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COVID-vaccine myocarditis: Rare, mild, and usually in young men
The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”
The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.
That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
Unlikely, brief, and ‘benign’
“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.
In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”
Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.
And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.
Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.
And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.
In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
Males of a certain age
Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.
The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.
In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.
In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”
Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.
In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
Sex hormones may be key
The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.
Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.
“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”
“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”
Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.
Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”
Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”
In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.
Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”
Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
Modulation of immune responses
Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.
“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.
But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”
“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.
Prospects for younger children
Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?
Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.
It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”
A version of this article first appeared on Medscape.com.
The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”
The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.
That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
Unlikely, brief, and ‘benign’
“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.
In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”
Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.
And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.
Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.
And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.
In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
Males of a certain age
Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.
The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.
In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.
In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”
Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.
In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
Sex hormones may be key
The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.
Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.
“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”
“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”
Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.
Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”
Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”
In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.
Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”
Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
Modulation of immune responses
Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.
“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.
But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”
“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.
Prospects for younger children
Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?
Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.
It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”
A version of this article first appeared on Medscape.com.
The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”
The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.
That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
Unlikely, brief, and ‘benign’
“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.
In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”
Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.
And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.
Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.
And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.
In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
Males of a certain age
Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.
The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.
In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.
In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”
Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.
In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
Sex hormones may be key
The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.
Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.
“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”
“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”
Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.
Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”
Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”
In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.
Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”
Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
Modulation of immune responses
Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.
“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.
But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”
“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.
Prospects for younger children
Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?
Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.
It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”
A version of this article first appeared on Medscape.com.
One doctor’s psychedelic journey to confront his cancer
Pradeep Bansal considered the five capsules he was about to swallow. Together they made up a 25-mg dose of a substance that, in another setting, could have landed him in federal prison.
The substance was psilocybin, the active ingredient in magic mushrooms. To be more exact, it was a synthetic form of psilocybin called COMP360, made to pharmaceutical standards by a company called COMPASS Pathways. He was taking it as part of an Food and Drug Administration–approved clinical study on mental health therapy for people with cancer.
Dr. Bansal, a New York gastroenterologist, was far more comfortable giving medical treatment than receiving it. But he was getting used to it.
He had already been through surgery and a number of other treatments to address the physical aspects of his cancer. The psilocybin was to address the mental aspects – the crushing anxiety and depression that had stuck with him after his diagnosis.
Dr. Bansal did not arrive at this moment lightly.
“I was extremely skeptical going into this process,” said Dr. Bansal, who during a long medical career had looked with distrust and even disdain at alternative therapies.
“I don’t have much patience for holistic medicine, homeopathy, acupuncture, or alternative medicines with claims of spiritual upliftment or altered states of mind.”
But Bansal had done his homework on psilocybin and was impressed.
according to studies published in 2011, 2014, and 2016.
One study from Johns Hopkins University tracked the effects of a single guided dose of psilocybin in terminal cancer patients with anxiety and depression. More than 80% had a “significant decrease” in symptoms – even 6 months after treatment – with more than 60% of the group remaining in the normal mood range.
For the study Dr. Bansal joined, there had been weeks of screening and consultation and preparation in a strictly controlled scientific trial.
And yet, even with all that he had learned, even with his psychiatrist-guide by his side, he was afraid. Afraid of what he might experience under the powerful effects of psilocybin. And afraid that this was all a misguided waste of time – that his mental angst would still be there when it was all over.
He knew that psilocybin, like other psychedelic substances, could take you on a “trip” – could remove you, at least for a time, from normal conscious experience.
Maybe he would feel “funny,” he thought. Maybe he would have some hallucinations. But how would that change the reality of his cancer? How would it lift the black dread and anxiety he felt about his future?
Stuck in a dark place
Dr. Bansal had first noticed blood in his urine – a lot of it – in September 2019.
Two months later, doctors diagnosed cancer in his right kidney. He would need surgery to remove the kidney and surrounding lymph nodes (an operation called radical nephrectomy).
It was a shock, said Dr. Bansal. But the diagnosis and the surgery happened so quickly that he hardly had time to think. And treatment results seemed good. The cancer was only in stage I and the CT scans showed no signs of cancer after surgery.
“We were so relieved. Everyone was so happy,” Dr. Bansal said. “They didn’t even give me chemotherapy after surgery because it seemed so early.”
But a routine scan in June 2020 revealed more cancer in his lung. Within a couple of months, it was in his bladder too.
“It was devastating,” Dr. Bansal said. “I went from thinking I was healthy again to stage IV cancer.”
As doctors scheduled surgery to remove part of his lung, Dr. Bansal started on painful immunotherapy (BCG therapy) for his bladder.
At this point, from a psychological standpoint, Dr. Bansal was reeling. As a doctor, he knew all too well the meaning of stage IV cancer.
With two adult children and a grandchild on the way, Dr. Bansal had been looking forward to retirement with his wife of almost 40 years. “Suddenly, I wasn’t sure I was going to last that long,” Bansal recalled. “I was in a very dark place. I was very anxious, very depressed from lack of sleep.”
He saw a therapist about his cancer diagnosis and maintained his regular meditation practice at home. He hired a personal trainer and tried to focus on any good news that he got about his treatment.
Those things helped, but not enough.
The basic facts were inescapable. His cancer might end everything. He couldn’t stop thinking about it. And then he couldn’t stop thinking about how he couldn’t stop thinking about it.
If the worst happened, he didn’t want to spend his last days in a state of such relentless existential angst. And it wasn’t just for himself. He wanted to be strong and mentally present for his family and his loved ones and his patients.
As he searched for something to ease his mental anguish, Dr. Bansal recalled some psychedelic research on end-of-life anxiety and depression that he’d read about in Michael Pollan’s book on psychedelics, “How to Change Your Mind” (New York, Penguin Press, 2018).
The studies were small and the research was new, but Dr. Bansal was impressed enough with the results to take a chance. He called a lead researcher of one of the studies, a fellow New York doctor, and eventually found himself accepted into a new study.
Starting the journey
By the time Dr. Bansal arrived at the Bill Richards Center for Healing at the Aquilino Cancer Center in Rockville, Md., he had already been through weeks of screening.
The main requirements for the study were a cancer diagnosis and a measurable level of depression. But study participants also had to be physically fit enough to handle the medication, and psychologically free from a personal or family history of psychosis or schizophrenia. (The study also required participants to slowly wean themselves from medications like SSRIs for depression or antianxiety medications under the strict supervision of a qualified doctor.)
Dr. Bansal’s week of treatment began almost immediately on arrival at Aquilino. Everything was carefully choreographed but not rushed. From Monday to Wednesday, doctors followed his physical health with exams, ECGs, and blood work. And most importantly, they began to prepare him for the “dosing session” on Thursday when he would take the psilocybin.
This is the careful crafting of “set and setting” stressed in so many psychedelic therapies. “Set” refers to your mindset going into the drug experience. “Setting” is the space and people around you when the drug sends you into an altered state of consciousness.
Dr. Bansal met several times with at least three therapists in the days leading up to his dosing. He attended 4-plus hours of therapist-led group sessions with other people who would get a dosing on the same day. Together, they talked about what to expect during the experience and what to do in the face of fear or panic.
He connected with a therapist who would be his personal guide. Dr. Bansal’s therapist was a military psychiatrist with over 30 years’ experience.
“He was there with me from day 1, and so we established a relationship,” Dr. Bansal said.
“He asked me a lot of personal background history – you know, my religious convictions, aspirations, all those things.”
“Trust and let go,” was a kind of mantra for the treatment repeated by his guide and other doctors.
For Dr. Bansal, a doctor and scientist accustomed to using hard facts rather than touchy-feely slogans to navigate the care of patients, it was an adjustment, to say the least.
But he did his best to set aside his doubts and embrace the journey he was about to take.
The day of the trip
Thursday morning finally arrived. The setting of the dosing room was warm and welcoming, more like a cozy home study than a hospital room.
This matters more than you might think. First, because it’s important that you feel safe, open, and comfortable enough to let go and enter into a therapeutic process. But also because though rare, it’s possible – especially with psilocybin – for people to lose track of where they are and what they’re doing and put themselves or others in danger.
The dose, 25 mg, had been carefully calibrated to induce a psychedelic experience sufficient for therapy. Much less than that, say 10 mg, isn’t enough for most people to enter this state. A double dose, 50 mg, though not physically unsafe, may leave you too incoherent to have the useful insights key to therapeutic value.
A doctor, the lead investigator of the study, brought the five capsules into the room in an intricately carved crucible with a small ceremonial cup that held the water with which to take it.
“It was very solemn,” Dr. Bansal said. “He sat down with me in a very calming way.”
The doctor said: “Don’t worry about it. Just trust and let go.”
And that’s just what he did.
Dr. Bansal swallowed the capsules and lay down. The doctor quietly left the room so that Dr. Bansal and his psychiatrist guide could begin their session together.
Special eye shades kept him in the pitch dark whether his eyes were open or closed. Headphones streamed a curated musical playlist – much of it Western classical like Strauss, Bach, Mozart, and Beethoven – but also modern electronica and other music from cultures around the globe.
Dr. Bansal would remain here, with his therapist-guide by his side, in largely this same position, for the next 7-and-a-half hours.
It took about 45 minutes for the medication to kick in.
The investigator
The doctor who brought the capsules into the dosing room was Manish Agrawal, MD, codirector of clinical research at the Aquilino Cancer Center and lead investigator of the study.
Dr. Agrawal trained at the National Cancer Institute and practiced for many years as an oncologist before developing an interest in psychedelic therapies. It was his work with cancer patients that drew him to psychedelics in the first place.
He had seen too many of his patients mentally wrecked by a cancer diagnosis, and he often felt helpless to comfort them.
“You take care of the physical aspects of the cancer, right? You talk about side effects and recommend another scan to look for recurrence.”
“But what about the psychological effects?”
They can be very serious and too often go ignored, said Dr. Agrawal. Your plans for the future suddenly become moot. You may be concerned about your ability to work or worried about the pain and suffering and financial strain that might be ahead for both you and your family. And to top it all off, you’re staring into the face of your own mortality.
So it’s no wonder, said Dr. Agrawal, that many people develop clinical levels of anxiety and depression after a cancer diagnosis.
Like Dr. Bansal, Dr. Agrawal had been impressed by early studies on psilocybin-assisted therapies for end-of-life anxiety and depression. He had tried other approaches – support groups, one-on-one therapy, religious counselors, psychiatrist-prescribed medication – but he was never really happy with the results.
To Dr. Agrawal, psilocybin-assisted therapy was the first thing that looked like it could really make a difference.
And so after his psychedelic certification at the California Institute of Integral Studies, Dr. Agrawal was determined to change his approach.
The result was the Bill Richards Center for Healing at Aquilino Cancer Center, built specifically to study psychedelic-assisted therapies for psychological distress in people with cancer. The mission of the center is to help develop safe, FDA-approved psychedelic therapies for the mental health of cancer patients, and, once approved, provide a state-of-the-art facility and staff to administer those treatments.
A trip into the unknown
Back in the dosing room, Dr. Bansal was starting to feel the effects of the medication. As the psilocybin kicked in, spectacular images swirled.
“It was as if a million stained glass windows had suddenly come to life and were dancing in front of my vision,” Dr. Bansal said.
There were moving landscapes and intricate swirling patterns and massive stages in the sky where he saw orchestras playing the music he was hearing.
Dr. Bansal saw himself being crushed by a huge machine and buried, dead, in the Earth. He died and returned to life several times, glided over the top of New York City with the skyscrapers just below him, and took in the vision of the entire universe.
“I saw this expanse of the sky that was limitless. And there was this prehistoric reptile creature that spanned galaxies in the sky ahead of me who was dying. I said: ‘My God, the universe is dying,’ but then after a few moments, the universe came to life again in a burst of stars exploding.”
All the while, Dr. Bansal said, he was well aware that it was simply his mind creating these images, thoughts, and ideas. He knew he was in a safe room wearing eyeshades and headphones.
And yet, he says, it felt true. “The images and feelings are so powerful that you cannot help but believe they are in some way a part of reality.”
“At one point, I saw this giant Ferris wheel coming towards me and it was full of giant crabs, clicking and clacking their pincers. And my brain told me: ‘That’s my cancer!’ ”
Dr. Bansal was terrified. But he and his therapist had arranged a system of signals before the session. “If I was feeling afraid, I would hold his hand and if I had other issues, I would raise my hand. If I was feeling good, I would give him a thumbs up.”
Dr. Bansal reached out to his therapist and grasped his hand. “I said, ‘My cancer is coming at me!’ ”
His therapist was clear about what to do: Stand firm and walk toward it.
“That’s what they tell you: If you see anything frightening, you face it. And that’s the whole point of this exercise. And so, I stood and walked forward, and it just blew off in a puff of smoke.”
A state of peace
Around 3 hours into the experience, Dr. Bansal started to feel an immense sense of peace, happiness, and even comfort.
“I felt like I was watching a movie or a multidimensional slideshow. I was also a part of the movie. I felt like I could tell my mind what I wanted to see, and it would show it to me. It’s almost like you can mold your own visions. It was mystical.”
After about 8 hours, as the effects of the drug wore off, Dr. Bansal removed his eyeshades and headphones. He was completely drained.
“Even though I was lying down on my back for 7 hours, I felt like I had been run over by a truck. I was exhausted beyond belief physically and mentally.”
This was partly because of the fact that he hadn’t eaten much during the session. But mostly, said Dr. Bansal, it was because of the searing emotional intensity of the experience.
After the journey
It’s hard to put into words, said Dr. Bansal, what this treatment has done for his life. He feels as if he has stumbled onto something very precious that had been right in front of him all along. He wrote of his change in perspective almost obsessively in his journal in the days and weeks after treatment. One passage reads:
“It seems that, as time is passing on, I’m becoming more relaxed and hopeful, more calm, and at peace. Family has become even more important to me now. Money, politics, material gains, alcohol, seem less important.”
And yet there was nothing “easy” about the experience. In fact, in some ways the experience demanded more from him. “I feel I need to be more compassionate and considerate – less irritable and angry, more understanding of others’ needs. I feel I need to be a better human being, a better patient, a better father, and a better doctor for my patients.”
The experience, he said, gave him something far more important than mere ease. It gave him a sense of meaning.
From his journal:
“I died, and I was reborn. If I survived this, then I can face anything and anybody in the cosmic scheme. I can become part of it.
“How many sorrows in the universe? My cancer is nothing. Life does not end with the end of life. What was will be again. Eternally.”
That’s not an unusual response, according to the namesake of the Bill Richards Center for Healing. Bill Richards, PhD, has worked in the world of psychedelic-assisted psychotherapy since 1963.
A psychologist with decades of experience, Dr. Richards and colleagues figure that, with few possible exceptions, he has helped treat more people with psychedelic therapies than anyone alive in Western medicine today. At Aquilino, he works directly with patients and oversees the therapy protocol that goes along with the psilocybin dosing sessions.
“It’s inspiring,” Dr. Richards said.
“You meet someone who’s very depressed and scared and isolating from family and having all kinds of physical complaints. And a few days later, you talk to the same person and they have a whole new lease on life.”
And the positive effects can extend deep into the family system, he said.
After psilocybin treatment, said Dr. Richards, the person with cancer can become a kind of social worker for the family. They’re often far better able to talk about death and loss and even money and family issues than their loved ones. It’s not uncommon after treatment to see the resolution of years-old resentments or grievances that have dogged a family for many years.
Plus, said Dr. Richards, the cancer patient often ends up as a kind model to other family members for how to approach death. “They can demonstrate how to live fully – right to the last breath – which is a real gift because those relatives and loved ones have to die someday too, you know.”
At 80 years old, Dr. Richards is still in active practice and hopes to spend the rest of his days working with people in end-of-life care.
After the experience
Psychedelic-assisted therapy does not end with the dosing session. Integration sessions, where you discuss what happened during the dosing session, are a key part of most treatments.
The goal is to help participants absorb and “integrate” their experience. It typically happens over two or more sessions of 60-90 minutes with a therapist. In some cases, the therapist may invite a significant other to join in the integration process.
Dr. Agrawal’s trial at the Bill Richards center added something new: group therapy. Not only did Dr. Bansal meet with his therapist, he also met with a group of three other people in the trial who had their dosing the same day.
The point, said Dr. Agrawal, is to try and determine the effect of the group on the therapy. After their private dosing sessions, they come back together to discuss their experiences.
“After the psilocybin, they feel like they’ve been to war together,” Dr. Agrawal said. “There is this profound openness and connection. They feel able to share things with each other that they wouldn’t with other people.”
It will take some time to figure out how the group affects the overall outcome, but Dr. Bansal thinks it was integral to the success of his treatment.
In fact, he continues to meet regularly with his therapy group, even though it’s long since past the requirements of the study.
Pradeep 2.0
Dr. Bansal still has tough days with his cancer. Recently, immunotherapy treatment for his bladder caused side effects – pain, bleeding, fever, and chills – for most of the night. He felt like he was “passing razor blades” when he peed.
“And yet it was somehow okay,” he said. “It was only pain.”
“It’s as if there is a part of me that is watching myself objectively, going through the painful process of treatments saying: ‘It’s all right. I will be with you through this journey, through this experience. Don’t worry.’”
Months after taking that one dose, Dr. Bansal still calls it as “the single most powerful experience of my life.”
The change in his mental outlook, Dr. Bansal said, was profound, particularly in regard to his cancer.
“I understood that I still had cancer and that it could kill me in a few weeks, or months, or years. But my perspective had shifted.”
Dr. Bansal was as surprised as anyone. “Had somebody told me going into this that I would come out a transformed being or a person with a completely different perspective on life, I would never have believed it.”
He even named his new outlook. “I call it Pradeep 2.0.”
A version of this article first appeared on WebMD.com.
Pradeep Bansal considered the five capsules he was about to swallow. Together they made up a 25-mg dose of a substance that, in another setting, could have landed him in federal prison.
The substance was psilocybin, the active ingredient in magic mushrooms. To be more exact, it was a synthetic form of psilocybin called COMP360, made to pharmaceutical standards by a company called COMPASS Pathways. He was taking it as part of an Food and Drug Administration–approved clinical study on mental health therapy for people with cancer.
Dr. Bansal, a New York gastroenterologist, was far more comfortable giving medical treatment than receiving it. But he was getting used to it.
He had already been through surgery and a number of other treatments to address the physical aspects of his cancer. The psilocybin was to address the mental aspects – the crushing anxiety and depression that had stuck with him after his diagnosis.
Dr. Bansal did not arrive at this moment lightly.
“I was extremely skeptical going into this process,” said Dr. Bansal, who during a long medical career had looked with distrust and even disdain at alternative therapies.
“I don’t have much patience for holistic medicine, homeopathy, acupuncture, or alternative medicines with claims of spiritual upliftment or altered states of mind.”
But Bansal had done his homework on psilocybin and was impressed.
according to studies published in 2011, 2014, and 2016.
One study from Johns Hopkins University tracked the effects of a single guided dose of psilocybin in terminal cancer patients with anxiety and depression. More than 80% had a “significant decrease” in symptoms – even 6 months after treatment – with more than 60% of the group remaining in the normal mood range.
For the study Dr. Bansal joined, there had been weeks of screening and consultation and preparation in a strictly controlled scientific trial.
And yet, even with all that he had learned, even with his psychiatrist-guide by his side, he was afraid. Afraid of what he might experience under the powerful effects of psilocybin. And afraid that this was all a misguided waste of time – that his mental angst would still be there when it was all over.
He knew that psilocybin, like other psychedelic substances, could take you on a “trip” – could remove you, at least for a time, from normal conscious experience.
Maybe he would feel “funny,” he thought. Maybe he would have some hallucinations. But how would that change the reality of his cancer? How would it lift the black dread and anxiety he felt about his future?
Stuck in a dark place
Dr. Bansal had first noticed blood in his urine – a lot of it – in September 2019.
Two months later, doctors diagnosed cancer in his right kidney. He would need surgery to remove the kidney and surrounding lymph nodes (an operation called radical nephrectomy).
It was a shock, said Dr. Bansal. But the diagnosis and the surgery happened so quickly that he hardly had time to think. And treatment results seemed good. The cancer was only in stage I and the CT scans showed no signs of cancer after surgery.
“We were so relieved. Everyone was so happy,” Dr. Bansal said. “They didn’t even give me chemotherapy after surgery because it seemed so early.”
But a routine scan in June 2020 revealed more cancer in his lung. Within a couple of months, it was in his bladder too.
“It was devastating,” Dr. Bansal said. “I went from thinking I was healthy again to stage IV cancer.”
As doctors scheduled surgery to remove part of his lung, Dr. Bansal started on painful immunotherapy (BCG therapy) for his bladder.
At this point, from a psychological standpoint, Dr. Bansal was reeling. As a doctor, he knew all too well the meaning of stage IV cancer.
With two adult children and a grandchild on the way, Dr. Bansal had been looking forward to retirement with his wife of almost 40 years. “Suddenly, I wasn’t sure I was going to last that long,” Bansal recalled. “I was in a very dark place. I was very anxious, very depressed from lack of sleep.”
He saw a therapist about his cancer diagnosis and maintained his regular meditation practice at home. He hired a personal trainer and tried to focus on any good news that he got about his treatment.
Those things helped, but not enough.
The basic facts were inescapable. His cancer might end everything. He couldn’t stop thinking about it. And then he couldn’t stop thinking about how he couldn’t stop thinking about it.
If the worst happened, he didn’t want to spend his last days in a state of such relentless existential angst. And it wasn’t just for himself. He wanted to be strong and mentally present for his family and his loved ones and his patients.
As he searched for something to ease his mental anguish, Dr. Bansal recalled some psychedelic research on end-of-life anxiety and depression that he’d read about in Michael Pollan’s book on psychedelics, “How to Change Your Mind” (New York, Penguin Press, 2018).
The studies were small and the research was new, but Dr. Bansal was impressed enough with the results to take a chance. He called a lead researcher of one of the studies, a fellow New York doctor, and eventually found himself accepted into a new study.
Starting the journey
By the time Dr. Bansal arrived at the Bill Richards Center for Healing at the Aquilino Cancer Center in Rockville, Md., he had already been through weeks of screening.
The main requirements for the study were a cancer diagnosis and a measurable level of depression. But study participants also had to be physically fit enough to handle the medication, and psychologically free from a personal or family history of psychosis or schizophrenia. (The study also required participants to slowly wean themselves from medications like SSRIs for depression or antianxiety medications under the strict supervision of a qualified doctor.)
Dr. Bansal’s week of treatment began almost immediately on arrival at Aquilino. Everything was carefully choreographed but not rushed. From Monday to Wednesday, doctors followed his physical health with exams, ECGs, and blood work. And most importantly, they began to prepare him for the “dosing session” on Thursday when he would take the psilocybin.
This is the careful crafting of “set and setting” stressed in so many psychedelic therapies. “Set” refers to your mindset going into the drug experience. “Setting” is the space and people around you when the drug sends you into an altered state of consciousness.
