, and some people – those whose colon cancer was detected early – get a bunch of extra days.)

Dr. F. Perry Wilson


And a thing about meta-analysis: Meeting the criteria to be included in a meta-analysis does not necessarily mean the study was a good one. For example, one of the two mammography screening studies included is this one, from Miller and colleagues.

On the surface, it looks good – a large randomized trial of mammography screening in Canada, with long-term follow-up including all-cause mortality. Showing, by the way, no effect of screening on either breast cancer–specific or all-cause mortality.

But that study came under a lot of criticism owing to allegations that randomization was broken and women with palpable breast masses were preferentially put into the mammography group, making those outcomes worse.

The authors of the current meta-analysis don’t mention this. Indeed, they state that they don’t perform any assessments of the quality of the included studies.

But I don’t want to criticize all the included studies. Let’s think bigger picture.

Randomized trials of screening for cancers like colon, breast, and lung cancer in smokers have generally shown that those randomized to screening had lower target-cancer–specific mortality. Across all the randomized mammography studies, for example, women randomized to mammography were about 20% less likely to die of breast cancer than were those who were randomized to not be screened – particularly among those above age 50.

But it’s true that all-cause mortality, on the whole, has not differed statistically between those randomized to mammography vs. no mammography. What’s the deal?

Well, the authors of the meta-analysis engage in some zero-sum thinking here. They say that if it is true that screening tests reduce cancer-specific deaths, but all-cause mortality is not different, screening tests must increase mortality due to other causes. How? They cite colonic perforation during colonoscopy as an example of a harm that could lead to earlier death, which makes some sense. For mammogram and other less invasive screening modalities, they suggest that the stress and anxiety associated with screening might increase the risk for death – this is a bit harder for me to defend.

The thing is, statistics really isn’t a zero-sum game. It’s a question of signal vs. noise. Take breast cancer, for example. Without screening, about 3.2% of women in this country would die of breast cancer. With screening, 2.8% would die (that’s a 20% reduction on the relative scale). The truth is, most women don’t die of breast cancer. Most people don’t die of colon cancer. Even most smokers don’t die of lung cancer. Most people die of heart disease. And then cancer – but there are a lot of cancers out there, and only a handful have decent screening tests.

In other words, the screening tests are unlikely to help most people because most people will not die of the particular type of cancer being screened for. But it will help some small number of those people being screened a lot, potentially saving their lives. If we knew who those people were in advance, it would be great, but then I suppose we wouldn’t need the screening test in the first place.

It’s not fair, then, to say that mammography increases non–breast cancer causes of death. In reality, it’s just that the impact of mammography on all-cause mortality is washed out by the random noise inherent to studying a sample of individuals rather than the entire population.

I’m reminded of that old story about the girl on the beach after a storm, throwing beached starfish back into the water. Someone comes by and says, “Why are you doing that? There are millions of starfish here – it doesn’t matter if you throw a few back.” And she says, “It matters for this one.”

There are other issues with aggregating data like these and concluding that there is no effect on all-cause mortality. For one, it assumes the people randomized to no screening never got screening. Most of these studies lasted 5-10 years, some with longer follow-up, but many people in the no-screening arm may have been screened as recommendations have changed. That would tend to bias the results against screening because the so-called control group, well, isn’t.

It also fails to acknowledge the reality that screening for disease can be thought of as a package deal. Instead of asking whether screening for breast cancer, and colon cancer, and lung cancer individually saves lives, the real relevant question is whether a policy of screening for cancer in general saves lives. And that hasn’t been studied very broadly, except in one trial looking at screening for four cancers. That study is in this meta-analysis and, interestingly, seems to suggest that the policy does extend life – by 123 days. Again, be careful how you think about that average.

I don’t want to be an absolutist here. Whether these screening tests are a good idea or not is actually a moving target. As treatment for cancer gets better, detecting cancer early may not be as important. As new screening modalities emerge, older ones may not be preferable any longer. Better testing, genetic or otherwise, might allow us to tailor screening more narrowly than the population-based approach we have now.

But I worry that a meta-analysis like this, which concludes that screening doesn’t help on the basis of a handful of studies – without acknowledgment of the signal-to-noise problem, without accounting for screening in the control group, without acknowledging that screening should be thought of as a package – will lead some people to make the decision to forgo screening. for, say, 49 out of 50 of them, that may be fine. But for 1 out of 50 or so, well, it matters for that one.
 

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and his new book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

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

 

This transcript from Impact Factor has been edited for clarity.

If you are my age or older, and like me, you are something of a rule follower, then you’re getting screened for various cancers.

Colonoscopies, mammograms, cervical cancer screening, chest CTs for people with a significant smoking history. The tests are done and usually, but not always, they are negative. And if positive, usually, but not always, follow-up tests are negative, and if they aren’t and a new cancer is diagnosed you tell yourself, Well, at least we caught it early. Isn’t it good that I’m a rule follower? My life was just saved.

But it turns out, proving that cancer screening actually saves lives is quite difficult. Is it possible that all this screening is for nothing?

The benefits, risks, or perhaps futility of cancer screening is in the news this week because of this article, appearing in JAMA Internal Medicine.

It’s a meta-analysis of very specific randomized trials of cancer screening modalities and concludes that, with the exception of sigmoidoscopy for colon cancer screening, none of them meaningfully change life expectancy.

Now – a bit of inside baseball here – I almost never choose to discuss meta-analyses on Impact Factor. It’s hard enough to dig deep into the methodology of a single study, but with a meta-analysis, you’re sort of obligated to review all the included studies, and, what’s worse, the studies that were not included but might bear on the central question.

In this case, though, the topic is important enough to think about a bit more, and the conclusions have large enough implications for public health that we should question them a bit.