Dr. Bansal met several times with at least three therapists in the days leading up to his dosing. He attended 4-plus hours of therapist-led group sessions with other people who would get a dosing on the same day. Together, they talked about what to expect during the experience and what to do in the face of fear or panic.
He connected with a therapist who would be his personal guide. Dr. Bansal’s therapist was a military psychiatrist with over 30 years’ experience.
“He was there with me from day 1, and so we established a relationship,” Dr. Bansal said.
“He asked me a lot of personal background history – you know, my religious convictions, aspirations, all those things.”
“Trust and let go,” was a kind of mantra for the treatment repeated by his guide and other doctors.
For Dr. Bansal, a doctor and scientist accustomed to using hard facts rather than touchy-feely slogans to navigate the care of patients, it was an adjustment, to say the least.
But he did his best to set aside his doubts and embrace the journey he was about to take.
The day of the trip
Thursday morning finally arrived. The setting of the dosing room was warm and welcoming, more like a cozy home study than a hospital room.
This matters more than you might think. First, because it’s important that you feel safe, open, and comfortable enough to let go and enter into a therapeutic process. But also because though rare, it’s possible – especially with psilocybin – for people to lose track of where they are and what they’re doing and put themselves or others in danger.
The dose, 25 mg, had been carefully calibrated to induce a psychedelic experience sufficient for therapy. Much less than that, say 10 mg, isn’t enough for most people to enter this state. A double dose, 50 mg, though not physically unsafe, may leave you too incoherent to have the useful insights key to therapeutic value.
A doctor, the lead investigator of the study, brought the five capsules into the room in an intricately carved crucible with a small ceremonial cup that held the water with which to take it.
“It was very solemn,” Dr. Bansal said. “He sat down with me in a very calming way.”
The doctor said: “Don’t worry about it. Just trust and let go.”
And that’s just what he did.
Dr. Bansal swallowed the capsules and lay down. The doctor quietly left the room so that Dr. Bansal and his psychiatrist guide could begin their session together.
Special eye shades kept him in the pitch dark whether his eyes were open or closed. Headphones streamed a curated musical playlist – much of it Western classical like Strauss, Bach, Mozart, and Beethoven – but also modern electronica and other music from cultures around the globe.
Dr. Bansal would remain here, with his therapist-guide by his side, in largely this same position, for the next 7-and-a-half hours.
It took about 45 minutes for the medication to kick in.
The investigator
The doctor who brought the capsules into the dosing room was Manish Agrawal, MD, codirector of clinical research at the Aquilino Cancer Center and lead investigator of the study.
Dr. Agrawal trained at the National Cancer Institute and practiced for many years as an oncologist before developing an interest in psychedelic therapies. It was his work with cancer patients that drew him to psychedelics in the first place.
He had seen too many of his patients mentally wrecked by a cancer diagnosis, and he often felt helpless to comfort them.
“You take care of the physical aspects of the cancer, right? You talk about side effects and recommend another scan to look for recurrence.”
“But what about the psychological effects?”
They can be very serious and too often go ignored, said Dr. Agrawal. Your plans for the future suddenly become moot. You may be concerned about your ability to work or worried about the pain and suffering and financial strain that might be ahead for both you and your family. And to top it all off, you’re staring into the face of your own mortality.
So it’s no wonder, said Dr. Agrawal, that many people develop clinical levels of anxiety and depression after a cancer diagnosis.
Like Dr. Bansal, Dr. Agrawal had been impressed by early studies on psilocybin-assisted therapies for end-of-life anxiety and depression. He had tried other approaches – support groups, one-on-one therapy, religious counselors, psychiatrist-prescribed medication – but he was never really happy with the results.
To Dr. Agrawal, psilocybin-assisted therapy was the first thing that looked like it could really make a difference.
And so after his psychedelic certification at the California Institute of Integral Studies, Dr. Agrawal was determined to change his approach.
The result was the Bill Richards Center for Healing at Aquilino Cancer Center, built specifically to study psychedelic-assisted therapies for psychological distress in people with cancer. The mission of the center is to help develop safe, FDA-approved psychedelic therapies for the mental health of cancer patients, and, once approved, provide a state-of-the-art facility and staff to administer those treatments.
A trip into the unknown
Back in the dosing room, Dr. Bansal was starting to feel the effects of the medication. As the psilocybin kicked in, spectacular images swirled.
“It was as if a million stained glass windows had suddenly come to life and were dancing in front of my vision,” Dr. Bansal said.
There were moving landscapes and intricate swirling patterns and massive stages in the sky where he saw orchestras playing the music he was hearing.
Dr. Bansal saw himself being crushed by a huge machine and buried, dead, in the Earth. He died and returned to life several times, glided over the top of New York City with the skyscrapers just below him, and took in the vision of the entire universe.
“I saw this expanse of the sky that was limitless. And there was this prehistoric reptile creature that spanned galaxies in the sky ahead of me who was dying. I said: ‘My God, the universe is dying,’ but then after a few moments, the universe came to life again in a burst of stars exploding.”
All the while, Dr. Bansal said, he was well aware that it was simply his mind creating these images, thoughts, and ideas. He knew he was in a safe room wearing eyeshades and headphones.
And yet, he says, it felt true. “The images and feelings are so powerful that you cannot help but believe they are in some way a part of reality.”
“At one point, I saw this giant Ferris wheel coming towards me and it was full of giant crabs, clicking and clacking their pincers. And my brain told me: ‘That’s my cancer!’ ”
Dr. Bansal was terrified. But he and his therapist had arranged a system of signals before the session. “If I was feeling afraid, I would hold his hand and if I had other issues, I would raise my hand. If I was feeling good, I would give him a thumbs up.”
Dr. Bansal reached out to his therapist and grasped his hand. “I said, ‘My cancer is coming at me!’ ”
His therapist was clear about what to do: Stand firm and walk toward it.
“That’s what they tell you: If you see anything frightening, you face it. And that’s the whole point of this exercise. And so, I stood and walked forward, and it just blew off in a puff of smoke.”
A state of peace
Around 3 hours into the experience, Dr. Bansal started to feel an immense sense of peace, happiness, and even comfort.
“I felt like I was watching a movie or a multidimensional slideshow. I was also a part of the movie. I felt like I could tell my mind what I wanted to see, and it would show it to me. It’s almost like you can mold your own visions. It was mystical.”
After about 8 hours, as the effects of the drug wore off, Dr. Bansal removed his eyeshades and headphones. He was completely drained.
“Even though I was lying down on my back for 7 hours, I felt like I had been run over by a truck. I was exhausted beyond belief physically and mentally.”
This was partly because of the fact that he hadn’t eaten much during the session. But mostly, said Dr. Bansal, it was because of the searing emotional intensity of the experience.
After the journey
It’s hard to put into words, said Dr. Bansal, what this treatment has done for his life. He feels as if he has stumbled onto something very precious that had been right in front of him all along. He wrote of his change in perspective almost obsessively in his journal in the days and weeks after treatment. One passage reads:
“It seems that, as time is passing on, I’m becoming more relaxed and hopeful, more calm, and at peace. Family has become even more important to me now. Money, politics, material gains, alcohol, seem less important.”
And yet there was nothing “easy” about the experience. In fact, in some ways the experience demanded more from him. “I feel I need to be more compassionate and considerate – less irritable and angry, more understanding of others’ needs. I feel I need to be a better human being, a better patient, a better father, and a better doctor for my patients.”
The experience, he said, gave him something far more important than mere ease. It gave him a sense of meaning.
From his journal:
“I died, and I was reborn. If I survived this, then I can face anything and anybody in the cosmic scheme. I can become part of it.
“How many sorrows in the universe? My cancer is nothing. Life does not end with the end of life. What was will be again. Eternally.”
That’s not an unusual response, according to the namesake of the Bill Richards Center for Healing. Bill Richards, PhD, has worked in the world of psychedelic-assisted psychotherapy since 1963.
A psychologist with decades of experience, Dr. Richards and colleagues figure that, with few possible exceptions, he has helped treat more people with psychedelic therapies than anyone alive in Western medicine today. At Aquilino, he works directly with patients and oversees the therapy protocol that goes along with the psilocybin dosing sessions.
“It’s inspiring,” Dr. Richards said.
“You meet someone who’s very depressed and scared and isolating from family and having all kinds of physical complaints. And a few days later, you talk to the same person and they have a whole new lease on life.”
And the positive effects can extend deep into the family system, he said.
After psilocybin treatment, said Dr. Richards, the person with cancer can become a kind of social worker for the family. They’re often far better able to talk about death and loss and even money and family issues than their loved ones. It’s not uncommon after treatment to see the resolution of years-old resentments or grievances that have dogged a family for many years.
Plus, said Dr. Richards, the cancer patient often ends up as a kind model to other family members for how to approach death. “They can demonstrate how to live fully – right to the last breath – which is a real gift because those relatives and loved ones have to die someday too, you know.”
At 80 years old, Dr. Richards is still in active practice and hopes to spend the rest of his days working with people in end-of-life care.
After the experience
Psychedelic-assisted therapy does not end with the dosing session. Integration sessions, where you discuss what happened during the dosing session, are a key part of most treatments.
The goal is to help participants absorb and “integrate” their experience. It typically happens over two or more sessions of 60-90 minutes with a therapist. In some cases, the therapist may invite a significant other to join in the integration process.
Dr. Agrawal’s trial at the Bill Richards center added something new: group therapy. Not only did Dr. Bansal meet with his therapist, he also met with a group of three other people in the trial who had their dosing the same day.
The point, said Dr. Agrawal, is to try and determine the effect of the group on the therapy. After their private dosing sessions, they come back together to discuss their experiences.
“After the psilocybin, they feel like they’ve been to war together,” Dr. Agrawal said. “There is this profound openness and connection. They feel able to share things with each other that they wouldn’t with other people.”
It will take some time to figure out how the group affects the overall outcome, but Dr. Bansal thinks it was integral to the success of his treatment.
In fact, he continues to meet regularly with his therapy group, even though it’s long since past the requirements of the study.
Pradeep 2.0
Dr. Bansal still has tough days with his cancer. Recently, immunotherapy treatment for his bladder caused side effects – pain, bleeding, fever, and chills – for most of the night. He felt like he was “passing razor blades” when he peed.
“And yet it was somehow okay,” he said. “It was only pain.”
“It’s as if there is a part of me that is watching myself objectively, going through the painful process of treatments saying: ‘It’s all right. I will be with you through this journey, through this experience. Don’t worry.’”
Months after taking that one dose, Dr. Bansal still calls it as “the single most powerful experience of my life.”
The change in his mental outlook, Dr. Bansal said, was profound, particularly in regard to his cancer.
“I understood that I still had cancer and that it could kill me in a few weeks, or months, or years. But my perspective had shifted.”
Dr. Bansal was as surprised as anyone. “Had somebody told me going into this that I would come out a transformed being or a person with a completely different perspective on life, I would never have believed it.”
He even named his new outlook. “I call it Pradeep 2.0.”
A version of this article first appeared on WebMD.com.
Pradeep Bansal considered the five capsules he was about to swallow. Together they made up a 25-mg dose of a substance that, in another setting, could have landed him in federal prison.
The substance was psilocybin, the active ingredient in magic mushrooms. To be more exact, it was a synthetic form of psilocybin called COMP360, made to pharmaceutical standards by a company called COMPASS Pathways. He was taking it as part of an Food and Drug Administration–approved clinical study on mental health therapy for people with cancer.
Dr. Bansal, a New York gastroenterologist, was far more comfortable giving medical treatment than receiving it. But he was getting used to it.
He had already been through surgery and a number of other treatments to address the physical aspects of his cancer. The psilocybin was to address the mental aspects – the crushing anxiety and depression that had stuck with him after his diagnosis.
Dr. Bansal did not arrive at this moment lightly.
“I was extremely skeptical going into this process,” said Dr. Bansal, who during a long medical career had looked with distrust and even disdain at alternative therapies.
“I don’t have much patience for holistic medicine, homeopathy, acupuncture, or alternative medicines with claims of spiritual upliftment or altered states of mind.”
But Bansal had done his homework on psilocybin and was impressed.
according to studies published in 2011, 2014, and 2016.
One study from Johns Hopkins University tracked the effects of a single guided dose of psilocybin in terminal cancer patients with anxiety and depression. More than 80% had a “significant decrease” in symptoms – even 6 months after treatment – with more than 60% of the group remaining in the normal mood range.
For the study Dr. Bansal joined, there had been weeks of screening and consultation and preparation in a strictly controlled scientific trial.
And yet, even with all that he had learned, even with his psychiatrist-guide by his side, he was afraid. Afraid of what he might experience under the powerful effects of psilocybin. And afraid that this was all a misguided waste of time – that his mental angst would still be there when it was all over.
He knew that psilocybin, like other psychedelic substances, could take you on a “trip” – could remove you, at least for a time, from normal conscious experience.
Maybe he would feel “funny,” he thought. Maybe he would have some hallucinations. But how would that change the reality of his cancer? How would it lift the black dread and anxiety he felt about his future?
Stuck in a dark place
Dr. Bansal had first noticed blood in his urine – a lot of it – in September 2019.
Two months later, doctors diagnosed cancer in his right kidney. He would need surgery to remove the kidney and surrounding lymph nodes (an operation called radical nephrectomy).
It was a shock, said Dr. Bansal. But the diagnosis and the surgery happened so quickly that he hardly had time to think. And treatment results seemed good. The cancer was only in stage I and the CT scans showed no signs of cancer after surgery.
“We were so relieved. Everyone was so happy,” Dr. Bansal said. “They didn’t even give me chemotherapy after surgery because it seemed so early.”
But a routine scan in June 2020 revealed more cancer in his lung. Within a couple of months, it was in his bladder too.
“It was devastating,” Dr. Bansal said. “I went from thinking I was healthy again to stage IV cancer.”
As doctors scheduled surgery to remove part of his lung, Dr. Bansal started on painful immunotherapy (BCG therapy) for his bladder.
At this point, from a psychological standpoint, Dr. Bansal was reeling. As a doctor, he knew all too well the meaning of stage IV cancer.
With two adult children and a grandchild on the way, Dr. Bansal had been looking forward to retirement with his wife of almost 40 years. “Suddenly, I wasn’t sure I was going to last that long,” Bansal recalled. “I was in a very dark place. I was very anxious, very depressed from lack of sleep.”
He saw a therapist about his cancer diagnosis and maintained his regular meditation practice at home. He hired a personal trainer and tried to focus on any good news that he got about his treatment.
Those things helped, but not enough.
The basic facts were inescapable. His cancer might end everything. He couldn’t stop thinking about it. And then he couldn’t stop thinking about how he couldn’t stop thinking about it.
If the worst happened, he didn’t want to spend his last days in a state of such relentless existential angst. And it wasn’t just for himself. He wanted to be strong and mentally present for his family and his loved ones and his patients.
As he searched for something to ease his mental anguish, Dr. Bansal recalled some psychedelic research on end-of-life anxiety and depression that he’d read about in Michael Pollan’s book on psychedelics, “How to Change Your Mind” (New York, Penguin Press, 2018).
The studies were small and the research was new, but Dr. Bansal was impressed enough with the results to take a chance. He called a lead researcher of one of the studies, a fellow New York doctor, and eventually found himself accepted into a new study.
Starting the journey
By the time Dr. Bansal arrived at the Bill Richards Center for Healing at the Aquilino Cancer Center in Rockville, Md., he had already been through weeks of screening.
The main requirements for the study were a cancer diagnosis and a measurable level of depression. But study participants also had to be physically fit enough to handle the medication, and psychologically free from a personal or family history of psychosis or schizophrenia. (The study also required participants to slowly wean themselves from medications like SSRIs for depression or antianxiety medications under the strict supervision of a qualified doctor.)
Dr. Bansal’s week of treatment began almost immediately on arrival at Aquilino. Everything was carefully choreographed but not rushed. From Monday to Wednesday, doctors followed his physical health with exams, ECGs, and blood work. And most importantly, they began to prepare him for the “dosing session” on Thursday when he would take the psilocybin.
This is the careful crafting of “set and setting” stressed in so many psychedelic therapies. “Set” refers to your mindset going into the drug experience. “Setting” is the space and people around you when the drug sends you into an altered state of consciousness.
Dr. Bansal met several times with at least three therapists in the days leading up to his dosing. He attended 4-plus hours of therapist-led group sessions with other people who would get a dosing on the same day. Together, they talked about what to expect during the experience and what to do in the face of fear or panic.
He connected with a therapist who would be his personal guide. Dr. Bansal’s therapist was a military psychiatrist with over 30 years’ experience.
“He was there with me from day 1, and so we established a relationship,” Dr. Bansal said.
“He asked me a lot of personal background history – you know, my religious convictions, aspirations, all those things.”
“Trust and let go,” was a kind of mantra for the treatment repeated by his guide and other doctors.
For Dr. Bansal, a doctor and scientist accustomed to using hard facts rather than touchy-feely slogans to navigate the care of patients, it was an adjustment, to say the least.
But he did his best to set aside his doubts and embrace the journey he was about to take.
The day of the trip
Thursday morning finally arrived. The setting of the dosing room was warm and welcoming, more like a cozy home study than a hospital room.
This matters more than you might think. First, because it’s important that you feel safe, open, and comfortable enough to let go and enter into a therapeutic process. But also because though rare, it’s possible – especially with psilocybin – for people to lose track of where they are and what they’re doing and put themselves or others in danger.
The dose, 25 mg, had been carefully calibrated to induce a psychedelic experience sufficient for therapy. Much less than that, say 10 mg, isn’t enough for most people to enter this state. A double dose, 50 mg, though not physically unsafe, may leave you too incoherent to have the useful insights key to therapeutic value.
A doctor, the lead investigator of the study, brought the five capsules into the room in an intricately carved crucible with a small ceremonial cup that held the water with which to take it.
“It was very solemn,” Dr. Bansal said. “He sat down with me in a very calming way.”
The doctor said: “Don’t worry about it. Just trust and let go.”
And that’s just what he did.
Dr. Bansal swallowed the capsules and lay down. The doctor quietly left the room so that Dr. Bansal and his psychiatrist guide could begin their session together.
Special eye shades kept him in the pitch dark whether his eyes were open or closed. Headphones streamed a curated musical playlist – much of it Western classical like Strauss, Bach, Mozart, and Beethoven – but also modern electronica and other music from cultures around the globe.
Dr. Bansal would remain here, with his therapist-guide by his side, in largely this same position, for the next 7-and-a-half hours.
It took about 45 minutes for the medication to kick in.
The investigator
The doctor who brought the capsules into the dosing room was Manish Agrawal, MD, codirector of clinical research at the Aquilino Cancer Center and lead investigator of the study.
Dr. Agrawal trained at the National Cancer Institute and practiced for many years as an oncologist before developing an interest in psychedelic therapies. It was his work with cancer patients that drew him to psychedelics in the first place.
He had seen too many of his patients mentally wrecked by a cancer diagnosis, and he often felt helpless to comfort them.
“You take care of the physical aspects of the cancer, right? You talk about side effects and recommend another scan to look for recurrence.”
“But what about the psychological effects?”
They can be very serious and too often go ignored, said Dr. Agrawal. Your plans for the future suddenly become moot. You may be concerned about your ability to work or worried about the pain and suffering and financial strain that might be ahead for both you and your family. And to top it all off, you’re staring into the face of your own mortality.
So it’s no wonder, said Dr. Agrawal, that many people develop clinical levels of anxiety and depression after a cancer diagnosis.
Like Dr. Bansal, Dr. Agrawal had been impressed by early studies on psilocybin-assisted therapies for end-of-life anxiety and depression. He had tried other approaches – support groups, one-on-one therapy, religious counselors, psychiatrist-prescribed medication – but he was never really happy with the results.
To Dr. Agrawal, psilocybin-assisted therapy was the first thing that looked like it could really make a difference.
And so after his psychedelic certification at the California Institute of Integral Studies, Dr. Agrawal was determined to change his approach.
The result was the Bill Richards Center for Healing at Aquilino Cancer Center, built specifically to study psychedelic-assisted therapies for psychological distress in people with cancer. The mission of the center is to help develop safe, FDA-approved psychedelic therapies for the mental health of cancer patients, and, once approved, provide a state-of-the-art facility and staff to administer those treatments.
A trip into the unknown
Back in the dosing room, Dr. Bansal was starting to feel the effects of the medication. As the psilocybin kicked in, spectacular images swirled.
“It was as if a million stained glass windows had suddenly come to life and were dancing in front of my vision,” Dr. Bansal said.
There were moving landscapes and intricate swirling patterns and massive stages in the sky where he saw orchestras playing the music he was hearing.
Dr. Bansal saw himself being crushed by a huge machine and buried, dead, in the Earth. He died and returned to life several times, glided over the top of New York City with the skyscrapers just below him, and took in the vision of the entire universe.
“I saw this expanse of the sky that was limitless. And there was this prehistoric reptile creature that spanned galaxies in the sky ahead of me who was dying. I said: ‘My God, the universe is dying,’ but then after a few moments, the universe came to life again in a burst of stars exploding.”
All the while, Dr. Bansal said, he was well aware that it was simply his mind creating these images, thoughts, and ideas. He knew he was in a safe room wearing eyeshades and headphones.
And yet, he says, it felt true. “The images and feelings are so powerful that you cannot help but believe they are in some way a part of reality.”
“At one point, I saw this giant Ferris wheel coming towards me and it was full of giant crabs, clicking and clacking their pincers. And my brain told me: ‘That’s my cancer!’ ”
Dr. Bansal was terrified. But he and his therapist had arranged a system of signals before the session. “If I was feeling afraid, I would hold his hand and if I had other issues, I would raise my hand. If I was feeling good, I would give him a thumbs up.”
Dr. Bansal reached out to his therapist and grasped his hand. “I said, ‘My cancer is coming at me!’ ”
His therapist was clear about what to do: Stand firm and walk toward it.
“That’s what they tell you: If you see anything frightening, you face it. And that’s the whole point of this exercise. And so, I stood and walked forward, and it just blew off in a puff of smoke.”
A state of peace
Around 3 hours into the experience, Dr. Bansal started to feel an immense sense of peace, happiness, and even comfort.
“I felt like I was watching a movie or a multidimensional slideshow. I was also a part of the movie. I felt like I could tell my mind what I wanted to see, and it would show it to me. It’s almost like you can mold your own visions. It was mystical.”
After about 8 hours, as the effects of the drug wore off, Dr. Bansal removed his eyeshades and headphones. He was completely drained.
“Even though I was lying down on my back for 7 hours, I felt like I had been run over by a truck. I was exhausted beyond belief physically and mentally.”
This was partly because of the fact that he hadn’t eaten much during the session. But mostly, said Dr. Bansal, it was because of the searing emotional intensity of the experience.
After the journey
It’s hard to put into words, said Dr. Bansal, what this treatment has done for his life. He feels as if he has stumbled onto something very precious that had been right in front of him all along. He wrote of his change in perspective almost obsessively in his journal in the days and weeks after treatment. One passage reads:
“It seems that, as time is passing on, I’m becoming more relaxed and hopeful, more calm, and at peace. Family has become even more important to me now. Money, politics, material gains, alcohol, seem less important.”
And yet there was nothing “easy” about the experience. In fact, in some ways the experience demanded more from him. “I feel I need to be more compassionate and considerate – less irritable and angry, more understanding of others’ needs. I feel I need to be a better human being, a better patient, a better father, and a better doctor for my patients.”
The experience, he said, gave him something far more important than mere ease. It gave him a sense of meaning.
From his journal:
“I died, and I was reborn. If I survived this, then I can face anything and anybody in the cosmic scheme. I can become part of it.
“How many sorrows in the universe? My cancer is nothing. Life does not end with the end of life. What was will be again. Eternally.”
That’s not an unusual response, according to the namesake of the Bill Richards Center for Healing. Bill Richards, PhD, has worked in the world of psychedelic-assisted psychotherapy since 1963.
A psychologist with decades of experience, Dr. Richards and colleagues figure that, with few possible exceptions, he has helped treat more people with psychedelic therapies than anyone alive in Western medicine today. At Aquilino, he works directly with patients and oversees the therapy protocol that goes along with the psilocybin dosing sessions.
“It’s inspiring,” Dr. Richards said.
“You meet someone who’s very depressed and scared and isolating from family and having all kinds of physical complaints. And a few days later, you talk to the same person and they have a whole new lease on life.”
And the positive effects can extend deep into the family system, he said.
After psilocybin treatment, said Dr. Richards, the person with cancer can become a kind of social worker for the family. They’re often far better able to talk about death and loss and even money and family issues than their loved ones. It’s not uncommon after treatment to see the resolution of years-old resentments or grievances that have dogged a family for many years.
Plus, said Dr. Richards, the cancer patient often ends up as a kind model to other family members for how to approach death. “They can demonstrate how to live fully – right to the last breath – which is a real gift because those relatives and loved ones have to die someday too, you know.”
At 80 years old, Dr. Richards is still in active practice and hopes to spend the rest of his days working with people in end-of-life care.
After the experience
Psychedelic-assisted therapy does not end with the dosing session. Integration sessions, where you discuss what happened during the dosing session, are a key part of most treatments.
The goal is to help participants absorb and “integrate” their experience. It typically happens over two or more sessions of 60-90 minutes with a therapist. In some cases, the therapist may invite a significant other to join in the integration process.
Dr. Agrawal’s trial at the Bill Richards center added something new: group therapy. Not only did Dr. Bansal meet with his therapist, he also met with a group of three other people in the trial who had their dosing the same day.
The point, said Dr. Agrawal, is to try and determine the effect of the group on the therapy. After their private dosing sessions, they come back together to discuss their experiences.
“After the psilocybin, they feel like they’ve been to war together,” Dr. Agrawal said. “There is this profound openness and connection. They feel able to share things with each other that they wouldn’t with other people.”
It will take some time to figure out how the group affects the overall outcome, but Dr. Bansal thinks it was integral to the success of his treatment.
In fact, he continues to meet regularly with his therapy group, even though it’s long since past the requirements of the study.
Pradeep 2.0
Dr. Bansal still has tough days with his cancer. Recently, immunotherapy treatment for his bladder caused side effects – pain, bleeding, fever, and chills – for most of the night. He felt like he was “passing razor blades” when he peed.
“And yet it was somehow okay,” he said. “It was only pain.”
“It’s as if there is a part of me that is watching myself objectively, going through the painful process of treatments saying: ‘It’s all right. I will be with you through this journey, through this experience. Don’t worry.’”
Months after taking that one dose, Dr. Bansal still calls it as “the single most powerful experience of my life.”
The change in his mental outlook, Dr. Bansal said, was profound, particularly in regard to his cancer.
“I understood that I still had cancer and that it could kill me in a few weeks, or months, or years. But my perspective had shifted.”
Dr. Bansal was as surprised as anyone. “Had somebody told me going into this that I would come out a transformed being or a person with a completely different perspective on life, I would never have believed it.”
He even named his new outlook. “I call it Pradeep 2.0.”
A version of this article first appeared on WebMD.com.
My favorite physical exam pearls
I would like to start the new year off by returning to the past – when the physical exam was emphasized and utilized in decision making. I think a big reason that its use has diminished in recent years is due to the physical exam not having been emphasized in training.
For those seeking to increase their comfort with conducting the physical exam, below are several methods I have found helpful to use in practice.
Examining the pharynx
We were usually taught to ask the patient to say ahhh, with or without a nasty tongue depressor.
When I was on my pediatrics rotation, I was taught to ask the patients to roar like a lion, which always gave a nice look at their posterior pharynx. The kids also really liked doing this, but it might seem a little strange to ask adults to do this.
A technique I have found that works well with adults is to ask them to yawn. I have found that this get me a great look at the pharynx for about half of my patients.
Auscultatory percussion for pleural effusions
Guarino and colleagues described a technique that is easily mastered and very effective for determining the presence of pleural effusions.1 It involves placing the stethoscope 3 cm below the last rib in the mid clavicular line and tapping from the apex down to the last rib.
For patients without effusion, a sharp change to a loud percussion note will occur at the last rib.
If the patient has an effusion, the loud percussion note will start at the top of the effusion.
This method was remarkably successful at finding pleural effusions. In the study, Dr. Guarino found a sensitivity of 96% and a specificity of 100%.
Physical exam for anemia
Look at the nails and see if they look pale. How can we do this?
The first step is to know what your own hematocrit is. You can then compare the color of your nail to that of the patient.
If you have a normal hematocrit and the patient’s nail bed color is lighter than yours, the patient likely has anemia. If you do this frequently, you will get good at estimating hematocrit. This is especially important if you do not have labs readily available.
Another way to assess for anemia is to look at the color tint of the lower conjunctiva. The best way to look for this is to look at whether there is a generous amount of visible capillaries in the lower conjunctiva. Patients without anemia have a darker red color because of these vessels, whereas patients with anemia are a lighter pink.
Strobach and colleagues2 looked at both nail bed rubor and color tint of the lower conjunctiva and found that both reliably predicted presence and degree of anemia.
Determining if clubbing is present
Most physicians are aware of Shamroth sign, and use it to evaluate for clubbing. Shamroth sign is the loss of the diamond that is created by placing the back surfaces of opposite terminal phalanges together.
I have found that it’s easier to diagnose mild clubbing by looking at the finger in profile. If the ratio of the distal phalangeal depth compared to the depth across the distal interphalangeal joint is greater than 1:1, then clubbing is present.3
Pearls
1. Have the patient try yawning to better see the pharynx without using a tongue blade.
2. Try the technique of auscultatory percussion to be more accurate at picking up pleural effusions.
3. Know your hematocrit, so you can better use color shade to assess for anemia.
4. Try looking at fingers in profile to pick up clubbing.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Guarino JR and Guarino JC. Auscultatory percussion: A simple method to detect pleural effusion. J Gen Intern Med. 1994 Feb;9(2):71-4.
2. Strobach RS et al. The value of the physical examination in the diagnosis of anemia. Correlation of the physical findings and the hemoglobin concentration. Arch Intern Med. 1988 Apr;148(4):831-2.
3. Spicknall KE et al. Clubbing: an update on diagnosis, differential diagnosis, pathophysiology, and clinical relevance. J Am Acad Dermatol. 2005 Jun;52(6):1020-8.
I would like to start the new year off by returning to the past – when the physical exam was emphasized and utilized in decision making. I think a big reason that its use has diminished in recent years is due to the physical exam not having been emphasized in training.
For those seeking to increase their comfort with conducting the physical exam, below are several methods I have found helpful to use in practice.
Examining the pharynx
We were usually taught to ask the patient to say ahhh, with or without a nasty tongue depressor.
When I was on my pediatrics rotation, I was taught to ask the patients to roar like a lion, which always gave a nice look at their posterior pharynx. The kids also really liked doing this, but it might seem a little strange to ask adults to do this.
A technique I have found that works well with adults is to ask them to yawn. I have found that this get me a great look at the pharynx for about half of my patients.
Auscultatory percussion for pleural effusions
Guarino and colleagues described a technique that is easily mastered and very effective for determining the presence of pleural effusions.1 It involves placing the stethoscope 3 cm below the last rib in the mid clavicular line and tapping from the apex down to the last rib.
For patients without effusion, a sharp change to a loud percussion note will occur at the last rib.
If the patient has an effusion, the loud percussion note will start at the top of the effusion.
This method was remarkably successful at finding pleural effusions. In the study, Dr. Guarino found a sensitivity of 96% and a specificity of 100%.
Physical exam for anemia
Look at the nails and see if they look pale. How can we do this?
The first step is to know what your own hematocrit is. You can then compare the color of your nail to that of the patient.
If you have a normal hematocrit and the patient’s nail bed color is lighter than yours, the patient likely has anemia. If you do this frequently, you will get good at estimating hematocrit. This is especially important if you do not have labs readily available.
Another way to assess for anemia is to look at the color tint of the lower conjunctiva. The best way to look for this is to look at whether there is a generous amount of visible capillaries in the lower conjunctiva. Patients without anemia have a darker red color because of these vessels, whereas patients with anemia are a lighter pink.
Strobach and colleagues2 looked at both nail bed rubor and color tint of the lower conjunctiva and found that both reliably predicted presence and degree of anemia.
Determining if clubbing is present
Most physicians are aware of Shamroth sign, and use it to evaluate for clubbing. Shamroth sign is the loss of the diamond that is created by placing the back surfaces of opposite terminal phalanges together.
I have found that it’s easier to diagnose mild clubbing by looking at the finger in profile. If the ratio of the distal phalangeal depth compared to the depth across the distal interphalangeal joint is greater than 1:1, then clubbing is present.3
Pearls
1. Have the patient try yawning to better see the pharynx without using a tongue blade.
2. Try the technique of auscultatory percussion to be more accurate at picking up pleural effusions.
3. Know your hematocrit, so you can better use color shade to assess for anemia.
4. Try looking at fingers in profile to pick up clubbing.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Guarino JR and Guarino JC. Auscultatory percussion: A simple method to detect pleural effusion. J Gen Intern Med. 1994 Feb;9(2):71-4.
2. Strobach RS et al. The value of the physical examination in the diagnosis of anemia. Correlation of the physical findings and the hemoglobin concentration. Arch Intern Med. 1988 Apr;148(4):831-2.
3. Spicknall KE et al. Clubbing: an update on diagnosis, differential diagnosis, pathophysiology, and clinical relevance. J Am Acad Dermatol. 2005 Jun;52(6):1020-8.
I would like to start the new year off by returning to the past – when the physical exam was emphasized and utilized in decision making. I think a big reason that its use has diminished in recent years is due to the physical exam not having been emphasized in training.
For those seeking to increase their comfort with conducting the physical exam, below are several methods I have found helpful to use in practice.
Examining the pharynx
We were usually taught to ask the patient to say ahhh, with or without a nasty tongue depressor.
When I was on my pediatrics rotation, I was taught to ask the patients to roar like a lion, which always gave a nice look at their posterior pharynx. The kids also really liked doing this, but it might seem a little strange to ask adults to do this.
A technique I have found that works well with adults is to ask them to yawn. I have found that this get me a great look at the pharynx for about half of my patients.
Auscultatory percussion for pleural effusions
Guarino and colleagues described a technique that is easily mastered and very effective for determining the presence of pleural effusions.1 It involves placing the stethoscope 3 cm below the last rib in the mid clavicular line and tapping from the apex down to the last rib.
For patients without effusion, a sharp change to a loud percussion note will occur at the last rib.
If the patient has an effusion, the loud percussion note will start at the top of the effusion.
This method was remarkably successful at finding pleural effusions. In the study, Dr. Guarino found a sensitivity of 96% and a specificity of 100%.
Physical exam for anemia
Look at the nails and see if they look pale. How can we do this?
The first step is to know what your own hematocrit is. You can then compare the color of your nail to that of the patient.
If you have a normal hematocrit and the patient’s nail bed color is lighter than yours, the patient likely has anemia. If you do this frequently, you will get good at estimating hematocrit. This is especially important if you do not have labs readily available.
Another way to assess for anemia is to look at the color tint of the lower conjunctiva. The best way to look for this is to look at whether there is a generous amount of visible capillaries in the lower conjunctiva. Patients without anemia have a darker red color because of these vessels, whereas patients with anemia are a lighter pink.
Strobach and colleagues2 looked at both nail bed rubor and color tint of the lower conjunctiva and found that both reliably predicted presence and degree of anemia.
Determining if clubbing is present
Most physicians are aware of Shamroth sign, and use it to evaluate for clubbing. Shamroth sign is the loss of the diamond that is created by placing the back surfaces of opposite terminal phalanges together.
I have found that it’s easier to diagnose mild clubbing by looking at the finger in profile. If the ratio of the distal phalangeal depth compared to the depth across the distal interphalangeal joint is greater than 1:1, then clubbing is present.3
Pearls
1. Have the patient try yawning to better see the pharynx without using a tongue blade.
2. Try the technique of auscultatory percussion to be more accurate at picking up pleural effusions.
3. Know your hematocrit, so you can better use color shade to assess for anemia.
4. Try looking at fingers in profile to pick up clubbing.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Guarino JR and Guarino JC. Auscultatory percussion: A simple method to detect pleural effusion. J Gen Intern Med. 1994 Feb;9(2):71-4.
2. Strobach RS et al. The value of the physical examination in the diagnosis of anemia. Correlation of the physical findings and the hemoglobin concentration. Arch Intern Med. 1988 Apr;148(4):831-2.
3. Spicknall KE et al. Clubbing: an update on diagnosis, differential diagnosis, pathophysiology, and clinical relevance. J Am Acad Dermatol. 2005 Jun;52(6):1020-8.
‘No one’s talking about it’: Infertility and one specialty’s onerous board exams
It would be impossible for her to fly the 2,500 miles from New York to the test site in Tucson, Ariz., when she could go into labor at any moment. She asked the American Board of Radiology – which oversees the process – if she could take the oral exam on Zoom or shift the timing a few weeks earlier or later.
The response: If she decided not to sit for the exam in person on the date specified, she would have to wait an entire year for the next test.
“I felt: Angry. Sad. Helpless. Inconsequential,” Dr. Dover tweeted. “But I will not be silent.”
The experience motivated Dr. Dover and six colleagues to conduct a study about how radiation oncology’s onerous four-exam board certification process has disproportionately burdened women.
The study, published online in Practical Radiation Oncology on Nov. 3, 2021, revealed that almost 60% of the early-career female radiation oncologists surveyed had delayed or were timing their pregnancies to accommodate their board exams. Women who chose to delay pregnancy were 2.5 times more likely to experience infertility.
“When we started doing the study, we didn’t realize just how common it was for people to wrap so much of their [family planning decisions] around taking these board exams,” said study coauthor Adrianna Henson Masters, MD, a radiation oncologist at Springfield (Ill.) Clinic. “How crazy is that? And no one’s talking about it.”
However, once the study appeared online, physicians took to Twitter to comment on the challenges of the board certification process, while others demanded change. One radiation oncologist even shared her decision not to have a child until she passed her board exams.
The study also got the attention of the American Board of Radiology, which governs certification for the specialty. In a response, leaders of the organization agreed that “the issues raised are significant and worthy of thoughtful consideration” and highlighted how, in light of the COVID-19 pandemic, the board has provided greater flexibility to the exam process – transitioning to remote testing and offering two dates for each exam in 2021.
But will the changes last? And will they help reduce the burden these exams place on families and family planning?
Inside board certification before the pandemic
While other specialties require one or two exams for board certification, radiation oncology is the only medical field that requires candidates pass four exams – three qualifying written tests, followed by a certifying oral exam. Since 2004, these exams, which cover physics, radiation biology, and clinical radiation oncology, have taken place over 3 years at specific locations across the country.
Radiation oncology residents have reported spending hundreds of hours preparing for each of these high-stakes evaluations. Fail or miss one and an already time-consuming process draws out, with major repercussions for career advancement and earnings.
“Passing and achieving board certification is the capstone of medical specialty training and, for many, is a prerequisite for attaining partnership or a promotion,” said study coauthor Chelain Goodman, MD, PhD, a radiation oncologist at the University of Texas MD Anderson Cancer Center, Houston.
To top it off, this process may be contributing to the gender disparity in radiation oncology, the study suggests. Only 25%-30% of practicing radiation oncologists are women, making it one of the lowest-ranking specialties when it comes to female representation.
“I think [this exam process] creates some disincentive when female medical students see that these are issues that early-career radiation oncologists are facing,” said Dr. Dover, who practices at Memorial Sloan Kettering Cancer Center, New York. “[Students may instead] choose a specialty that they believe will be more supportive of them and their family planning goals. That’s definitely a big concern for a field that wants to attract the top candidates.”
For those who do pick radiation oncology, the system of board exams often requires prospective parents to choose among three options: Try to time delivery before or between exams, put off pregnancy or adoption until exams are done, or delay board certification.
A balancing act: Board exams and family planning
Like Dr. Dover, Dr. Masters opted for door No. 1. She tried to time the birth of her daughter to fall several months before her first board exam.
She hoped her careful planning would reduce the stress of both major life events. But that was not the case. At 35 weeks, Dr. Masters found herself in the hospital with preeclampsia and symptomatic hypertension.
While receiving a magnesium sulfate drip to prevent a seizure, she frantically typed her patient list before her vision got too blurry to see the screen.
“That is ridiculous,” Dr. Masters said. “But so is a system that makes this the expectation [for pregnant physicians].”
During her hospital stay, Dr. Masters was induced. She suspects the stress of prepping for the board exam coupled with being pregnant and continuing to work long hours as a resident contributed to her pregnancy complications.
This juggling act can bleed into exam day as well. When interviewing women for their study, Dr. Masters and colleagues uncovered personal accounts of the challenges pregnant women and new mothers faced during their exams.
One woman described being granted lactation accommodation ahead of time, but when she arrived for her first two written exams, the testing center had no record of her request. She ended up breast-pumping in a coat closet next to the cleaning supplies while her male coresidents ate lunch and reviewed their notes.
“I started my physics exam in tears, completely anxious,” she reported. “I didn’t get to eat lunch. I was physically uncomfortable and emotionally wiped during both exams.”
Another woman had contractions during her written clinical boards, but “thankfully” passed her exam and gave birth 2 days later.
“It might sound crazy that we would put ourselves through things like that just to take an exam,” Dr. Dover said. “But because it does have the potential to sharply shape our early professional trajectory, we push through it. Otherwise, we’re going to be left behind by our male peers.”
This pressure to push through can be intense.
Still recovering from a difficult pregnancy, Dr. Masters returned to work when her daughter was just 5 weeks old. Although not ready to return to work, she felt too scared to ask for more time off after seeing other new mothers receive negative comments about not working hard enough.
Enter door No. 2: The pregnancy and postpregnancy experiences were so traumatizing that she decided to put off trying for a second child until after her exams.
Now board certified and 38 years old, Dr. Masters is worried she won’t be able to conceive as easily as before.
“So, we’re stuck in limbo, starting the process again and being nervous about it because what if it’s not so easy at this age?” she said. “And what if it could have been easy, in different circumstances, with a different specialty?”
Dr. Masters’ concerns are justified. Of the 126 women interviewed for the study, those who delayed pregnancy because of the board exams were significantly more likely to have fertility problems (46% vs. 18%), and 20% reported experiencing infertility.
This finding dovetails with previous research showing that almost 25% of female physicians who attempt to become pregnant are diagnosed with infertility – nearly twice the rate of the general population. This high rate of infertility has been attributed to professional pressures and stress, long hours on the job, and delaying pregnancy during medical training.
But choosing door No. 3 – focusing on family over exams – has downsides as well. Board certification is a prerequisite for almost every partnership position or promotion track within academic medicine and delaying certification can significantly hinder a physician’s career and finances.
Radiation oncologists who aren’t certified often remain in salaried positions until they can make partnership and earn a portion of the practice’s profits, “which could easily change your annual compensation by six digits,” Dr. Dover said.
According to the team’s study, annual compensation typically increases by $30,000-$50,000 after board certification, with some reporting an increase of over $100,000. That salary hike also impacts physicians’ ability to pay off medical school loans, make financial investments, and afford the cost of childcare.
In other words, when it comes to family planning, there’s often no good option.
Change on the horizon
When the pandemic struck, the American Board of Radiology quickly went into triage mode, postponing in-person board certification exams scheduled in 2020 and brainstorming solutions.
By June, the organization announced that the exams would switch to a virtual format in 2021. Each test would be offered twice – once early in the year for candidates like Dover whose postponed 2020 exams had ultimately been canceled, and then again for those already planning to take their tests in 2021.
The shift to remote testing was a boon. Taking the tests from home not only allowed candidates to forgo the cost, stress, and time of travel, it also mitigated the burden of juggling pregnancy and parenting needs.
For example, Courtney Hentz, MD, a pediatric radiation oncologist at Loyola University Chicago, Maywood, Ill., and a study coauthor, was given the choice to take a virtual exam in one day with two breastfeeding breaks or to spread the exam over 2 days with one breastfeeding break each day.
“Transitioning exams to a virtual format has been a really big achievement that the American Board of Radiology should be applauded for,” Dr. Dover said.
Not only that, offering the exams multiple times a year has “significantly increased flexibility for candidates as they juggle completing residency, starting at their first practice, and balancing time with their family,” Dr. Goodman added.
Brent Wagner, MD, MBA, executive director of the American Board of Radiology, Tucson, Ariz., said in an interviewthat remote exams are here to stay. “I don’t foresee us ever going back to in-person board exams,” said Dr. Wagner, a diagnostic radiologist. “Administering exams remotely last year worked better than I could have expected.”
Dr. Wagner said the American Board of Radiology also plans to keep two dates for the oral certifying exam for the foreseeable future, though will revert to one date for the written qualifying exams.
“In a perfect world, we’d offer an exam every quarter,” he said. However, providing multiple dates for the written exams “is not practical with a cohort of a few hundred people,” given the staff resources needed to create and score twice the number of items each year. The board did not rule out reassessing this decision in the future, “as examination development software improves and more resources become available.”
Another big change, proposed by Dr. Dover, Dr. Goodman, and others, would be to combine the four exams into fewer tests, such as consolidating the three written exams into one. Such a shift would allow physicians to launch their careers sooner and begin focusing on other career-advancing endeavors such as research and publishing. It would also significantly improve radiation oncologists’ quality of life.
“The amount of time that you spend studying for these very high-level, high-stakes exams really puts a toll on your mental health,” Dr. Dover said. “The longer it’s dragged out, the longer you’re dealing with that, and it contributes tremendously to poor job satisfaction and work-life balance.”