First, let’s run down the study as presented.

The authors searched for randomized trials of cancer screening modalities. This is important, and I think appropriate. They wanted studies that took some people and assigned them to screening, and some people to no screening – avoiding the confounding that would come from observational data (rule followers like me tend to live longer owing to a variety of healthful behaviors, not just cancer screening).

Dr. F. Perry Wilson


They didn’t stop at just randomized trials, though. They wanted trials that reported on all-cause, not cancer-specific, mortality. We’ll dig into the distinction in a sec. Finally, they wanted trials with at least 10 years of follow-up time.

These are pretty strict criteria – and after applying that filter, we are left with a grand total of 18 studies to analyze. Most were in the colon cancer space; only two studies met criteria for mammography screening.

Right off the bat, this raises concerns to me. In the universe of high-quality studies of cancer screening modalities, this is just the tip of the iceberg. And the results of meta-analyses are always dependent on the included studies – definitionally.

The results as presented are compelling. None of the individual screening modalities significantly improve life expectancy, except for sigmoidoscopy, which improves it by a whopping 110 days.

JAMA Internal Medicine


(Side note: Averages are tricky here. It’s not like everyone who gets screened gets 110 extra days. Most people get nothing, and some people – those whose colon cancer was detected early – get a bunch of extra days.)

Dr. F. Perry Wilson


And a thing about meta-analysis: Meeting the criteria to be included in a meta-analysis does not necessarily mean the study was a good one. For example, one of the two mammography screening studies included is this one, from Miller and colleagues.

On the surface, it looks good – a large randomized trial of mammography screening in Canada, with long-term follow-up including all-cause mortality. Showing, by the way, no effect of screening on either breast cancer–specific or all-cause mortality.

But that study came under a lot of criticism owing to allegations that randomization was broken and women with palpable breast masses were preferentially put into the mammography group, making those outcomes worse.

The authors of the current meta-analysis don’t mention this. Indeed, they state that they don’t perform any assessments of the quality of the included studies.

But I don’t want to criticize all the included studies. Let’s think bigger picture.

Randomized trials of screening for cancers like colon, breast, and lung cancer in smokers have generally shown that those randomized to screening had lower target-cancer–specific mortality. Across all the randomized mammography studies, for example, women randomized to mammography were about 20% less likely to die of breast cancer than were those who were randomized to not be screened – particularly among those above age 50.

But it’s true that all-cause mortality, on the whole, has not differed statistically between those randomized to mammography vs. no mammography. What’s the deal?

Well, the authors of the meta-analysis engage in some zero-sum thinking here. They say that if it is true that screening tests reduce cancer-specific deaths, but all-cause mortality is not different, screening tests must increase mortality due to other causes. How? They cite colonic perforation during colonoscopy as an example of a harm that could lead to earlier death, which makes some sense. For mammogram and other less invasive screening modalities, they suggest that the stress and anxiety associated with screening might increase the risk for death – this is a bit harder for me to defend.

The thing is, statistics really isn’t a zero-sum game. It’s a question of signal vs. noise. Take breast cancer, for example. Without screening, about 3.2% of women in this country would die of breast cancer. With screening, 2.8% would die (that’s a 20% reduction on the relative scale). The truth is, most women don’t die of breast cancer. Most people don’t die of colon cancer. Even most smokers don’t die of lung cancer. Most people die of heart disease. And then cancer – but there are a lot of cancers out there, and only a handful have decent screening tests.

In other words, the screening tests are unlikely to help most people because most people will not die of the particular type of cancer being screened for. But it will help some small number of those people being screened a lot, potentially saving their lives. If we knew who those people were in advance, it would be great, but then I suppose we wouldn’t need the screening test in the first place.

It’s not fair, then, to say that mammography increases non–breast cancer causes of death. In reality, it’s just that the impact of mammography on all-cause mortality is washed out by the random noise inherent to studying a sample of individuals rather than the entire population.

I’m reminded of that old story about the girl on the beach after a storm, throwing beached starfish back into the water. Someone comes by and says, “Why are you doing that? There are millions of starfish here – it doesn’t matter if you throw a few back.” And she says, “It matters for this one.”

There are other issues with aggregating data like these and concluding that there is no effect on all-cause mortality. For one, it assumes the people randomized to no screening never got screening. Most of these studies lasted 5-10 years, some with longer follow-up, but many people in the no-screening arm may have been screened as recommendations have changed. That would tend to bias the results against screening because the so-called control group, well, isn’t.

It also fails to acknowledge the reality that screening for disease can be thought of as a package deal. Instead of asking whether screening for breast cancer, and colon cancer, and lung cancer individually saves lives, the real relevant question is whether a policy of screening for cancer in general saves lives. And that hasn’t been studied very broadly, except in one trial looking at screening for four cancers. That study is in this meta-analysis and, interestingly, seems to suggest that the policy does extend life – by 123 days. Again, be careful how you think about that average.

I don’t want to be an absolutist here. Whether these screening tests are a good idea or not is actually a moving target. As treatment for cancer gets better, detecting cancer early may not be as important. As new screening modalities emerge, older ones may not be preferable any longer. Better testing, genetic or otherwise, might allow us to tailor screening more narrowly than the population-based approach we have now.

But I worry that a meta-analysis like this, which concludes that screening doesn’t help on the basis of a handful of studies – without acknowledgment of the signal-to-noise problem, without accounting for screening in the control group, without acknowledging that screening should be thought of as a package – will lead some people to make the decision to forgo screening. for, say, 49 out of 50 of them, that may be fine. But for 1 out of 50 or so, well, it matters for that one.
 

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and his new book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

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

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