The American Board of Radiology said it is discussing options for consolidating the exams, but the challenge with combining the three written exams into one comes down to scoring. “We need to get a statistically valid result in all three categories,” Dr. Wagner said.
Another recent change: The American Board of Radiology is now allowing residents flexibility on the sequence of the written exams.
“In the past, we said you had to pass the physics exam before moving on to clinical radiology, but now we’re letting residents decide the order for themselves,” Dr. Wagner said. “This change may introduce more flexibility for someone who missed their first opportunity to take the physics exam but is ready to take the clinical exam.”
Dr. Wagner added: “We’re learning as we go, and I tell our staff that there’s no reason we should think we’re done making improvements. It’s going to keep getting better.”
The recent changes have already made a difference to radiation oncologists. And many hope to build on this new foundation to move the specialty toward a more family-friendly, equitable culture.
“I think as people in a caregiver profession, it’s hard to prioritize doing things for yourself or your own family sometimes; it’s hard to speak up and say: ‘We need something different,’ ” Dr. Masters said. “I think we have [an opportunity] to capitalize on the momentum we have now.”
A version of this article first appeared on Medscape.com.
It would be impossible for her to fly the 2,500 miles from New York to the test site in Tucson, Ariz., when she could go into labor at any moment. She asked the American Board of Radiology – which oversees the process – if she could take the oral exam on Zoom or shift the timing a few weeks earlier or later.
The response: If she decided not to sit for the exam in person on the date specified, she would have to wait an entire year for the next test.
“I felt: Angry. Sad. Helpless. Inconsequential,” Dr. Dover tweeted. “But I will not be silent.”
The experience motivated Dr. Dover and six colleagues to conduct a study about how radiation oncology’s onerous four-exam board certification process has disproportionately burdened women.
The study, published online in Practical Radiation Oncology on Nov. 3, 2021, revealed that almost 60% of the early-career female radiation oncologists surveyed had delayed or were timing their pregnancies to accommodate their board exams. Women who chose to delay pregnancy were 2.5 times more likely to experience infertility.
“When we started doing the study, we didn’t realize just how common it was for people to wrap so much of their [family planning decisions] around taking these board exams,” said study coauthor Adrianna Henson Masters, MD, a radiation oncologist at Springfield (Ill.) Clinic. “How crazy is that? And no one’s talking about it.”
However, once the study appeared online, physicians took to Twitter to comment on the challenges of the board certification process, while others demanded change. One radiation oncologist even shared her decision not to have a child until she passed her board exams.
The study also got the attention of the American Board of Radiology, which governs certification for the specialty. In a response, leaders of the organization agreed that “the issues raised are significant and worthy of thoughtful consideration” and highlighted how, in light of the COVID-19 pandemic, the board has provided greater flexibility to the exam process – transitioning to remote testing and offering two dates for each exam in 2021.
But will the changes last? And will they help reduce the burden these exams place on families and family planning?
Inside board certification before the pandemic
While other specialties require one or two exams for board certification, radiation oncology is the only medical field that requires candidates pass four exams – three qualifying written tests, followed by a certifying oral exam. Since 2004, these exams, which cover physics, radiation biology, and clinical radiation oncology, have taken place over 3 years at specific locations across the country.
Radiation oncology residents have reported spending hundreds of hours preparing for each of these high-stakes evaluations. Fail or miss one and an already time-consuming process draws out, with major repercussions for career advancement and earnings.
“Passing and achieving board certification is the capstone of medical specialty training and, for many, is a prerequisite for attaining partnership or a promotion,” said study coauthor Chelain Goodman, MD, PhD, a radiation oncologist at the University of Texas MD Anderson Cancer Center, Houston.
To top it off, this process may be contributing to the gender disparity in radiation oncology, the study suggests. Only 25%-30% of practicing radiation oncologists are women, making it one of the lowest-ranking specialties when it comes to female representation.
“I think [this exam process] creates some disincentive when female medical students see that these are issues that early-career radiation oncologists are facing,” said Dr. Dover, who practices at Memorial Sloan Kettering Cancer Center, New York. “[Students may instead] choose a specialty that they believe will be more supportive of them and their family planning goals. That’s definitely a big concern for a field that wants to attract the top candidates.”
For those who do pick radiation oncology, the system of board exams often requires prospective parents to choose among three options: Try to time delivery before or between exams, put off pregnancy or adoption until exams are done, or delay board certification.
A balancing act: Board exams and family planning
Like Dr. Dover, Dr. Masters opted for door No. 1. She tried to time the birth of her daughter to fall several months before her first board exam.
She hoped her careful planning would reduce the stress of both major life events. But that was not the case. At 35 weeks, Dr. Masters found herself in the hospital with preeclampsia and symptomatic hypertension.
While receiving a magnesium sulfate drip to prevent a seizure, she frantically typed her patient list before her vision got too blurry to see the screen.
“That is ridiculous,” Dr. Masters said. “But so is a system that makes this the expectation [for pregnant physicians].”
During her hospital stay, Dr. Masters was induced. She suspects the stress of prepping for the board exam coupled with being pregnant and continuing to work long hours as a resident contributed to her pregnancy complications.
This juggling act can bleed into exam day as well. When interviewing women for their study, Dr. Masters and colleagues uncovered personal accounts of the challenges pregnant women and new mothers faced during their exams.
One woman described being granted lactation accommodation ahead of time, but when she arrived for her first two written exams, the testing center had no record of her request. She ended up breast-pumping in a coat closet next to the cleaning supplies while her male coresidents ate lunch and reviewed their notes.
“I started my physics exam in tears, completely anxious,” she reported. “I didn’t get to eat lunch. I was physically uncomfortable and emotionally wiped during both exams.”
Another woman had contractions during her written clinical boards, but “thankfully” passed her exam and gave birth 2 days later.
“It might sound crazy that we would put ourselves through things like that just to take an exam,” Dr. Dover said. “But because it does have the potential to sharply shape our early professional trajectory, we push through it. Otherwise, we’re going to be left behind by our male peers.”
This pressure to push through can be intense.
Still recovering from a difficult pregnancy, Dr. Masters returned to work when her daughter was just 5 weeks old. Although not ready to return to work, she felt too scared to ask for more time off after seeing other new mothers receive negative comments about not working hard enough.
Enter door No. 2: The pregnancy and postpregnancy experiences were so traumatizing that she decided to put off trying for a second child until after her exams.
Now board certified and 38 years old, Dr. Masters is worried she won’t be able to conceive as easily as before.
“So, we’re stuck in limbo, starting the process again and being nervous about it because what if it’s not so easy at this age?” she said. “And what if it could have been easy, in different circumstances, with a different specialty?”
Dr. Masters’ concerns are justified. Of the 126 women interviewed for the study, those who delayed pregnancy because of the board exams were significantly more likely to have fertility problems (46% vs. 18%), and 20% reported experiencing infertility.
This finding dovetails with previous research showing that almost 25% of female physicians who attempt to become pregnant are diagnosed with infertility – nearly twice the rate of the general population. This high rate of infertility has been attributed to professional pressures and stress, long hours on the job, and delaying pregnancy during medical training.
But choosing door No. 3 – focusing on family over exams – has downsides as well. Board certification is a prerequisite for almost every partnership position or promotion track within academic medicine and delaying certification can significantly hinder a physician’s career and finances.
Radiation oncologists who aren’t certified often remain in salaried positions until they can make partnership and earn a portion of the practice’s profits, “which could easily change your annual compensation by six digits,” Dr. Dover said.
According to the team’s study, annual compensation typically increases by $30,000-$50,000 after board certification, with some reporting an increase of over $100,000. That salary hike also impacts physicians’ ability to pay off medical school loans, make financial investments, and afford the cost of childcare.
In other words, when it comes to family planning, there’s often no good option.
Change on the horizon
When the pandemic struck, the American Board of Radiology quickly went into triage mode, postponing in-person board certification exams scheduled in 2020 and brainstorming solutions.
By June, the organization announced that the exams would switch to a virtual format in 2021. Each test would be offered twice – once early in the year for candidates like Dover whose postponed 2020 exams had ultimately been canceled, and then again for those already planning to take their tests in 2021.
The shift to remote testing was a boon. Taking the tests from home not only allowed candidates to forgo the cost, stress, and time of travel, it also mitigated the burden of juggling pregnancy and parenting needs.
For example, Courtney Hentz, MD, a pediatric radiation oncologist at Loyola University Chicago, Maywood, Ill., and a study coauthor, was given the choice to take a virtual exam in one day with two breastfeeding breaks or to spread the exam over 2 days with one breastfeeding break each day.
“Transitioning exams to a virtual format has been a really big achievement that the American Board of Radiology should be applauded for,” Dr. Dover said.
Not only that, offering the exams multiple times a year has “significantly increased flexibility for candidates as they juggle completing residency, starting at their first practice, and balancing time with their family,” Dr. Goodman added.
Brent Wagner, MD, MBA, executive director of the American Board of Radiology, Tucson, Ariz., said in an interviewthat remote exams are here to stay. “I don’t foresee us ever going back to in-person board exams,” said Dr. Wagner, a diagnostic radiologist. “Administering exams remotely last year worked better than I could have expected.”
Dr. Wagner said the American Board of Radiology also plans to keep two dates for the oral certifying exam for the foreseeable future, though will revert to one date for the written qualifying exams.
“In a perfect world, we’d offer an exam every quarter,” he said. However, providing multiple dates for the written exams “is not practical with a cohort of a few hundred people,” given the staff resources needed to create and score twice the number of items each year. The board did not rule out reassessing this decision in the future, “as examination development software improves and more resources become available.”
Another big change, proposed by Dr. Dover, Dr. Goodman, and others, would be to combine the four exams into fewer tests, such as consolidating the three written exams into one. Such a shift would allow physicians to launch their careers sooner and begin focusing on other career-advancing endeavors such as research and publishing. It would also significantly improve radiation oncologists’ quality of life.
“The amount of time that you spend studying for these very high-level, high-stakes exams really puts a toll on your mental health,” Dr. Dover said. “The longer it’s dragged out, the longer you’re dealing with that, and it contributes tremendously to poor job satisfaction and work-life balance.”
The American Board of Radiology said it is discussing options for consolidating the exams, but the challenge with combining the three written exams into one comes down to scoring. “We need to get a statistically valid result in all three categories,” Dr. Wagner said.
Another recent change: The American Board of Radiology is now allowing residents flexibility on the sequence of the written exams.
“In the past, we said you had to pass the physics exam before moving on to clinical radiology, but now we’re letting residents decide the order for themselves,” Dr. Wagner said. “This change may introduce more flexibility for someone who missed their first opportunity to take the physics exam but is ready to take the clinical exam.”
Dr. Wagner added: “We’re learning as we go, and I tell our staff that there’s no reason we should think we’re done making improvements. It’s going to keep getting better.”
The recent changes have already made a difference to radiation oncologists. And many hope to build on this new foundation to move the specialty toward a more family-friendly, equitable culture.
“I think as people in a caregiver profession, it’s hard to prioritize doing things for yourself or your own family sometimes; it’s hard to speak up and say: ‘We need something different,’ ” Dr. Masters said. “I think we have [an opportunity] to capitalize on the momentum we have now.”
A version of this article first appeared on Medscape.com.
It would be impossible for her to fly the 2,500 miles from New York to the test site in Tucson, Ariz., when she could go into labor at any moment. She asked the American Board of Radiology – which oversees the process – if she could take the oral exam on Zoom or shift the timing a few weeks earlier or later.
The response: If she decided not to sit for the exam in person on the date specified, she would have to wait an entire year for the next test.
“I felt: Angry. Sad. Helpless. Inconsequential,” Dr. Dover tweeted. “But I will not be silent.”
The experience motivated Dr. Dover and six colleagues to conduct a study about how radiation oncology’s onerous four-exam board certification process has disproportionately burdened women.
The study, published online in Practical Radiation Oncology on Nov. 3, 2021, revealed that almost 60% of the early-career female radiation oncologists surveyed had delayed or were timing their pregnancies to accommodate their board exams. Women who chose to delay pregnancy were 2.5 times more likely to experience infertility.
“When we started doing the study, we didn’t realize just how common it was for people to wrap so much of their [family planning decisions] around taking these board exams,” said study coauthor Adrianna Henson Masters, MD, a radiation oncologist at Springfield (Ill.) Clinic. “How crazy is that? And no one’s talking about it.”
However, once the study appeared online, physicians took to Twitter to comment on the challenges of the board certification process, while others demanded change. One radiation oncologist even shared her decision not to have a child until she passed her board exams.
The study also got the attention of the American Board of Radiology, which governs certification for the specialty. In a response, leaders of the organization agreed that “the issues raised are significant and worthy of thoughtful consideration” and highlighted how, in light of the COVID-19 pandemic, the board has provided greater flexibility to the exam process – transitioning to remote testing and offering two dates for each exam in 2021.
But will the changes last? And will they help reduce the burden these exams place on families and family planning?
Inside board certification before the pandemic
While other specialties require one or two exams for board certification, radiation oncology is the only medical field that requires candidates pass four exams – three qualifying written tests, followed by a certifying oral exam. Since 2004, these exams, which cover physics, radiation biology, and clinical radiation oncology, have taken place over 3 years at specific locations across the country.
Radiation oncology residents have reported spending hundreds of hours preparing for each of these high-stakes evaluations. Fail or miss one and an already time-consuming process draws out, with major repercussions for career advancement and earnings.
“Passing and achieving board certification is the capstone of medical specialty training and, for many, is a prerequisite for attaining partnership or a promotion,” said study coauthor Chelain Goodman, MD, PhD, a radiation oncologist at the University of Texas MD Anderson Cancer Center, Houston.
To top it off, this process may be contributing to the gender disparity in radiation oncology, the study suggests. Only 25%-30% of practicing radiation oncologists are women, making it one of the lowest-ranking specialties when it comes to female representation.
“I think [this exam process] creates some disincentive when female medical students see that these are issues that early-career radiation oncologists are facing,” said Dr. Dover, who practices at Memorial Sloan Kettering Cancer Center, New York. “[Students may instead] choose a specialty that they believe will be more supportive of them and their family planning goals. That’s definitely a big concern for a field that wants to attract the top candidates.”
For those who do pick radiation oncology, the system of board exams often requires prospective parents to choose among three options: Try to time delivery before or between exams, put off pregnancy or adoption until exams are done, or delay board certification.
A balancing act: Board exams and family planning
Like Dr. Dover, Dr. Masters opted for door No. 1. She tried to time the birth of her daughter to fall several months before her first board exam.
She hoped her careful planning would reduce the stress of both major life events. But that was not the case. At 35 weeks, Dr. Masters found herself in the hospital with preeclampsia and symptomatic hypertension.
While receiving a magnesium sulfate drip to prevent a seizure, she frantically typed her patient list before her vision got too blurry to see the screen.
“That is ridiculous,” Dr. Masters said. “But so is a system that makes this the expectation [for pregnant physicians].”
During her hospital stay, Dr. Masters was induced. She suspects the stress of prepping for the board exam coupled with being pregnant and continuing to work long hours as a resident contributed to her pregnancy complications.
This juggling act can bleed into exam day as well. When interviewing women for their study, Dr. Masters and colleagues uncovered personal accounts of the challenges pregnant women and new mothers faced during their exams.
One woman described being granted lactation accommodation ahead of time, but when she arrived for her first two written exams, the testing center had no record of her request. She ended up breast-pumping in a coat closet next to the cleaning supplies while her male coresidents ate lunch and reviewed their notes.
“I started my physics exam in tears, completely anxious,” she reported. “I didn’t get to eat lunch. I was physically uncomfortable and emotionally wiped during both exams.”
Another woman had contractions during her written clinical boards, but “thankfully” passed her exam and gave birth 2 days later.
“It might sound crazy that we would put ourselves through things like that just to take an exam,” Dr. Dover said. “But because it does have the potential to sharply shape our early professional trajectory, we push through it. Otherwise, we’re going to be left behind by our male peers.”
This pressure to push through can be intense.
Still recovering from a difficult pregnancy, Dr. Masters returned to work when her daughter was just 5 weeks old. Although not ready to return to work, she felt too scared to ask for more time off after seeing other new mothers receive negative comments about not working hard enough.
Enter door No. 2: The pregnancy and postpregnancy experiences were so traumatizing that she decided to put off trying for a second child until after her exams.
Now board certified and 38 years old, Dr. Masters is worried she won’t be able to conceive as easily as before.
“So, we’re stuck in limbo, starting the process again and being nervous about it because what if it’s not so easy at this age?” she said. “And what if it could have been easy, in different circumstances, with a different specialty?”
Dr. Masters’ concerns are justified. Of the 126 women interviewed for the study, those who delayed pregnancy because of the board exams were significantly more likely to have fertility problems (46% vs. 18%), and 20% reported experiencing infertility.
This finding dovetails with previous research showing that almost 25% of female physicians who attempt to become pregnant are diagnosed with infertility – nearly twice the rate of the general population. This high rate of infertility has been attributed to professional pressures and stress, long hours on the job, and delaying pregnancy during medical training.
But choosing door No. 3 – focusing on family over exams – has downsides as well. Board certification is a prerequisite for almost every partnership position or promotion track within academic medicine and delaying certification can significantly hinder a physician’s career and finances.
Radiation oncologists who aren’t certified often remain in salaried positions until they can make partnership and earn a portion of the practice’s profits, “which could easily change your annual compensation by six digits,” Dr. Dover said.
According to the team’s study, annual compensation typically increases by $30,000-$50,000 after board certification, with some reporting an increase of over $100,000. That salary hike also impacts physicians’ ability to pay off medical school loans, make financial investments, and afford the cost of childcare.
In other words, when it comes to family planning, there’s often no good option.
Change on the horizon
When the pandemic struck, the American Board of Radiology quickly went into triage mode, postponing in-person board certification exams scheduled in 2020 and brainstorming solutions.
By June, the organization announced that the exams would switch to a virtual format in 2021. Each test would be offered twice – once early in the year for candidates like Dover whose postponed 2020 exams had ultimately been canceled, and then again for those already planning to take their tests in 2021.
The shift to remote testing was a boon. Taking the tests from home not only allowed candidates to forgo the cost, stress, and time of travel, it also mitigated the burden of juggling pregnancy and parenting needs.
For example, Courtney Hentz, MD, a pediatric radiation oncologist at Loyola University Chicago, Maywood, Ill., and a study coauthor, was given the choice to take a virtual exam in one day with two breastfeeding breaks or to spread the exam over 2 days with one breastfeeding break each day.
“Transitioning exams to a virtual format has been a really big achievement that the American Board of Radiology should be applauded for,” Dr. Dover said.
Not only that, offering the exams multiple times a year has “significantly increased flexibility for candidates as they juggle completing residency, starting at their first practice, and balancing time with their family,” Dr. Goodman added.
Brent Wagner, MD, MBA, executive director of the American Board of Radiology, Tucson, Ariz., said in an interviewthat remote exams are here to stay. “I don’t foresee us ever going back to in-person board exams,” said Dr. Wagner, a diagnostic radiologist. “Administering exams remotely last year worked better than I could have expected.”
Dr. Wagner said the American Board of Radiology also plans to keep two dates for the oral certifying exam for the foreseeable future, though will revert to one date for the written qualifying exams.
“In a perfect world, we’d offer an exam every quarter,” he said. However, providing multiple dates for the written exams “is not practical with a cohort of a few hundred people,” given the staff resources needed to create and score twice the number of items each year. The board did not rule out reassessing this decision in the future, “as examination development software improves and more resources become available.”
Another big change, proposed by Dr. Dover, Dr. Goodman, and others, would be to combine the four exams into fewer tests, such as consolidating the three written exams into one. Such a shift would allow physicians to launch their careers sooner and begin focusing on other career-advancing endeavors such as research and publishing. It would also significantly improve radiation oncologists’ quality of life.
“The amount of time that you spend studying for these very high-level, high-stakes exams really puts a toll on your mental health,” Dr. Dover said. “The longer it’s dragged out, the longer you’re dealing with that, and it contributes tremendously to poor job satisfaction and work-life balance.”
The American Board of Radiology said it is discussing options for consolidating the exams, but the challenge with combining the three written exams into one comes down to scoring. “We need to get a statistically valid result in all three categories,” Dr. Wagner said.
Another recent change: The American Board of Radiology is now allowing residents flexibility on the sequence of the written exams.
“In the past, we said you had to pass the physics exam before moving on to clinical radiology, but now we’re letting residents decide the order for themselves,” Dr. Wagner said. “This change may introduce more flexibility for someone who missed their first opportunity to take the physics exam but is ready to take the clinical exam.”
Dr. Wagner added: “We’re learning as we go, and I tell our staff that there’s no reason we should think we’re done making improvements. It’s going to keep getting better.”
The recent changes have already made a difference to radiation oncologists. And many hope to build on this new foundation to move the specialty toward a more family-friendly, equitable culture.
“I think as people in a caregiver profession, it’s hard to prioritize doing things for yourself or your own family sometimes; it’s hard to speak up and say: ‘We need something different,’ ” Dr. Masters said. “I think we have [an opportunity] to capitalize on the momentum we have now.”
A version of this article first appeared on Medscape.com.
Study finds sharp drop in opioid scripts among most specialties
The volume of prescription opioids dispensed at retail pharmacies in the United States dropped by 21% in recent years amid efforts to reduce unnecessary use of the painkillers, but the rate of decline varied greatly among types of patients and by type of clinician, a study found.
In a brief report published by Annals of Internal Medicine, researchers from the nonprofit RAND Corp reported an analysis of opioid prescriptions from two periods, 2008-2009 and 2017-2018.
The researchers sought to assess total opioid use rather than simply track the number of pills dispensed. So they used days’ supply and total daily dose to calculate per capita morphine milligram equivalents (MME) for opioid prescriptions, write Bradley D. Stein, MD, PhD, MPH, the study’s lead author and a senior physician researcher at RAND Corp, and his coauthors in their paper.
For the study, the researchers used data from the consulting firm IQVIA, which they say covers about 90% of U.S. prescriptions. Total opioid volume per capita by prescriptions filled in retail pharmacies decreased from 951.4 MME in 2008-2009 to 749.3 MME in 2017-2018, Dr. Stein’s group found.
(In 2020, IQVIA separately said that prescription opioid use per adult in this country rose from an average of 16 pills, or 134 MMEs, in 1992 to a peak of about 55 pills a person, or 790 MMEs, in 2011. By 2019, opioid use per adult had declined to 29 pills and 366 MMEs per capita.)
The RAND report found substantial variation in opioid volume by type of insurance, including a 41.5% decline (636.5 MME to 372.6 MME) among people covered by commercial health plans. That exceeded the 27.7% drop seen for people enrolled in Medicaid (646.8 MME to 467.7 MME). The decline was smaller (17.5%; 2,780.2 MME to 2,294.2 MME) for those on Medicare, who as a group used the most opioids.
‘Almost functions as a Rorschach test’
The causes of the decline are easy to guess, although definitive conclusions are impossible, Dr. Stein told this news organization.
Significant work has been done in recent years to change attitudes about opioid prescriptions by physicians, researchers, and lawmakers. Aggressive promotion of prescription painkillers, particularly Purdue Pharma’s OxyContin, in the 1990s, is widely cited as the triggering event for the national opioid crisis.
In response, states created databases known as prescription drug monitoring programs. The Centers for Disease Control and Prevention in 2016 issued guidelines intended to curb unnecessary use of opioids. The guidelines noted that other medicines could treat chronic pain without raising the risk of addiction. The Choosing Wisely campaign, run by a foundation of the American Board of Internal Medicine, also offered recommendations about limiting use of opioids. And insurers have restricted access to opioids through the prior authorization process. As a result, researchers will make their own guesses at the causes of the decline in opioid prescriptions, based on their own experiences and research interests, Dr. Stein said.
“It almost functions as a Rorschach test,” he said.
Dr. Stein’s group also looked at trends among medical specialties. They found the largest reduction between 2008-2009 and 2017-2018 among emergency physicians (70.5% drop from 99,254.5 MME to 29,234.3 MME), psychiatrists (67.2% drop from 50,464.3 MME to 16,533.0 MME) and oncologists (59.5% drop from 51,731.2 MME to 20,941.4).
Among surgeons, the RAND researchers found a drop of 49.3% from 220,764.6 to 111,904.4. Among dentists, they found a drop of 41.3% from 22,345.3 to 13,126.1.
Among pain specialists, they found a drop of 15.4% from 1,020,808.4 MME to 863,140.7 MME.
Among adult primary care clinicians, Dr. Stein and his colleagues found a drop of 40% from 651,489.4 MME in 2008-2009 to 390,841.0 MME in 2017-2018.
However, one of the groups tracked in the study increased the volume of opioid prescriptions written: advanced practice providers, among whom scripts for the drugs rose 22.7%, from 112,873.9 MME to 138,459.3 MME.
Dr. Stein said he suspects that this gain reflects a change in the nature of the practice of primary care, with nurse practitioners and physician assistants taking more active roles in treatment of patients. Some of the reduction seen among primary care clinicians who treat adults may reflect a shift in which medical personnel in a practice write the opioid prescriptions.
Still, the trends in general seen by Dr. Stein and coauthors are encouraging, even if further study of these patterns is needed, he said.
“This is one of those papers that I think potentially raises as many questions as it provides answers for,” he said.
What’s missing
Maya Hambright, MD, a family medicine physician in New York’s Hudson Valley, who has been working mainly in addiction in response to the opioid overdose crisis, observed that the drop in total prescribed volume of prescription painkillers does not necessarily translate into a reduction in use of opioids
“No one is taking fewer opioids,” Dr. Hambright told this news organization. “I can say that comfortably. They are just getting them from other sources.”
CDC data support Dr. Hambright’s view.
An estimated 100,306 people in the United States died of a drug overdose in the 12 months that ended in April 2021, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the CDC.
Dr. Hambright said more physicians need to be involved in prescribing medication-assisted treatment (MAT).
The federal government has in the past year loosened restrictions on a requirement, known as an X waiver. Certain clinicians have been exempted from training requirements, as explained in the frequently asked questions page on the Substance Abuse and Mental Health Services Administration website.
SAMHSA says legislation is required to eliminate the waiver. As of Dec. 30, 2021, more than half of the members of the U.S. House of Representatives were listed as sponsors of the Mainstreaming Addiction Treatment (MAT) Act (HR 1384), which would end the need for X waivers. The bill has the backing of 187 Democrats and 43 Republicans.
At this time, too many physicians shy away from offering MAT, Dr. Hambright said.
“People are still scared of it,” she said. “People don’t want to deal with addicts.”
But Dr. Hambright said it’s well worth the initial time invested in having the needed conversations with patients about MAT.
“Afterwards, it’s so straightforward. People feel better. They’re healthier. It’s amazing,” she said. “You’re changing lives.”
The research was supported by grants from the National Institutes of Health. Dr. Stein and coauthors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The volume of prescription opioids dispensed at retail pharmacies in the United States dropped by 21% in recent years amid efforts to reduce unnecessary use of the painkillers, but the rate of decline varied greatly among types of patients and by type of clinician, a study found.
In a brief report published by Annals of Internal Medicine, researchers from the nonprofit RAND Corp reported an analysis of opioid prescriptions from two periods, 2008-2009 and 2017-2018.
The researchers sought to assess total opioid use rather than simply track the number of pills dispensed. So they used days’ supply and total daily dose to calculate per capita morphine milligram equivalents (MME) for opioid prescriptions, write Bradley D. Stein, MD, PhD, MPH, the study’s lead author and a senior physician researcher at RAND Corp, and his coauthors in their paper.
For the study, the researchers used data from the consulting firm IQVIA, which they say covers about 90% of U.S. prescriptions. Total opioid volume per capita by prescriptions filled in retail pharmacies decreased from 951.4 MME in 2008-2009 to 749.3 MME in 2017-2018, Dr. Stein’s group found.
(In 2020, IQVIA separately said that prescription opioid use per adult in this country rose from an average of 16 pills, or 134 MMEs, in 1992 to a peak of about 55 pills a person, or 790 MMEs, in 2011. By 2019, opioid use per adult had declined to 29 pills and 366 MMEs per capita.)
The RAND report found substantial variation in opioid volume by type of insurance, including a 41.5% decline (636.5 MME to 372.6 MME) among people covered by commercial health plans. That exceeded the 27.7% drop seen for people enrolled in Medicaid (646.8 MME to 467.7 MME). The decline was smaller (17.5%; 2,780.2 MME to 2,294.2 MME) for those on Medicare, who as a group used the most opioids.
‘Almost functions as a Rorschach test’
The causes of the decline are easy to guess, although definitive conclusions are impossible, Dr. Stein told this news organization.
Significant work has been done in recent years to change attitudes about opioid prescriptions by physicians, researchers, and lawmakers. Aggressive promotion of prescription painkillers, particularly Purdue Pharma’s OxyContin, in the 1990s, is widely cited as the triggering event for the national opioid crisis.
In response, states created databases known as prescription drug monitoring programs. The Centers for Disease Control and Prevention in 2016 issued guidelines intended to curb unnecessary use of opioids. The guidelines noted that other medicines could treat chronic pain without raising the risk of addiction. The Choosing Wisely campaign, run by a foundation of the American Board of Internal Medicine, also offered recommendations about limiting use of opioids. And insurers have restricted access to opioids through the prior authorization process. As a result, researchers will make their own guesses at the causes of the decline in opioid prescriptions, based on their own experiences and research interests, Dr. Stein said.
“It almost functions as a Rorschach test,” he said.
Dr. Stein’s group also looked at trends among medical specialties. They found the largest reduction between 2008-2009 and 2017-2018 among emergency physicians (70.5% drop from 99,254.5 MME to 29,234.3 MME), psychiatrists (67.2% drop from 50,464.3 MME to 16,533.0 MME) and oncologists (59.5% drop from 51,731.2 MME to 20,941.4).
Among surgeons, the RAND researchers found a drop of 49.3% from 220,764.6 to 111,904.4. Among dentists, they found a drop of 41.3% from 22,345.3 to 13,126.1.
Among pain specialists, they found a drop of 15.4% from 1,020,808.4 MME to 863,140.7 MME.
Among adult primary care clinicians, Dr. Stein and his colleagues found a drop of 40% from 651,489.4 MME in 2008-2009 to 390,841.0 MME in 2017-2018.
However, one of the groups tracked in the study increased the volume of opioid prescriptions written: advanced practice providers, among whom scripts for the drugs rose 22.7%, from 112,873.9 MME to 138,459.3 MME.
Dr. Stein said he suspects that this gain reflects a change in the nature of the practice of primary care, with nurse practitioners and physician assistants taking more active roles in treatment of patients. Some of the reduction seen among primary care clinicians who treat adults may reflect a shift in which medical personnel in a practice write the opioid prescriptions.
Still, the trends in general seen by Dr. Stein and coauthors are encouraging, even if further study of these patterns is needed, he said.
“This is one of those papers that I think potentially raises as many questions as it provides answers for,” he said.
What’s missing
Maya Hambright, MD, a family medicine physician in New York’s Hudson Valley, who has been working mainly in addiction in response to the opioid overdose crisis, observed that the drop in total prescribed volume of prescription painkillers does not necessarily translate into a reduction in use of opioids
“No one is taking fewer opioids,” Dr. Hambright told this news organization. “I can say that comfortably. They are just getting them from other sources.”
CDC data support Dr. Hambright’s view.
An estimated 100,306 people in the United States died of a drug overdose in the 12 months that ended in April 2021, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the CDC.
Dr. Hambright said more physicians need to be involved in prescribing medication-assisted treatment (MAT).
The federal government has in the past year loosened restrictions on a requirement, known as an X waiver. Certain clinicians have been exempted from training requirements, as explained in the frequently asked questions page on the Substance Abuse and Mental Health Services Administration website.
SAMHSA says legislation is required to eliminate the waiver. As of Dec. 30, 2021, more than half of the members of the U.S. House of Representatives were listed as sponsors of the Mainstreaming Addiction Treatment (MAT) Act (HR 1384), which would end the need for X waivers. The bill has the backing of 187 Democrats and 43 Republicans.
At this time, too many physicians shy away from offering MAT, Dr. Hambright said.
“People are still scared of it,” she said. “People don’t want to deal with addicts.”
But Dr. Hambright said it’s well worth the initial time invested in having the needed conversations with patients about MAT.
“Afterwards, it’s so straightforward. People feel better. They’re healthier. It’s amazing,” she said. “You’re changing lives.”
The research was supported by grants from the National Institutes of Health. Dr. Stein and coauthors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The volume of prescription opioids dispensed at retail pharmacies in the United States dropped by 21% in recent years amid efforts to reduce unnecessary use of the painkillers, but the rate of decline varied greatly among types of patients and by type of clinician, a study found.
In a brief report published by Annals of Internal Medicine, researchers from the nonprofit RAND Corp reported an analysis of opioid prescriptions from two periods, 2008-2009 and 2017-2018.
The researchers sought to assess total opioid use rather than simply track the number of pills dispensed. So they used days’ supply and total daily dose to calculate per capita morphine milligram equivalents (MME) for opioid prescriptions, write Bradley D. Stein, MD, PhD, MPH, the study’s lead author and a senior physician researcher at RAND Corp, and his coauthors in their paper.
For the study, the researchers used data from the consulting firm IQVIA, which they say covers about 90% of U.S. prescriptions. Total opioid volume per capita by prescriptions filled in retail pharmacies decreased from 951.4 MME in 2008-2009 to 749.3 MME in 2017-2018, Dr. Stein’s group found.
(In 2020, IQVIA separately said that prescription opioid use per adult in this country rose from an average of 16 pills, or 134 MMEs, in 1992 to a peak of about 55 pills a person, or 790 MMEs, in 2011. By 2019, opioid use per adult had declined to 29 pills and 366 MMEs per capita.)
The RAND report found substantial variation in opioid volume by type of insurance, including a 41.5% decline (636.5 MME to 372.6 MME) among people covered by commercial health plans. That exceeded the 27.7% drop seen for people enrolled in Medicaid (646.8 MME to 467.7 MME). The decline was smaller (17.5%; 2,780.2 MME to 2,294.2 MME) for those on Medicare, who as a group used the most opioids.
‘Almost functions as a Rorschach test’
The causes of the decline are easy to guess, although definitive conclusions are impossible, Dr. Stein told this news organization.
Significant work has been done in recent years to change attitudes about opioid prescriptions by physicians, researchers, and lawmakers. Aggressive promotion of prescription painkillers, particularly Purdue Pharma’s OxyContin, in the 1990s, is widely cited as the triggering event for the national opioid crisis.
In response, states created databases known as prescription drug monitoring programs. The Centers for Disease Control and Prevention in 2016 issued guidelines intended to curb unnecessary use of opioids. The guidelines noted that other medicines could treat chronic pain without raising the risk of addiction. The Choosing Wisely campaign, run by a foundation of the American Board of Internal Medicine, also offered recommendations about limiting use of opioids. And insurers have restricted access to opioids through the prior authorization process. As a result, researchers will make their own guesses at the causes of the decline in opioid prescriptions, based on their own experiences and research interests, Dr. Stein said.
“It almost functions as a Rorschach test,” he said.
Dr. Stein’s group also looked at trends among medical specialties. They found the largest reduction between 2008-2009 and 2017-2018 among emergency physicians (70.5% drop from 99,254.5 MME to 29,234.3 MME), psychiatrists (67.2% drop from 50,464.3 MME to 16,533.0 MME) and oncologists (59.5% drop from 51,731.2 MME to 20,941.4).
Among surgeons, the RAND researchers found a drop of 49.3% from 220,764.6 to 111,904.4. Among dentists, they found a drop of 41.3% from 22,345.3 to 13,126.1.
Among pain specialists, they found a drop of 15.4% from 1,020,808.4 MME to 863,140.7 MME.
Among adult primary care clinicians, Dr. Stein and his colleagues found a drop of 40% from 651,489.4 MME in 2008-2009 to 390,841.0 MME in 2017-2018.
However, one of the groups tracked in the study increased the volume of opioid prescriptions written: advanced practice providers, among whom scripts for the drugs rose 22.7%, from 112,873.9 MME to 138,459.3 MME.
Dr. Stein said he suspects that this gain reflects a change in the nature of the practice of primary care, with nurse practitioners and physician assistants taking more active roles in treatment of patients. Some of the reduction seen among primary care clinicians who treat adults may reflect a shift in which medical personnel in a practice write the opioid prescriptions.
Still, the trends in general seen by Dr. Stein and coauthors are encouraging, even if further study of these patterns is needed, he said.
“This is one of those papers that I think potentially raises as many questions as it provides answers for,” he said.
What’s missing
Maya Hambright, MD, a family medicine physician in New York’s Hudson Valley, who has been working mainly in addiction in response to the opioid overdose crisis, observed that the drop in total prescribed volume of prescription painkillers does not necessarily translate into a reduction in use of opioids
“No one is taking fewer opioids,” Dr. Hambright told this news organization. “I can say that comfortably. They are just getting them from other sources.”
CDC data support Dr. Hambright’s view.
An estimated 100,306 people in the United States died of a drug overdose in the 12 months that ended in April 2021, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the CDC.
Dr. Hambright said more physicians need to be involved in prescribing medication-assisted treatment (MAT).
The federal government has in the past year loosened restrictions on a requirement, known as an X waiver. Certain clinicians have been exempted from training requirements, as explained in the frequently asked questions page on the Substance Abuse and Mental Health Services Administration website.
SAMHSA says legislation is required to eliminate the waiver. As of Dec. 30, 2021, more than half of the members of the U.S. House of Representatives were listed as sponsors of the Mainstreaming Addiction Treatment (MAT) Act (HR 1384), which would end the need for X waivers. The bill has the backing of 187 Democrats and 43 Republicans.
At this time, too many physicians shy away from offering MAT, Dr. Hambright said.
“People are still scared of it,” she said. “People don’t want to deal with addicts.”
But Dr. Hambright said it’s well worth the initial time invested in having the needed conversations with patients about MAT.
“Afterwards, it’s so straightforward. People feel better. They’re healthier. It’s amazing,” she said. “You’re changing lives.”
The research was supported by grants from the National Institutes of Health. Dr. Stein and coauthors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Infectious disease pop quiz: Clinical challenge #9 for the ObGyn
For uncomplicated chlamydia infection in a pregnant woman, what is the most appropriate treatment?
Continue to the answer...
Uncomplicated chlamydia infection in a pregnant woman should be treated with a single 1,000-mg oral dose of azithromycin. An acceptable alternative is amoxicillin 500 mg orally 3 times daily for 7 days.
In a nonpregnant patient, doxycycline 100 mg orally twice daily for 7 days is also an appropriate alternative. However, doxycycline is relatively expensive and may not be well tolerated because of gastrointestinal adverse effects. (Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Morbid Mortal Wkly Rep. 2015;64[RR3]:1-137.)
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
For uncomplicated chlamydia infection in a pregnant woman, what is the most appropriate treatment?
Continue to the answer...
Uncomplicated chlamydia infection in a pregnant woman should be treated with a single 1,000-mg oral dose of azithromycin. An acceptable alternative is amoxicillin 500 mg orally 3 times daily for 7 days.
In a nonpregnant patient, doxycycline 100 mg orally twice daily for 7 days is also an appropriate alternative. However, doxycycline is relatively expensive and may not be well tolerated because of gastrointestinal adverse effects. (Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Morbid Mortal Wkly Rep. 2015;64[RR3]:1-137.)
For uncomplicated chlamydia infection in a pregnant woman, what is the most appropriate treatment?
Continue to the answer...
Uncomplicated chlamydia infection in a pregnant woman should be treated with a single 1,000-mg oral dose of azithromycin. An acceptable alternative is amoxicillin 500 mg orally 3 times daily for 7 days.
In a nonpregnant patient, doxycycline 100 mg orally twice daily for 7 days is also an appropriate alternative. However, doxycycline is relatively expensive and may not be well tolerated because of gastrointestinal adverse effects. (Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Morbid Mortal Wkly Rep. 2015;64[RR3]:1-137.)
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
Asthma treatment does not appear to raise risk of neuropsychiatric disease
Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.
Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.
However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.
In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.
The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).
A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.
(75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).
A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.
“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.
The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.
The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.
However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.
“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.
Potential genetic predisposition may drive cases
The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).
The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..
Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.
“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.
However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.
“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.
Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.
“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.
As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.
Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.
The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.
A version of this article first appeared on Medscape.com.
Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.
Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.
However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.
In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.
The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).
A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.
(75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).
A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.
“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.
The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.
The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.
However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.
“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.
Potential genetic predisposition may drive cases
The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).
The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..
Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.
“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.
However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.
“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.
Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.
“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.
As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.
Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.
The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.
A version of this article first appeared on Medscape.com.
Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.
Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.
However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.
In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.
The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).
A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.
(75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).
A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.
“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.
The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.
The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.
However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.
“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.
Potential genetic predisposition may drive cases
The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).
The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..
Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.
“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.
However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.
“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.
Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.
“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.
As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.
Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.
The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.
A version of this article first appeared on Medscape.com.
Low BMI, weight loss predict mortality risk in ILD
A low body mass index (BMI) indicative of being underweight as well as a weight loss of 2 kg or more over the course of 1 year were both independently associated with a higher mortality risk in the following year in patients with fibrotic interstitial lung disease (ILD). In contrast, being both overweight and obese appeared to be protective against mortality at the same 1-year endpoint, according to the results of an observational, retrospective cohort study.
Compared with patients with a normal BMI, patients who were underweight at a BMI of less than 18.5 kg/m2 were over three times more likely to die at 1 year, at a hazard ratio of 3.19 (P < .001), senior author Christopher Ryerson, MD, University of British Columbia, Vancouver, and colleagues reported in the journal Chest.
In contrast, patients who were overweight with a BMI of 25-29 had roughly half the mortality risk as those who were underweight, at an HR of 0.52 (P < .001). Results were roughly similar among the patients with obesity with a BMI in excess of 30, among whom the HR for mortality at 1 year was 0.55 (P < .001), compared with those who were underweight.
“All patients with fibrotic ILD should still engage in exercise and eat an appropriate diet and it is still okay if you are obese and lose weight as a consequence of these lifestyle choices,” Dr. Ryerson told this news organization. “But physicians should be concerned about patients who have severe ILD and who start to lose weight unintentionally since this often represents end-stage fibrosis or some other major comorbidity such as cancer.”
Two large cohorts
Patients from two large cohorts, including the six-center Canadian Registry for Pulmonary Fibrosis (CARE-PF) and the ILD registry at the University of California, San Francisco, were enrolled in the study. A total of 1,786 patients were included from the CARE-PF registry, which served as the derivation cohort, while another 1,779 patients from the UCSF registry served as the validation cohort. In the CARE-PF cohort, 21% of all ILD patients experienced a weight loss of at least 1 kg in the first year of follow-up, including 31% of patients with idiopathic pulmonary fibrosis (IPF).
“Fewer patients experienced a weight loss of at least 1 kg during the first year of the study period in the UCSF cohort,” the authors noted, at only 12% of all ILD patients, some 14% of those with IPF losing at least 1 kg of weight over the course of the year. At 2 years’ follow-up, 35% of all ILD patients had lost at least 1 kg, as had 46% of all IPF patients. Looking at BMI, “a higher value was associated with decreased 1-year mortality in both cohorts on unadjusted analysis,” the investigators observed.
In the CARE-PF cohort, the HR for 1-year mortality was 0.96 per unit difference in BMI (P < .001), while in the UCSF cohort, the HR for 1-year mortality was exactly the same, at 0.96 per unit difference in BMI (P < .001). The authors then adjusted findings for the ILD-GAP index, which included gender, age, and physiology index. After adjusting for this index, the HR for 1-year mortality in the CARE-PF cohort was 0.93 per unit change in BMI (95% CI, 0.90-0.967; P < .001), while in the UCSF cohort, the HR was 0.96 per unit change in BMI (95% CI, 0.94-0.98; P = .001).
Indeed, each 1-kg change above a BMI of 30, adjusted for the ILD-GAP index, was associated with a reduced risk of mortality at 1 year in both cohorts, at an HR of 0.98 (P = .001) in the CARE-PF cohort and an HR of 0.98 (P < .001) in the UCSF cohort. In contrast, patients who experienced a BMI weight loss of 2 kg or more within 1 year had a 41% increased risk of death in the subsequent year after adjusting for the ILD-GAP index and baseline BMI category, at an HR of 1.41 (P = .04). “The absolute change in mortality is much smaller than this,” Dr. Ryerson acknowledged.
“However, the magnitude [in mortality risk] did impress us and this illustrates how weight loss is a frequent consequence of end-stage disease which is something that we have all observed clinically as well,” he added.
Mortality risk plateaued in patients with a greater weight loss, the investigators observed, and there was no association between weight and subsequent 1-year mortality in either cohort on unadjusted analysis.
On the other hand, being underweight was associated with between a 13% and 16% higher mortality risk at 1 year after adjusting for the ILD-GAP, at an HR of 0.84 per 10 kg (P = .001) in the CARE-PF cohort and an HR of 0.87 per 10 kg (P < .001) in the UCSF cohort. “Results were similar in the two studied cohorts, suggesting a robust and generalizable association of both low BMI and weight loss with mortality,” the authors emphasized.
“Together these studies highlight the potential link between obesity and ILD pathogenesis and further suggest the possibility that nutritional support may have a more specific and important role in the management of fibrotic ILD,” the authors wrote. Dr. Ryerson in turn noted that being able to determine mortality risk more accurately than current mortality risk prediction models are able to do is very helpful when dealing with what are sometimes life-and-death decisions.
He also said that having more insight into a patient’s prognosis can change how physicians manage patients with respect to either transplantation or palliation and potentially the need to be more aggressive with pharmacotherapy as well.
Addressing weight loss
Asked to comment on the findings, Elizabeth Volkmann, MD, associate professor of medicine, University of California, Los Angeles, said that this was a very important study and something that she feels does not get adequate attention in clinical practice.
“Weight loss and malnutrition occur in many patients with ILD due to various factors such as gastrointestinal side effects from antifibrotic therapies, decreased oral intake due to psychosocial issues including depression, and increased caloric requirements due to increased work of breathing,” she said in an interview. That said, weight loss and malnutrition are still often underaddressed during clinical encounters for patients with ILD where the focus is on lung health.
“This study illuminates the importance of addressing weight loss in all patients with ILD as it can contribute to heightened risk of mortality,” Dr. Volkmann reemphasized. Dr. Volkmann and colleagues themselves recently reported that radiographic progression of scleroderma lung disease over the course of 1-2 years is associated with an increased risk of long-term mortality, based on two independent studies of systemic sclerosis–interstitial lung disease with extensive follow-up.
Over 8 years of follow-up, patients in the Scleroderma Lung Study II who exhibited an increase of 2% or more in the QILD score – a score that reflects the sum of all abnormally classified scores, including those for fibrosis, ground glass opacity, and honeycombing – for the whole lung at 24 months had an almost fourfold increased risk in mortality, which was significant (P = .014).
The association of an increase in the QILD of at least 2% at 12 months was suggestive in its association with mortality in the SLS I cohort at 12 years of follow-up, a finding that suggests that radiographic progression measured at 2 years is a better predictor of long-term mortality than at 1 year, as the authors concluded.
The CARR-PF is funded by Boehringer Ingelheim. Dr. Ryerson reported receiving personal fees from Boehringer Ingelheim. Dr. Volkmann consults or has received speaker fees from Boehringer Ingelheim and has received grant support from Kadmon and Horizon Therapeutics.
A version of this article first appeared on Medscape.com.
A low body mass index (BMI) indicative of being underweight as well as a weight loss of 2 kg or more over the course of 1 year were both independently associated with a higher mortality risk in the following year in patients with fibrotic interstitial lung disease (ILD). In contrast, being both overweight and obese appeared to be protective against mortality at the same 1-year endpoint, according to the results of an observational, retrospective cohort study.
Compared with patients with a normal BMI, patients who were underweight at a BMI of less than 18.5 kg/m2 were over three times more likely to die at 1 year, at a hazard ratio of 3.19 (P < .001), senior author Christopher Ryerson, MD, University of British Columbia, Vancouver, and colleagues reported in the journal Chest.
In contrast, patients who were overweight with a BMI of 25-29 had roughly half the mortality risk as those who were underweight, at an HR of 0.52 (P < .001). Results were roughly similar among the patients with obesity with a BMI in excess of 30, among whom the HR for mortality at 1 year was 0.55 (P < .001), compared with those who were underweight.
“All patients with fibrotic ILD should still engage in exercise and eat an appropriate diet and it is still okay if you are obese and lose weight as a consequence of these lifestyle choices,” Dr. Ryerson told this news organization. “But physicians should be concerned about patients who have severe ILD and who start to lose weight unintentionally since this often represents end-stage fibrosis or some other major comorbidity such as cancer.”
Two large cohorts
Patients from two large cohorts, including the six-center Canadian Registry for Pulmonary Fibrosis (CARE-PF) and the ILD registry at the University of California, San Francisco, were enrolled in the study. A total of 1,786 patients were included from the CARE-PF registry, which served as the derivation cohort, while another 1,779 patients from the UCSF registry served as the validation cohort. In the CARE-PF cohort, 21% of all ILD patients experienced a weight loss of at least 1 kg in the first year of follow-up, including 31% of patients with idiopathic pulmonary fibrosis (IPF).
“Fewer patients experienced a weight loss of at least 1 kg during the first year of the study period in the UCSF cohort,” the authors noted, at only 12% of all ILD patients, some 14% of those with IPF losing at least 1 kg of weight over the course of the year. At 2 years’ follow-up, 35% of all ILD patients had lost at least 1 kg, as had 46% of all IPF patients. Looking at BMI, “a higher value was associated with decreased 1-year mortality in both cohorts on unadjusted analysis,” the investigators observed.
In the CARE-PF cohort, the HR for 1-year mortality was 0.96 per unit difference in BMI (P < .001), while in the UCSF cohort, the HR for 1-year mortality was exactly the same, at 0.96 per unit difference in BMI (P < .001). The authors then adjusted findings for the ILD-GAP index, which included gender, age, and physiology index. After adjusting for this index, the HR for 1-year mortality in the CARE-PF cohort was 0.93 per unit change in BMI (95% CI, 0.90-0.967; P < .001), while in the UCSF cohort, the HR was 0.96 per unit change in BMI (95% CI, 0.94-0.98; P = .001).
Indeed, each 1-kg change above a BMI of 30, adjusted for the ILD-GAP index, was associated with a reduced risk of mortality at 1 year in both cohorts, at an HR of 0.98 (P = .001) in the CARE-PF cohort and an HR of 0.98 (P < .001) in the UCSF cohort. In contrast, patients who experienced a BMI weight loss of 2 kg or more within 1 year had a 41% increased risk of death in the subsequent year after adjusting for the ILD-GAP index and baseline BMI category, at an HR of 1.41 (P = .04). “The absolute change in mortality is much smaller than this,” Dr. Ryerson acknowledged.
“However, the magnitude [in mortality risk] did impress us and this illustrates how weight loss is a frequent consequence of end-stage disease which is something that we have all observed clinically as well,” he added.
Mortality risk plateaued in patients with a greater weight loss, the investigators observed, and there was no association between weight and subsequent 1-year mortality in either cohort on unadjusted analysis.
On the other hand, being underweight was associated with between a 13% and 16% higher mortality risk at 1 year after adjusting for the ILD-GAP, at an HR of 0.84 per 10 kg (P = .001) in the CARE-PF cohort and an HR of 0.87 per 10 kg (P < .001) in the UCSF cohort. “Results were similar in the two studied cohorts, suggesting a robust and generalizable association of both low BMI and weight loss with mortality,” the authors emphasized.
“Together these studies highlight the potential link between obesity and ILD pathogenesis and further suggest the possibility that nutritional support may have a more specific and important role in the management of fibrotic ILD,” the authors wrote. Dr. Ryerson in turn noted that being able to determine mortality risk more accurately than current mortality risk prediction models are able to do is very helpful when dealing with what are sometimes life-and-death decisions.
He also said that having more insight into a patient’s prognosis can change how physicians manage patients with respect to either transplantation or palliation and potentially the need to be more aggressive with pharmacotherapy as well.
Addressing weight loss
Asked to comment on the findings, Elizabeth Volkmann, MD, associate professor of medicine, University of California, Los Angeles, said that this was a very important study and something that she feels does not get adequate attention in clinical practice.
“Weight loss and malnutrition occur in many patients with ILD due to various factors such as gastrointestinal side effects from antifibrotic therapies, decreased oral intake due to psychosocial issues including depression, and increased caloric requirements due to increased work of breathing,” she said in an interview. That said, weight loss and malnutrition are still often underaddressed during clinical encounters for patients with ILD where the focus is on lung health.
“This study illuminates the importance of addressing weight loss in all patients with ILD as it can contribute to heightened risk of mortality,” Dr. Volkmann reemphasized. Dr. Volkmann and colleagues themselves recently reported that radiographic progression of scleroderma lung disease over the course of 1-2 years is associated with an increased risk of long-term mortality, based on two independent studies of systemic sclerosis–interstitial lung disease with extensive follow-up.
Over 8 years of follow-up, patients in the Scleroderma Lung Study II who exhibited an increase of 2% or more in the QILD score – a score that reflects the sum of all abnormally classified scores, including those for fibrosis, ground glass opacity, and honeycombing – for the whole lung at 24 months had an almost fourfold increased risk in mortality, which was significant (P = .014).
The association of an increase in the QILD of at least 2% at 12 months was suggestive in its association with mortality in the SLS I cohort at 12 years of follow-up, a finding that suggests that radiographic progression measured at 2 years is a better predictor of long-term mortality than at 1 year, as the authors concluded.
The CARR-PF is funded by Boehringer Ingelheim. Dr. Ryerson reported receiving personal fees from Boehringer Ingelheim. Dr. Volkmann consults or has received speaker fees from Boehringer Ingelheim and has received grant support from Kadmon and Horizon Therapeutics.
A version of this article first appeared on Medscape.com.
A low body mass index (BMI) indicative of being underweight as well as a weight loss of 2 kg or more over the course of 1 year were both independently associated with a higher mortality risk in the following year in patients with fibrotic interstitial lung disease (ILD). In contrast, being both overweight and obese appeared to be protective against mortality at the same 1-year endpoint, according to the results of an observational, retrospective cohort study.
Compared with patients with a normal BMI, patients who were underweight at a BMI of less than 18.5 kg/m2 were over three times more likely to die at 1 year, at a hazard ratio of 3.19 (P < .001), senior author Christopher Ryerson, MD, University of British Columbia, Vancouver, and colleagues reported in the journal Chest.
In contrast, patients who were overweight with a BMI of 25-29 had roughly half the mortality risk as those who were underweight, at an HR of 0.52 (P < .001). Results were roughly similar among the patients with obesity with a BMI in excess of 30, among whom the HR for mortality at 1 year was 0.55 (P < .001), compared with those who were underweight.
“All patients with fibrotic ILD should still engage in exercise and eat an appropriate diet and it is still okay if you are obese and lose weight as a consequence of these lifestyle choices,” Dr. Ryerson told this news organization. “But physicians should be concerned about patients who have severe ILD and who start to lose weight unintentionally since this often represents end-stage fibrosis or some other major comorbidity such as cancer.”
Two large cohorts
Patients from two large cohorts, including the six-center Canadian Registry for Pulmonary Fibrosis (CARE-PF) and the ILD registry at the University of California, San Francisco, were enrolled in the study. A total of 1,786 patients were included from the CARE-PF registry, which served as the derivation cohort, while another 1,779 patients from the UCSF registry served as the validation cohort. In the CARE-PF cohort, 21% of all ILD patients experienced a weight loss of at least 1 kg in the first year of follow-up, including 31% of patients with idiopathic pulmonary fibrosis (IPF).
“Fewer patients experienced a weight loss of at least 1 kg during the first year of the study period in the UCSF cohort,” the authors noted, at only 12% of all ILD patients, some 14% of those with IPF losing at least 1 kg of weight over the course of the year. At 2 years’ follow-up, 35% of all ILD patients had lost at least 1 kg, as had 46% of all IPF patients. Looking at BMI, “a higher value was associated with decreased 1-year mortality in both cohorts on unadjusted analysis,” the investigators observed.
In the CARE-PF cohort, the HR for 1-year mortality was 0.96 per unit difference in BMI (P < .001), while in the UCSF cohort, the HR for 1-year mortality was exactly the same, at 0.96 per unit difference in BMI (P < .001). The authors then adjusted findings for the ILD-GAP index, which included gender, age, and physiology index. After adjusting for this index, the HR for 1-year mortality in the CARE-PF cohort was 0.93 per unit change in BMI (95% CI, 0.90-0.967; P < .001), while in the UCSF cohort, the HR was 0.96 per unit change in BMI (95% CI, 0.94-0.98; P = .001).
Indeed, each 1-kg change above a BMI of 30, adjusted for the ILD-GAP index, was associated with a reduced risk of mortality at 1 year in both cohorts, at an HR of 0.98 (P = .001) in the CARE-PF cohort and an HR of 0.98 (P < .001) in the UCSF cohort. In contrast, patients who experienced a BMI weight loss of 2 kg or more within 1 year had a 41% increased risk of death in the subsequent year after adjusting for the ILD-GAP index and baseline BMI category, at an HR of 1.41 (P = .04). “The absolute change in mortality is much smaller than this,” Dr. Ryerson acknowledged.
“However, the magnitude [in mortality risk] did impress us and this illustrates how weight loss is a frequent consequence of end-stage disease which is something that we have all observed clinically as well,” he added.
Mortality risk plateaued in patients with a greater weight loss, the investigators observed, and there was no association between weight and subsequent 1-year mortality in either cohort on unadjusted analysis.
On the other hand, being underweight was associated with between a 13% and 16% higher mortality risk at 1 year after adjusting for the ILD-GAP, at an HR of 0.84 per 10 kg (P = .001) in the CARE-PF cohort and an HR of 0.87 per 10 kg (P < .001) in the UCSF cohort. “Results were similar in the two studied cohorts, suggesting a robust and generalizable association of both low BMI and weight loss with mortality,” the authors emphasized.
“Together these studies highlight the potential link between obesity and ILD pathogenesis and further suggest the possibility that nutritional support may have a more specific and important role in the management of fibrotic ILD,” the authors wrote. Dr. Ryerson in turn noted that being able to determine mortality risk more accurately than current mortality risk prediction models are able to do is very helpful when dealing with what are sometimes life-and-death decisions.
He also said that having more insight into a patient’s prognosis can change how physicians manage patients with respect to either transplantation or palliation and potentially the need to be more aggressive with pharmacotherapy as well.
Addressing weight loss
Asked to comment on the findings, Elizabeth Volkmann, MD, associate professor of medicine, University of California, Los Angeles, said that this was a very important study and something that she feels does not get adequate attention in clinical practice.
“Weight loss and malnutrition occur in many patients with ILD due to various factors such as gastrointestinal side effects from antifibrotic therapies, decreased oral intake due to psychosocial issues including depression, and increased caloric requirements due to increased work of breathing,” she said in an interview. That said, weight loss and malnutrition are still often underaddressed during clinical encounters for patients with ILD where the focus is on lung health.
“This study illuminates the importance of addressing weight loss in all patients with ILD as it can contribute to heightened risk of mortality,” Dr. Volkmann reemphasized. Dr. Volkmann and colleagues themselves recently reported that radiographic progression of scleroderma lung disease over the course of 1-2 years is associated with an increased risk of long-term mortality, based on two independent studies of systemic sclerosis–interstitial lung disease with extensive follow-up.
Over 8 years of follow-up, patients in the Scleroderma Lung Study II who exhibited an increase of 2% or more in the QILD score – a score that reflects the sum of all abnormally classified scores, including those for fibrosis, ground glass opacity, and honeycombing – for the whole lung at 24 months had an almost fourfold increased risk in mortality, which was significant (P = .014).
The association of an increase in the QILD of at least 2% at 12 months was suggestive in its association with mortality in the SLS I cohort at 12 years of follow-up, a finding that suggests that radiographic progression measured at 2 years is a better predictor of long-term mortality than at 1 year, as the authors concluded.
The CARR-PF is funded by Boehringer Ingelheim. Dr. Ryerson reported receiving personal fees from Boehringer Ingelheim. Dr. Volkmann consults or has received speaker fees from Boehringer Ingelheim and has received grant support from Kadmon and Horizon Therapeutics.
A version of this article first appeared on Medscape.com.
FROM CHEST
Were these true medical miracles? Doctors disagree
It was a freezing December day, and two young brothers were playing outside near a swimming pool when the younger boy, a 3-year-old toddler, fell into the water.
The 7-year-old immediately jumped into the pool to save his brother and was able to pull the toddler to the pool steps where the boy’s head was above water. But the icy temperatures overcame the older brother and he drifted underwater.
“Despite being at the forefront of medicine, what we don’t understand often exceeds what we do understand,” said Harley Rotbart, MD, author of “Miracles We Have Seen” (Health Communications: Deerfield Beach, Fla., 2016).
Paramedics arrived to find both boys unconscious and rushed them to the Children’s Hospital of Philadelphia. The younger boy regained consciousness in the ICU and recovered. The 7-year-old, however, was unresponsive and remained in a coma, said Dr. Rotbart a pediatrician and author based in Denver.
Family members stayed at the boy’s bedside and prayed. But after several weeks, the child’s condition remained unchanged. His parents began to discuss ending life support and organ donation. Then late one night, as Dr. Rotbart sat reading to the unconscious patient, the little boy squeezed his hand. In disbelief, Dr. Rotbart told all of his colleagues about the squeeze the next morning. Everyone attributed the movement to an involuntary muscle spasm, he said. After all, every test and scan showed the boy had no brain function.
But later that day, the child grasped another staff member’s hand. Shortly after that, he squeezed in response to a command. Dr. Rotbart and his staff were stunned, but cautious about feeling too much hope.
Days later, the child opened his eyes. Then, he smiled. His parents were overjoyed.
“When he walked out of the hospital more than 2 months after the near-drowning and his heroic rescue of his little brother, we all cheered and cried,” Dr. Rotbart wrote in his book. “We cried many times in the weeks preceding, and I still cry whenever I recall this story.”
The experience, which happened years ago when Dr. Rotbart was a trainee, has stayed with the pediatrician his entire career.
“His awakening was seemingly impossible – and then it happened,” Dr. Rotbart said. “Despite being at the forefront of medicine and science, what we don’t understand often exceeds what we do understand. And even when we think we understand, we are frequently proven wrong.”
For many, Dr. Rotbart’s experience raises questions about the existence of medical miracles.
Do physicians believe in medical miracles? The answers are diverse.
“I have no doubt that extraordinary outcomes happen where patients who are overwhelmingly expected not to survive, do,” says Eric Beam, MD, a hospitalist based in San Diego. “That’s one of the reasons we choose our words very carefully in our conversations with patients and their families and remember that nothing is 0%, and nothing is 100%. But doctors tend to treat situations that are 99.9% as absolute. I don’t think you can practice medicine with the hope or expectation that every case you see has the potential to beat the odds – or be a medical miracle.”
Disappearing cancer hailed as ‘miracle’
In 2003, physicians projected that Joseph Rick, 40, had just a few months to live. His mucosal melanoma had spread throughout his body, progressing even after several surgeries, radiation therapy, and a combination of chemotherapy agents, recalled Antoni Ribas, MD, PhD, an oncologist and director of the tumor immunology program at Jonsson Comprehensive Cancer Center in Los Angeles.
Mr. Rick’s melanoma had spread to his intestines with traces on his stomach and bladder. Tumors were present on his liver, lungs, and pancreas. Rick bought a grave and prepared for the worst, he recounted in a Cancer Research Institute video. But his fate took a turn when he enrolled in an experimental drug trial in December 2003. The phase 1 trial was for a new immune modulating antibody, called an anti–CTLA-4 antibody, said Dr. Ribas, who conducted the trial.
Over the next few weeks and months, all areas of Rick’s melanoma metastases disappeared. By 2009, he was in remission. He has lived the rest of his life with no evidence of melanoma, according to Dr. Ribas.
Mr. Rick’s case has been referenced throughout literature and news stories as a “medical miracle” and a “cancer miracle.”
Does Dr. Ribas think the case was a medical miracle?
“The response in Joseph Rick was what happened in 10%-15% of patients who received anti-CTLA-4 therapy,” Dr. Ribas said. “These were not miracles. These patients responded because their immune system trying to attack the cancer had been stuck at the CTLA-4 checkpoint. Blocking this checkpoint allowed their immune system to proceed to attack and kill cancer cells anywhere in the body.”
The scientific basis of this therapy was work by University of Texas MD Anderson Cancer Center immunologist James Allison, PhD, that had been done 5 years earlier in mouse models, where giving an anti–CTLA-4 antibody to mice allowed them to reject several implanted cancers, Dr. Ribas explained. Dr. Allison received the 2018 Nobel Prize in Physiology or Medicine for this work, subsequently opening the door for what we now call “immune checkpoint blockade therapy for cancer.” Dr. Ribas added.
“We tend to call miracles good things that we do not understand how they happened,” Dr. Ribas said. “From the human observation perspective, there have been plenty of medical miracles. However, each one has a specific biological mechanism that led to improvement in a patient. In cancer treatment, early studies using the immune system resulted in occasional patients having tumor responses and long-term benefits.
“With the increased understanding of how the immune system interacts with cancers, which is based on remarkable progress in understanding how the immune system works generated over the past several decades, these ‘miracles’ become specific mechanisms leading to response to cancer, which can then be replicated in other patients.”
Patient defies odds after 45 minutes without heartbeat
Florida ob.gyn. Michael Fleischer, MD, had just performed a routine repeat cesarean birth, delivering a healthy baby girl. His patient, Ruby, had a history of high blood pressure but medication taken during the pregnancy had kept her levels stabilized.
In the waiting room, Dr. Fleischer informed Ruby’s large family of the good news. He was planning to head home early that day when he heard his name being called over the hospital’s loudspeaker. Ruby had stopped breathing.
“The anesthesiologist was with her and had immediately intubated her,” Dr. Fleischer said. “We checked to make sure there was no problems or bleeding from the C-section, but everything was completely fine. However, we couldn’t keep her blood pressure stable.”
Dr. Fleischer suspected the respiratory arrest was caused by either an amniotic fluid embolism or a pulmonary embolism. Intubation continued and physicians gave Ruby medication to stabilize her blood pressure. Then suddenly, Ruby’s heart stopped.
Dr. Fleischer and other doctors began compressions, which they continued for 30 minutes. They shocked Ruby with defibrillator paddles multiple times, but there was no change.
“I was already thinking, this is hopeless, there’s nothing we can do,” he said. “The writing is on the wall. She’s going to die.”
Dr. Fleischer spoke to Ruby’s family and explained the tragic turn of events. Relatives were distraught and tearfully visited Ruby to say their goodbyes. They prayed and cried. Eventually, physicians ceased compressions. Ruby had gone 45 minutes without a pulse. The EKG was still showing some irregularity, FDr. leischer said, but no rhythm. Physicians kept Ruby intubated as they waited for the background electrical activity to fade. As they watched the screen in anguish, there was suddenly a blip on the heart rate monitor. Then another and another. Within seconds, Ruby’s heart went back into sinus rhythm.
“We were in disbelief,” Dr. Fleischer said. “We did some tests and put her in the ICU, and she was fine. Usually, after doing compressions on anyone, you’d have bruising or broken ribs. She had nothing. She just woke up and said: ‘What am I doing here? Let me go see my baby.’ ”
Ruby fully recovered, and 3 days later, she went home with her newborn.
While the recovery was unbelievable, Dr. Fleischer stopped short of calling it a medical miracle. There were scientific contributors to her survival: she was immediately intubated when she stopped breathing and compressions were started as soon as her heart stopped.
However, Dr. Fleischer said the fact that lifesaving measures had ended, and Ruby revived on her own was indeed, miraculous.
“It wasn’t like we were doing compressions and brought her back,” he said. “I can scientifically explain things in my mind, except for that. That when we finally stopped and took our hands off her, that’s when something changed. That’s when she came back.”
How do ‘medical miracles’ impact physicians?
When Dr. Rotbart was writing his book, which includes physician essays from across the world, he was struck by how many of the events happened decades earlier.
“This is another testament to the powerful impact these experiences have on those witnessing them,” he said. “In many cases, physicians describing events occurring years ago noted that those early memories served to give them hope as they encountered new, seemingly hopeless cases in subsequent years. Some contributors wrote that the ‘miracle experience’ actually directed them in their choice of specialty and has influenced much of their professional decision-making throughout their careers. Others draw on those miraculous moments at times when they themselves feel hopeless in the face of adversity and tragedy.”
Dr. Fleischer said that, although Ruby’s story has stayed with him, his mindset or practice style didn’t necessarily change after the experience.
“I’m not sure if it’s affected me because I haven’t been in that situation again,” he said. “I’m in the middle. I would never rule out anything, but I’m not going to base how I practice on the hope for a medical miracle.”
In a recent opinion piece for the New York Times, pulmonary and critical care physician, Daniela Lamas, MD, wrote about the sometimes negative effects of miracle cases on physicians. Such experiences for instance, can lead to a greater drive to beat the odds in future cases, which can sometimes lead to false hope, protracted critical care admissions, and futile procedures.
“After all, in most cases in the ICU, our initial prognoses are correct,” she wrote. “So there’s a risk to standing at the bedside, thinking about that one patient who made it home despite our predictions. We can give that experience too much weight in influencing our decisions and recommendations.”
Dr. Beam said unexpected outcomes – particularly in the age of COVID-19 – can certainly make physicians think differently about life-sustaining measures and when to discuss end-of-life care with family members. In his own practice, Dr. Beam has encountered unexpected COVID recoveries. Now, he generally gives extremely ill COVID patients a little more time to see if their bodies recover.
“It remains true that people who are really sick with COVID, who are on ventilated or who are requiring a lot of up respiratory support, they don’t do well on average,” he said. “But it is [also] true that there are a handful of people who get to that point and do come back to 80% or 90% of where they were. It makes you think twice.”
What to do when parents hope for a miracle
In his palliative care practice, Nashville, Tenn., surgeon Myrick Shinall Jr., MD, PhD, regularly encounters families and patients who wish for a medical miracle.
“It happens pretty often from a palliative care perspective,” he said. “What I have experienced the most is a patient with a severe brain injury who we don’t believe is recoverable. The medical team is discussing with the family that it is probably time to discontinue the ventilator. In those situations, families will often talk about wanting us to continue on [our life-sustaining efforts] in the hopes that a miracle will happen.”
Dr. Shinall and Trevor Bibler, PhD, recently authored two articles about best practices for responding to patients who hope for a miracle. The first one, published in the American Journal of Bioethics, is directed toward bioethicists; the second article, in the Journal of Pain and Symptom Management, targets clinicians.
A primary takeaway from the papers is that health professionals should recognize that hope for a miracle may mean different things to different people, said Dr. Bibler, an ethicist and assistant professor at Baylor College of Medicine, Houston. Some patients may have an innocuous hope for a miracle without a religious connotation, whereas others may have a firm conviction in their idea of God, their spirituality, and a concrete vision of the miracle.
“To hear that a family or patient is hoping for a miracle, one shouldn’t assume they already know what the patient or the family might mean by that,” Dr. Bibler said. “If a patient were to say, ‘I hope for a miracle,’ you might ask: ‘What do you mean by a miracle?’ Health professionals should feel empowered to ask that question.”
Health care professionals should explore a patient’s hope for a miracle, be nonjudgmental, ask clarifying questions, restate what the patient has said, and delve into the patient’s world view on death and dying, according to Dr. Bibler’s analyses. In some cases, it may be helpful to include a chaplain or the presence of a theology outsider in discussions.
When his patients and their families raise the subject of miracles, Dr. Shinall said he inquires what a miracle would look like in their opinion and tries to gauge how much of the assertion is a general hope compared with a firm belief.
“I try to work with them to make sure they understand doctors’ decisions and recommendations are based on what we know and can predict from our medical experience,” he said. “And that there’s nothing we’re going to do to prevent a miracle from happening, but that that can’t be our medical plan – to wait for a miracle.”
Despite the many patients and families Dr. Shinall has encountered who hope for a miracle, he has never experienced a case that he would describe as a medical miracle, he said.
Dr. Rotbart believes all physicians struggle with finding balance in how far to push in hope of a miracle and when to let go.
“Miracles, whether they happen to us, or we hear of them from colleagues or we read about them, should humble us as physicians,” he said. “I have come to believe that what we don’t know or don’t understand about medicine, medical miracles, or life in general, isn‘t necessarily cause for fear, and can even be reason for hope.
“Medicine has come a long way since Hippocrates’ theory of The Four Humors and The Four Temperaments, yet we still have much to learn about the workings of the human body. As physicians, we should take comfort in how much we don’t know because that allows us to share hope with our patients and, occasionally, makes medical miracles possible.”
A version of this article first appeared on Medscape.com.
It was a freezing December day, and two young brothers were playing outside near a swimming pool when the younger boy, a 3-year-old toddler, fell into the water.
The 7-year-old immediately jumped into the pool to save his brother and was able to pull the toddler to the pool steps where the boy’s head was above water. But the icy temperatures overcame the older brother and he drifted underwater.
“Despite being at the forefront of medicine, what we don’t understand often exceeds what we do understand,” said Harley Rotbart, MD, author of “Miracles We Have Seen” (Health Communications: Deerfield Beach, Fla., 2016).
Paramedics arrived to find both boys unconscious and rushed them to the Children’s Hospital of Philadelphia. The younger boy regained consciousness in the ICU and recovered. The 7-year-old, however, was unresponsive and remained in a coma, said Dr. Rotbart a pediatrician and author based in Denver.
Family members stayed at the boy’s bedside and prayed. But after several weeks, the child’s condition remained unchanged. His parents began to discuss ending life support and organ donation. Then late one night, as Dr. Rotbart sat reading to the unconscious patient, the little boy squeezed his hand. In disbelief, Dr. Rotbart told all of his colleagues about the squeeze the next morning. Everyone attributed the movement to an involuntary muscle spasm, he said. After all, every test and scan showed the boy had no brain function.
But later that day, the child grasped another staff member’s hand. Shortly after that, he squeezed in response to a command. Dr. Rotbart and his staff were stunned, but cautious about feeling too much hope.
Days later, the child opened his eyes. Then, he smiled. His parents were overjoyed.
“When he walked out of the hospital more than 2 months after the near-drowning and his heroic rescue of his little brother, we all cheered and cried,” Dr. Rotbart wrote in his book. “We cried many times in the weeks preceding, and I still cry whenever I recall this story.”
The experience, which happened years ago when Dr. Rotbart was a trainee, has stayed with the pediatrician his entire career.
“His awakening was seemingly impossible – and then it happened,” Dr. Rotbart said. “Despite being at the forefront of medicine and science, what we don’t understand often exceeds what we do understand. And even when we think we understand, we are frequently proven wrong.”
For many, Dr. Rotbart’s experience raises questions about the existence of medical miracles.
Do physicians believe in medical miracles? The answers are diverse.
“I have no doubt that extraordinary outcomes happen where patients who are overwhelmingly expected not to survive, do,” says Eric Beam, MD, a hospitalist based in San Diego. “That’s one of the reasons we choose our words very carefully in our conversations with patients and their families and remember that nothing is 0%, and nothing is 100%. But doctors tend to treat situations that are 99.9% as absolute. I don’t think you can practice medicine with the hope or expectation that every case you see has the potential to beat the odds – or be a medical miracle.”
Disappearing cancer hailed as ‘miracle’
In 2003, physicians projected that Joseph Rick, 40, had just a few months to live. His mucosal melanoma had spread throughout his body, progressing even after several surgeries, radiation therapy, and a combination of chemotherapy agents, recalled Antoni Ribas, MD, PhD, an oncologist and director of the tumor immunology program at Jonsson Comprehensive Cancer Center in Los Angeles.
Mr. Rick’s melanoma had spread to his intestines with traces on his stomach and bladder. Tumors were present on his liver, lungs, and pancreas. Rick bought a grave and prepared for the worst, he recounted in a Cancer Research Institute video. But his fate took a turn when he enrolled in an experimental drug trial in December 2003. The phase 1 trial was for a new immune modulating antibody, called an anti–CTLA-4 antibody, said Dr. Ribas, who conducted the trial.
Over the next few weeks and months, all areas of Rick’s melanoma metastases disappeared. By 2009, he was in remission. He has lived the rest of his life with no evidence of melanoma, according to Dr. Ribas.
Mr. Rick’s case has been referenced throughout literature and news stories as a “medical miracle” and a “cancer miracle.”
Does Dr. Ribas think the case was a medical miracle?
“The response in Joseph Rick was what happened in 10%-15% of patients who received anti-CTLA-4 therapy,” Dr. Ribas said. “These were not miracles. These patients responded because their immune system trying to attack the cancer had been stuck at the CTLA-4 checkpoint. Blocking this checkpoint allowed their immune system to proceed to attack and kill cancer cells anywhere in the body.”
The scientific basis of this therapy was work by University of Texas MD Anderson Cancer Center immunologist James Allison, PhD, that had been done 5 years earlier in mouse models, where giving an anti–CTLA-4 antibody to mice allowed them to reject several implanted cancers, Dr. Ribas explained. Dr. Allison received the 2018 Nobel Prize in Physiology or Medicine for this work, subsequently opening the door for what we now call “immune checkpoint blockade therapy for cancer.” Dr. Ribas added.
“We tend to call miracles good things that we do not understand how they happened,” Dr. Ribas said. “From the human observation perspective, there have been plenty of medical miracles. However, each one has a specific biological mechanism that led to improvement in a patient. In cancer treatment, early studies using the immune system resulted in occasional patients having tumor responses and long-term benefits.
“With the increased understanding of how the immune system interacts with cancers, which is based on remarkable progress in understanding how the immune system works generated over the past several decades, these ‘miracles’ become specific mechanisms leading to response to cancer, which can then be replicated in other patients.”
Patient defies odds after 45 minutes without heartbeat
Florida ob.gyn. Michael Fleischer, MD, had just performed a routine repeat cesarean birth, delivering a healthy baby girl. His patient, Ruby, had a history of high blood pressure but medication taken during the pregnancy had kept her levels stabilized.
In the waiting room, Dr. Fleischer informed Ruby’s large family of the good news. He was planning to head home early that day when he heard his name being called over the hospital’s loudspeaker. Ruby had stopped breathing.
“The anesthesiologist was with her and had immediately intubated her,” Dr. Fleischer said. “We checked to make sure there was no problems or bleeding from the C-section, but everything was completely fine. However, we couldn’t keep her blood pressure stable.”
Dr. Fleischer suspected the respiratory arrest was caused by either an amniotic fluid embolism or a pulmonary embolism. Intubation continued and physicians gave Ruby medication to stabilize her blood pressure. Then suddenly, Ruby’s heart stopped.
Dr. Fleischer and other doctors began compressions, which they continued for 30 minutes. They shocked Ruby with defibrillator paddles multiple times, but there was no change.
“I was already thinking, this is hopeless, there’s nothing we can do,” he said. “The writing is on the wall. She’s going to die.”
Dr. Fleischer spoke to Ruby’s family and explained the tragic turn of events. Relatives were distraught and tearfully visited Ruby to say their goodbyes. They prayed and cried. Eventually, physicians ceased compressions. Ruby had gone 45 minutes without a pulse. The EKG was still showing some irregularity, FDr. leischer said, but no rhythm. Physicians kept Ruby intubated as they waited for the background electrical activity to fade. As they watched the screen in anguish, there was suddenly a blip on the heart rate monitor. Then another and another. Within seconds, Ruby’s heart went back into sinus rhythm.
“We were in disbelief,” Dr. Fleischer said. “We did some tests and put her in the ICU, and she was fine. Usually, after doing compressions on anyone, you’d have bruising or broken ribs. She had nothing. She just woke up and said: ‘What am I doing here? Let me go see my baby.’ ”
Ruby fully recovered, and 3 days later, she went home with her newborn.
While the recovery was unbelievable, Dr. Fleischer stopped short of calling it a medical miracle. There were scientific contributors to her survival: she was immediately intubated when she stopped breathing and compressions were started as soon as her heart stopped.
However, Dr. Fleischer said the fact that lifesaving measures had ended, and Ruby revived on her own was indeed, miraculous.
“It wasn’t like we were doing compressions and brought her back,” he said. “I can scientifically explain things in my mind, except for that. That when we finally stopped and took our hands off her, that’s when something changed. That’s when she came back.”
How do ‘medical miracles’ impact physicians?
When Dr. Rotbart was writing his book, which includes physician essays from across the world, he was struck by how many of the events happened decades earlier.
“This is another testament to the powerful impact these experiences have on those witnessing them,” he said. “In many cases, physicians describing events occurring years ago noted that those early memories served to give them hope as they encountered new, seemingly hopeless cases in subsequent years. Some contributors wrote that the ‘miracle experience’ actually directed them in their choice of specialty and has influenced much of their professional decision-making throughout their careers. Others draw on those miraculous moments at times when they themselves feel hopeless in the face of adversity and tragedy.”
Dr. Fleischer said that, although Ruby’s story has stayed with him, his mindset or practice style didn’t necessarily change after the experience.
“I’m not sure if it’s affected me because I haven’t been in that situation again,” he said. “I’m in the middle. I would never rule out anything, but I’m not going to base how I practice on the hope for a medical miracle.”
In a recent opinion piece for the New York Times, pulmonary and critical care physician, Daniela Lamas, MD, wrote about the sometimes negative effects of miracle cases on physicians. Such experiences for instance, can lead to a greater drive to beat the odds in future cases, which can sometimes lead to false hope, protracted critical care admissions, and futile procedures.
“After all, in most cases in the ICU, our initial prognoses are correct,” she wrote. “So there’s a risk to standing at the bedside, thinking about that one patient who made it home despite our predictions. We can give that experience too much weight in influencing our decisions and recommendations.”
Dr. Beam said unexpected outcomes – particularly in the age of COVID-19 – can certainly make physicians think differently about life-sustaining measures and when to discuss end-of-life care with family members. In his own practice, Dr. Beam has encountered unexpected COVID recoveries. Now, he generally gives extremely ill COVID patients a little more time to see if their bodies recover.
“It remains true that people who are really sick with COVID, who are on ventilated or who are requiring a lot of up respiratory support, they don’t do well on average,” he said. “But it is [also] true that there are a handful of people who get to that point and do come back to 80% or 90% of where they were. It makes you think twice.”
What to do when parents hope for a miracle
In his palliative care practice, Nashville, Tenn., surgeon Myrick Shinall Jr., MD, PhD, regularly encounters families and patients who wish for a medical miracle.
“It happens pretty often from a palliative care perspective,” he said. “What I have experienced the most is a patient with a severe brain injury who we don’t believe is recoverable. The medical team is discussing with the family that it is probably time to discontinue the ventilator. In those situations, families will often talk about wanting us to continue on [our life-sustaining efforts] in the hopes that a miracle will happen.”
Dr. Shinall and Trevor Bibler, PhD, recently authored two articles about best practices for responding to patients who hope for a miracle. The first one, published in the American Journal of Bioethics, is directed toward bioethicists; the second article, in the Journal of Pain and Symptom Management, targets clinicians.
A primary takeaway from the papers is that health professionals should recognize that hope for a miracle may mean different things to different people, said Dr. Bibler, an ethicist and assistant professor at Baylor College of Medicine, Houston. Some patients may have an innocuous hope for a miracle without a religious connotation, whereas others may have a firm conviction in their idea of God, their spirituality, and a concrete vision of the miracle.
“To hear that a family or patient is hoping for a miracle, one shouldn’t assume they already know what the patient or the family might mean by that,” Dr. Bibler said. “If a patient were to say, ‘I hope for a miracle,’ you might ask: ‘What do you mean by a miracle?’ Health professionals should feel empowered to ask that question.”
Health care professionals should explore a patient’s hope for a miracle, be nonjudgmental, ask clarifying questions, restate what the patient has said, and delve into the patient’s world view on death and dying, according to Dr. Bibler’s analyses. In some cases, it may be helpful to include a chaplain or the presence of a theology outsider in discussions.
When his patients and their families raise the subject of miracles, Dr. Shinall said he inquires what a miracle would look like in their opinion and tries to gauge how much of the assertion is a general hope compared with a firm belief.
“I try to work with them to make sure they understand doctors’ decisions and recommendations are based on what we know and can predict from our medical experience,” he said. “And that there’s nothing we’re going to do to prevent a miracle from happening, but that that can’t be our medical plan – to wait for a miracle.”
Despite the many patients and families Dr. Shinall has encountered who hope for a miracle, he has never experienced a case that he would describe as a medical miracle, he said.
Dr. Rotbart believes all physicians struggle with finding balance in how far to push in hope of a miracle and when to let go.
“Miracles, whether they happen to us, or we hear of them from colleagues or we read about them, should humble us as physicians,” he said. “I have come to believe that what we don’t know or don’t understand about medicine, medical miracles, or life in general, isn‘t necessarily cause for fear, and can even be reason for hope.
“Medicine has come a long way since Hippocrates’ theory of The Four Humors and The Four Temperaments, yet we still have much to learn about the workings of the human body. As physicians, we should take comfort in how much we don’t know because that allows us to share hope with our patients and, occasionally, makes medical miracles possible.”
A version of this article first appeared on Medscape.com.
It was a freezing December day, and two young brothers were playing outside near a swimming pool when the younger boy, a 3-year-old toddler, fell into the water.
The 7-year-old immediately jumped into the pool to save his brother and was able to pull the toddler to the pool steps where the boy’s head was above water. But the icy temperatures overcame the older brother and he drifted underwater.
“Despite being at the forefront of medicine, what we don’t understand often exceeds what we do understand,” said Harley Rotbart, MD, author of “Miracles We Have Seen” (Health Communications: Deerfield Beach, Fla., 2016).
Paramedics arrived to find both boys unconscious and rushed them to the Children’s Hospital of Philadelphia. The younger boy regained consciousness in the ICU and recovered. The 7-year-old, however, was unresponsive and remained in a coma, said Dr. Rotbart a pediatrician and author based in Denver.
Family members stayed at the boy’s bedside and prayed. But after several weeks, the child’s condition remained unchanged. His parents began to discuss ending life support and organ donation. Then late one night, as Dr. Rotbart sat reading to the unconscious patient, the little boy squeezed his hand. In disbelief, Dr. Rotbart told all of his colleagues about the squeeze the next morning. Everyone attributed the movement to an involuntary muscle spasm, he said. After all, every test and scan showed the boy had no brain function.
But later that day, the child grasped another staff member’s hand. Shortly after that, he squeezed in response to a command. Dr. Rotbart and his staff were stunned, but cautious about feeling too much hope.
Days later, the child opened his eyes. Then, he smiled. His parents were overjoyed.
“When he walked out of the hospital more than 2 months after the near-drowning and his heroic rescue of his little brother, we all cheered and cried,” Dr. Rotbart wrote in his book. “We cried many times in the weeks preceding, and I still cry whenever I recall this story.”
The experience, which happened years ago when Dr. Rotbart was a trainee, has stayed with the pediatrician his entire career.
“His awakening was seemingly impossible – and then it happened,” Dr. Rotbart said. “Despite being at the forefront of medicine and science, what we don’t understand often exceeds what we do understand. And even when we think we understand, we are frequently proven wrong.”
For many, Dr. Rotbart’s experience raises questions about the existence of medical miracles.
Do physicians believe in medical miracles? The answers are diverse.
“I have no doubt that extraordinary outcomes happen where patients who are overwhelmingly expected not to survive, do,” says Eric Beam, MD, a hospitalist based in San Diego. “That’s one of the reasons we choose our words very carefully in our conversations with patients and their families and remember that nothing is 0%, and nothing is 100%. But doctors tend to treat situations that are 99.9% as absolute. I don’t think you can practice medicine with the hope or expectation that every case you see has the potential to beat the odds – or be a medical miracle.”
Disappearing cancer hailed as ‘miracle’
In 2003, physicians projected that Joseph Rick, 40, had just a few months to live. His mucosal melanoma had spread throughout his body, progressing even after several surgeries, radiation therapy, and a combination of chemotherapy agents, recalled Antoni Ribas, MD, PhD, an oncologist and director of the tumor immunology program at Jonsson Comprehensive Cancer Center in Los Angeles.
Mr. Rick’s melanoma had spread to his intestines with traces on his stomach and bladder. Tumors were present on his liver, lungs, and pancreas. Rick bought a grave and prepared for the worst, he recounted in a Cancer Research Institute video. But his fate took a turn when he enrolled in an experimental drug trial in December 2003. The phase 1 trial was for a new immune modulating antibody, called an anti–CTLA-4 antibody, said Dr. Ribas, who conducted the trial.
Over the next few weeks and months, all areas of Rick’s melanoma metastases disappeared. By 2009, he was in remission. He has lived the rest of his life with no evidence of melanoma, according to Dr. Ribas.
Mr. Rick’s case has been referenced throughout literature and news stories as a “medical miracle” and a “cancer miracle.”
Does Dr. Ribas think the case was a medical miracle?
“The response in Joseph Rick was what happened in 10%-15% of patients who received anti-CTLA-4 therapy,” Dr. Ribas said. “These were not miracles. These patients responded because their immune system trying to attack the cancer had been stuck at the CTLA-4 checkpoint. Blocking this checkpoint allowed their immune system to proceed to attack and kill cancer cells anywhere in the body.”
The scientific basis of this therapy was work by University of Texas MD Anderson Cancer Center immunologist James Allison, PhD, that had been done 5 years earlier in mouse models, where giving an anti–CTLA-4 antibody to mice allowed them to reject several implanted cancers, Dr. Ribas explained. Dr. Allison received the 2018 Nobel Prize in Physiology or Medicine for this work, subsequently opening the door for what we now call “immune checkpoint blockade therapy for cancer.” Dr. Ribas added.
“We tend to call miracles good things that we do not understand how they happened,” Dr. Ribas said. “From the human observation perspective, there have been plenty of medical miracles. However, each one has a specific biological mechanism that led to improvement in a patient. In cancer treatment, early studies using the immune system resulted in occasional patients having tumor responses and long-term benefits.
“With the increased understanding of how the immune system interacts with cancers, which is based on remarkable progress in understanding how the immune system works generated over the past several decades, these ‘miracles’ become specific mechanisms leading to response to cancer, which can then be replicated in other patients.”
Patient defies odds after 45 minutes without heartbeat
Florida ob.gyn. Michael Fleischer, MD, had just performed a routine repeat cesarean birth, delivering a healthy baby girl. His patient, Ruby, had a history of high blood pressure but medication taken during the pregnancy had kept her levels stabilized.
In the waiting room, Dr. Fleischer informed Ruby’s large family of the good news. He was planning to head home early that day when he heard his name being called over the hospital’s loudspeaker. Ruby had stopped breathing.
“The anesthesiologist was with her and had immediately intubated her,” Dr. Fleischer said. “We checked to make sure there was no problems or bleeding from the C-section, but everything was completely fine. However, we couldn’t keep her blood pressure stable.”
Dr. Fleischer suspected the respiratory arrest was caused by either an amniotic fluid embolism or a pulmonary embolism. Intubation continued and physicians gave Ruby medication to stabilize her blood pressure. Then suddenly, Ruby’s heart stopped.
Dr. Fleischer and other doctors began compressions, which they continued for 30 minutes. They shocked Ruby with defibrillator paddles multiple times, but there was no change.
“I was already thinking, this is hopeless, there’s nothing we can do,” he said. “The writing is on the wall. She’s going to die.”
Dr. Fleischer spoke to Ruby’s family and explained the tragic turn of events. Relatives were distraught and tearfully visited Ruby to say their goodbyes. They prayed and cried. Eventually, physicians ceased compressions. Ruby had gone 45 minutes without a pulse. The EKG was still showing some irregularity, FDr. leischer said, but no rhythm. Physicians kept Ruby intubated as they waited for the background electrical activity to fade. As they watched the screen in anguish, there was suddenly a blip on the heart rate monitor. Then another and another. Within seconds, Ruby’s heart went back into sinus rhythm.
“We were in disbelief,” Dr. Fleischer said. “We did some tests and put her in the ICU, and she was fine. Usually, after doing compressions on anyone, you’d have bruising or broken ribs. She had nothing. She just woke up and said: ‘What am I doing here? Let me go see my baby.’ ”
Ruby fully recovered, and 3 days later, she went home with her newborn.
While the recovery was unbelievable, Dr. Fleischer stopped short of calling it a medical miracle. There were scientific contributors to her survival: she was immediately intubated when she stopped breathing and compressions were started as soon as her heart stopped.
However, Dr. Fleischer said the fact that lifesaving measures had ended, and Ruby revived on her own was indeed, miraculous.
“It wasn’t like we were doing compressions and brought her back,” he said. “I can scientifically explain things in my mind, except for that. That when we finally stopped and took our hands off her, that’s when something changed. That’s when she came back.”
How do ‘medical miracles’ impact physicians?
When Dr. Rotbart was writing his book, which includes physician essays from across the world, he was struck by how many of the events happened decades earlier.
“This is another testament to the powerful impact these experiences have on those witnessing them,” he said. “In many cases, physicians describing events occurring years ago noted that those early memories served to give them hope as they encountered new, seemingly hopeless cases in subsequent years. Some contributors wrote that the ‘miracle experience’ actually directed them in their choice of specialty and has influenced much of their professional decision-making throughout their careers. Others draw on those miraculous moments at times when they themselves feel hopeless in the face of adversity and tragedy.”
Dr. Fleischer said that, although Ruby’s story has stayed with him, his mindset or practice style didn’t necessarily change after the experience.
“I’m not sure if it’s affected me because I haven’t been in that situation again,” he said. “I’m in the middle. I would never rule out anything, but I’m not going to base how I practice on the hope for a medical miracle.”
In a recent opinion piece for the New York Times, pulmonary and critical care physician, Daniela Lamas, MD, wrote about the sometimes negative effects of miracle cases on physicians. Such experiences for instance, can lead to a greater drive to beat the odds in future cases, which can sometimes lead to false hope, protracted critical care admissions, and futile procedures.
“After all, in most cases in the ICU, our initial prognoses are correct,” she wrote. “So there’s a risk to standing at the bedside, thinking about that one patient who made it home despite our predictions. We can give that experience too much weight in influencing our decisions and recommendations.”
Dr. Beam said unexpected outcomes – particularly in the age of COVID-19 – can certainly make physicians think differently about life-sustaining measures and when to discuss end-of-life care with family members. In his own practice, Dr. Beam has encountered unexpected COVID recoveries. Now, he generally gives extremely ill COVID patients a little more time to see if their bodies recover.
“It remains true that people who are really sick with COVID, who are on ventilated or who are requiring a lot of up respiratory support, they don’t do well on average,” he said. “But it is [also] true that there are a handful of people who get to that point and do come back to 80% or 90% of where they were. It makes you think twice.”
What to do when parents hope for a miracle
In his palliative care practice, Nashville, Tenn., surgeon Myrick Shinall Jr., MD, PhD, regularly encounters families and patients who wish for a medical miracle.
“It happens pretty often from a palliative care perspective,” he said. “What I have experienced the most is a patient with a severe brain injury who we don’t believe is recoverable. The medical team is discussing with the family that it is probably time to discontinue the ventilator. In those situations, families will often talk about wanting us to continue on [our life-sustaining efforts] in the hopes that a miracle will happen.”
Dr. Shinall and Trevor Bibler, PhD, recently authored two articles about best practices for responding to patients who hope for a miracle. The first one, published in the American Journal of Bioethics, is directed toward bioethicists; the second article, in the Journal of Pain and Symptom Management, targets clinicians.
A primary takeaway from the papers is that health professionals should recognize that hope for a miracle may mean different things to different people, said Dr. Bibler, an ethicist and assistant professor at Baylor College of Medicine, Houston. Some patients may have an innocuous hope for a miracle without a religious connotation, whereas others may have a firm conviction in their idea of God, their spirituality, and a concrete vision of the miracle.
“To hear that a family or patient is hoping for a miracle, one shouldn’t assume they already know what the patient or the family might mean by that,” Dr. Bibler said. “If a patient were to say, ‘I hope for a miracle,’ you might ask: ‘What do you mean by a miracle?’ Health professionals should feel empowered to ask that question.”
Health care professionals should explore a patient’s hope for a miracle, be nonjudgmental, ask clarifying questions, restate what the patient has said, and delve into the patient’s world view on death and dying, according to Dr. Bibler’s analyses. In some cases, it may be helpful to include a chaplain or the presence of a theology outsider in discussions.
When his patients and their families raise the subject of miracles, Dr. Shinall said he inquires what a miracle would look like in their opinion and tries to gauge how much of the assertion is a general hope compared with a firm belief.
“I try to work with them to make sure they understand doctors’ decisions and recommendations are based on what we know and can predict from our medical experience,” he said. “And that there’s nothing we’re going to do to prevent a miracle from happening, but that that can’t be our medical plan – to wait for a miracle.”
Despite the many patients and families Dr. Shinall has encountered who hope for a miracle, he has never experienced a case that he would describe as a medical miracle, he said.
Dr. Rotbart believes all physicians struggle with finding balance in how far to push in hope of a miracle and when to let go.
“Miracles, whether they happen to us, or we hear of them from colleagues or we read about them, should humble us as physicians,” he said. “I have come to believe that what we don’t know or don’t understand about medicine, medical miracles, or life in general, isn‘t necessarily cause for fear, and can even be reason for hope.
“Medicine has come a long way since Hippocrates’ theory of The Four Humors and The Four Temperaments, yet we still have much to learn about the workings of the human body. As physicians, we should take comfort in how much we don’t know because that allows us to share hope with our patients and, occasionally, makes medical miracles possible.”
A version of this article first appeared on Medscape.com.
Quality measurement in gastroenterology: A vision for the future
Modern efforts to monitor and improve quality in health care can trace their roots to the early 20th century. At that time, hospitals initiated mechanisms to ensure standard practices for privileging clinicians, reporting medical records and clinical data, and establishing supervised diagnostic facilities. Years later, Avedis Donabedian published “Evaluating the Quality of Medical Care,” which outlined how health care should be measured across three areas – structure, process, and outcome – and became a foundational rubric for assessing quality in medicine.
Over the ensuing decades, with the rise of professional society guidelines and increasing government involvement in the reimbursement of health care, establishing benchmarks and tracking clinical performance has become increasingly important. The passage of the Affordable Care Act subsequently established a formal, legislative mandate for assessing clinical quality tied to reimbursement. Although the context, consequences, and details for reporting have evolved, quality tracking is now firmly entrenched across clinical practice, including gastroenterology. One such mechanism for this is the Merit-Based Incentive Payment System (MIPS), which is a quality payment program (QPP) administered by the Centers for Medicare & Medicaid Services. Today, both government and private payers are assessing measurements and improvements of quality to satisfy the Quintuple Aim of achieving better health outcomes, seeking efficient cost of care, improving patient experience, improving provider experience, and enhancing equity through the reduction health inequalities.
As we transition from a fee-based to a value-based care model, several important developments relevant to the practicing gastroenterologist are likely to occur as the broader landscape of quality reporting will continue shifting. This article will outline a vision of the future in quality measurement for gastroenterology.
Gastroenterologists have relatively few specialty-specific measures on which to report. The widespread use of the adenoma detection rate for screening colonoscopy does represent a success in quality improvement because it is easily calculated, is reproducible, and has been consistently associated with clinical outcomes. But the overall measure set is limited to screening colonoscopy and the management of viral hepatitis, meaning large areas of our practice are not included in this set. Developing new metrics related to broader areas of practice will be necessary to address this current shortcoming and increase the impact of quality programs to clinicians. Indeed, a recent environmental scan performed by the Core Quality Measures Collaborative, a public-private coalition of leaders working to facilitate measure alignment, proposed future areas for development, including gastroesophageal reflux disease, nonalcoholic fatty liver disease, and medication management.
The American Gastroenterological Association, through its defined process of guideline-to-measure development, has responded by creating metrics for the management of acute pancreatitis, Lynch syndrome testing, and eradicating Helicobacter pylori in the context of gastric intestinal metaplasia; additionally, previously defined measures exist for Barrett’s esophagus and inflammatory bowel disease. Therefore, gastroenterologists can expect to report on an expanding collection of measures in the future.
However, recognizing that not all measures may be equally applicable across populations and acknowledging the importance of risk adjustment, incorporating at least an assessment for risk stratification in their future development is vital. Specifically, social risk factors will need to be accounted for during development in ways that might include risk adjustment or stratification by groups. Increasing data demonstrate that clinician performance can vary by population served and that social determinants of health (SDoH) should be incorporated into an assessment of outcomes. Risk stratification may allow clinicians or practices to report outcomes by group without jeopardy of incurring performance-based penalties. However, the ultimate goal should be reducing inequities and closing care gaps rather than inadvertently lowering the bar for clinicians who primarily treat disenfranchised populations. Eventually, any new measures aiming to be included in a QPP require formal validity testing, which can delay their inclusion in such a set. Yet including stratification in their development will provide a more robust and accurate assessment of quality of care delivered according to one’s catchment and help serve to minimize the effects of SDoH.
Another way that quality measurement may account for a more comprehensive assessment of care delivered is by bundling similarly provided services, even those across multiple specialties. Such a future model is the MIPS Value Pathways, currently under development by CMS. While the exact make-up and reporting structure remains to be determined, a group of related metrics – for example, for colonic health – would likely be grouped together. This model might include an evaluation of a practice’s performance in screening colonoscopy, Lynch testing practices, and inflammatory bowel disease management, which could also be relevant to surgeons, pathologists, and oncologists. This paradigm could serve to increase quality alignment across specialties and reinforce a commitment toward improving care delivery and fulfill a value-based mandate.
Within this framework, though, a shared challenge across specialties exists for the capture and reporting of clinical data. The financial and time costs for quality reporting are well documented, therefore any future vision of quality must address means to ease this reporting burden. Accounting for this would be especially impactful to independent as well as small- to moderate-sized practices, which must provide their own resources for collecting and reporting, with the QPP payment adjustments often insufficient to replace lost revenue or expenses. Some administrative relief has been provided by CMS during the current COVID-19 pandemic, but this focused on allowing select clinicians to avoid reporting rather than addressing the fundamental challenges presented by extracting and documenting quality measures. Moving forward, an increasing emphasis will likely be on the use of artificial intelligence (AI), such as natural language processing, combined with discrete code extraction for tracking performance. While AI has the advantage of a more hands-free approach, such a system would itself require monitoring for performance to avoid unintended consequences.
Ultimately, providing high-quality care and improving patient outcomes are universal goals, though demonstrating this aspiration by reporting on quality metrics can be challenging. Quality measurement, though, is now firmly integrated into the fabric of clinical medicine. In the future, more facets of practice will be measured, patient-level factors and cross specialty reporting will increasingly be emphasized, and administrative burdens will be reduced.
Dr. Leiman is assistant professor of medicine at Duke University, Durham, N.C., cochair of the Core Quality Measure Collaborative Gastroenterology Workgroup, and chair of the AGA’s Quality Committee. Dr. Freedman is medical director, SE Territory, Aetna/CVS Health and cochair of the Core Quality Measure Collaborative Gastroenterology Workgroup. Dr. Anjou is a practicing clinical gastroenterologist at Connecticut GI, Torrington, and recent member of the AGA Quality Committee. The authors reported no conflicts related to this article.
Modern efforts to monitor and improve quality in health care can trace their roots to the early 20th century. At that time, hospitals initiated mechanisms to ensure standard practices for privileging clinicians, reporting medical records and clinical data, and establishing supervised diagnostic facilities. Years later, Avedis Donabedian published “Evaluating the Quality of Medical Care,” which outlined how health care should be measured across three areas – structure, process, and outcome – and became a foundational rubric for assessing quality in medicine.
Over the ensuing decades, with the rise of professional society guidelines and increasing government involvement in the reimbursement of health care, establishing benchmarks and tracking clinical performance has become increasingly important. The passage of the Affordable Care Act subsequently established a formal, legislative mandate for assessing clinical quality tied to reimbursement. Although the context, consequences, and details for reporting have evolved, quality tracking is now firmly entrenched across clinical practice, including gastroenterology. One such mechanism for this is the Merit-Based Incentive Payment System (MIPS), which is a quality payment program (QPP) administered by the Centers for Medicare & Medicaid Services. Today, both government and private payers are assessing measurements and improvements of quality to satisfy the Quintuple Aim of achieving better health outcomes, seeking efficient cost of care, improving patient experience, improving provider experience, and enhancing equity through the reduction health inequalities.
As we transition from a fee-based to a value-based care model, several important developments relevant to the practicing gastroenterologist are likely to occur as the broader landscape of quality reporting will continue shifting. This article will outline a vision of the future in quality measurement for gastroenterology.
Gastroenterologists have relatively few specialty-specific measures on which to report. The widespread use of the adenoma detection rate for screening colonoscopy does represent a success in quality improvement because it is easily calculated, is reproducible, and has been consistently associated with clinical outcomes. But the overall measure set is limited to screening colonoscopy and the management of viral hepatitis, meaning large areas of our practice are not included in this set. Developing new metrics related to broader areas of practice will be necessary to address this current shortcoming and increase the impact of quality programs to clinicians. Indeed, a recent environmental scan performed by the Core Quality Measures Collaborative, a public-private coalition of leaders working to facilitate measure alignment, proposed future areas for development, including gastroesophageal reflux disease, nonalcoholic fatty liver disease, and medication management.
The American Gastroenterological Association, through its defined process of guideline-to-measure development, has responded by creating metrics for the management of acute pancreatitis, Lynch syndrome testing, and eradicating Helicobacter pylori in the context of gastric intestinal metaplasia; additionally, previously defined measures exist for Barrett’s esophagus and inflammatory bowel disease. Therefore, gastroenterologists can expect to report on an expanding collection of measures in the future.
However, recognizing that not all measures may be equally applicable across populations and acknowledging the importance of risk adjustment, incorporating at least an assessment for risk stratification in their future development is vital. Specifically, social risk factors will need to be accounted for during development in ways that might include risk adjustment or stratification by groups. Increasing data demonstrate that clinician performance can vary by population served and that social determinants of health (SDoH) should be incorporated into an assessment of outcomes. Risk stratification may allow clinicians or practices to report outcomes by group without jeopardy of incurring performance-based penalties. However, the ultimate goal should be reducing inequities and closing care gaps rather than inadvertently lowering the bar for clinicians who primarily treat disenfranchised populations. Eventually, any new measures aiming to be included in a QPP require formal validity testing, which can delay their inclusion in such a set. Yet including stratification in their development will provide a more robust and accurate assessment of quality of care delivered according to one’s catchment and help serve to minimize the effects of SDoH.
Another way that quality measurement may account for a more comprehensive assessment of care delivered is by bundling similarly provided services, even those across multiple specialties. Such a future model is the MIPS Value Pathways, currently under development by CMS. While the exact make-up and reporting structure remains to be determined, a group of related metrics – for example, for colonic health – would likely be grouped together. This model might include an evaluation of a practice’s performance in screening colonoscopy, Lynch testing practices, and inflammatory bowel disease management, which could also be relevant to surgeons, pathologists, and oncologists. This paradigm could serve to increase quality alignment across specialties and reinforce a commitment toward improving care delivery and fulfill a value-based mandate.
Within this framework, though, a shared challenge across specialties exists for the capture and reporting of clinical data. The financial and time costs for quality reporting are well documented, therefore any future vision of quality must address means to ease this reporting burden. Accounting for this would be especially impactful to independent as well as small- to moderate-sized practices, which must provide their own resources for collecting and reporting, with the QPP payment adjustments often insufficient to replace lost revenue or expenses. Some administrative relief has been provided by CMS during the current COVID-19 pandemic, but this focused on allowing select clinicians to avoid reporting rather than addressing the fundamental challenges presented by extracting and documenting quality measures. Moving forward, an increasing emphasis will likely be on the use of artificial intelligence (AI), such as natural language processing, combined with discrete code extraction for tracking performance. While AI has the advantage of a more hands-free approach, such a system would itself require monitoring for performance to avoid unintended consequences.
Ultimately, providing high-quality care and improving patient outcomes are universal goals, though demonstrating this aspiration by reporting on quality metrics can be challenging. Quality measurement, though, is now firmly integrated into the fabric of clinical medicine. In the future, more facets of practice will be measured, patient-level factors and cross specialty reporting will increasingly be emphasized, and administrative burdens will be reduced.
Dr. Leiman is assistant professor of medicine at Duke University, Durham, N.C., cochair of the Core Quality Measure Collaborative Gastroenterology Workgroup, and chair of the AGA’s Quality Committee. Dr. Freedman is medical director, SE Territory, Aetna/CVS Health and cochair of the Core Quality Measure Collaborative Gastroenterology Workgroup. Dr. Anjou is a practicing clinical gastroenterologist at Connecticut GI, Torrington, and recent member of the AGA Quality Committee. The authors reported no conflicts related to this article.
Modern efforts to monitor and improve quality in health care can trace their roots to the early 20th century. At that time, hospitals initiated mechanisms to ensure standard practices for privileging clinicians, reporting medical records and clinical data, and establishing supervised diagnostic facilities. Years later, Avedis Donabedian published “Evaluating the Quality of Medical Care,” which outlined how health care should be measured across three areas – structure, process, and outcome – and became a foundational rubric for assessing quality in medicine.
Over the ensuing decades, with the rise of professional society guidelines and increasing government involvement in the reimbursement of health care, establishing benchmarks and tracking clinical performance has become increasingly important. The passage of the Affordable Care Act subsequently established a formal, legislative mandate for assessing clinical quality tied to reimbursement. Although the context, consequences, and details for reporting have evolved, quality tracking is now firmly entrenched across clinical practice, including gastroenterology. One such mechanism for this is the Merit-Based Incentive Payment System (MIPS), which is a quality payment program (QPP) administered by the Centers for Medicare & Medicaid Services. Today, both government and private payers are assessing measurements and improvements of quality to satisfy the Quintuple Aim of achieving better health outcomes, seeking efficient cost of care, improving patient experience, improving provider experience, and enhancing equity through the reduction health inequalities.
As we transition from a fee-based to a value-based care model, several important developments relevant to the practicing gastroenterologist are likely to occur as the broader landscape of quality reporting will continue shifting. This article will outline a vision of the future in quality measurement for gastroenterology.
Gastroenterologists have relatively few specialty-specific measures on which to report. The widespread use of the adenoma detection rate for screening colonoscopy does represent a success in quality improvement because it is easily calculated, is reproducible, and has been consistently associated with clinical outcomes. But the overall measure set is limited to screening colonoscopy and the management of viral hepatitis, meaning large areas of our practice are not included in this set. Developing new metrics related to broader areas of practice will be necessary to address this current shortcoming and increase the impact of quality programs to clinicians. Indeed, a recent environmental scan performed by the Core Quality Measures Collaborative, a public-private coalition of leaders working to facilitate measure alignment, proposed future areas for development, including gastroesophageal reflux disease, nonalcoholic fatty liver disease, and medication management.
The American Gastroenterological Association, through its defined process of guideline-to-measure development, has responded by creating metrics for the management of acute pancreatitis, Lynch syndrome testing, and eradicating Helicobacter pylori in the context of gastric intestinal metaplasia; additionally, previously defined measures exist for Barrett’s esophagus and inflammatory bowel disease. Therefore, gastroenterologists can expect to report on an expanding collection of measures in the future.
However, recognizing that not all measures may be equally applicable across populations and acknowledging the importance of risk adjustment, incorporating at least an assessment for risk stratification in their future development is vital. Specifically, social risk factors will need to be accounted for during development in ways that might include risk adjustment or stratification by groups. Increasing data demonstrate that clinician performance can vary by population served and that social determinants of health (SDoH) should be incorporated into an assessment of outcomes. Risk stratification may allow clinicians or practices to report outcomes by group without jeopardy of incurring performance-based penalties. However, the ultimate goal should be reducing inequities and closing care gaps rather than inadvertently lowering the bar for clinicians who primarily treat disenfranchised populations. Eventually, any new measures aiming to be included in a QPP require formal validity testing, which can delay their inclusion in such a set. Yet including stratification in their development will provide a more robust and accurate assessment of quality of care delivered according to one’s catchment and help serve to minimize the effects of SDoH.
Another way that quality measurement may account for a more comprehensive assessment of care delivered is by bundling similarly provided services, even those across multiple specialties. Such a future model is the MIPS Value Pathways, currently under development by CMS. While the exact make-up and reporting structure remains to be determined, a group of related metrics – for example, for colonic health – would likely be grouped together. This model might include an evaluation of a practice’s performance in screening colonoscopy, Lynch testing practices, and inflammatory bowel disease management, which could also be relevant to surgeons, pathologists, and oncologists. This paradigm could serve to increase quality alignment across specialties and reinforce a commitment toward improving care delivery and fulfill a value-based mandate.
Within this framework, though, a shared challenge across specialties exists for the capture and reporting of clinical data. The financial and time costs for quality reporting are well documented, therefore any future vision of quality must address means to ease this reporting burden. Accounting for this would be especially impactful to independent as well as small- to moderate-sized practices, which must provide their own resources for collecting and reporting, with the QPP payment adjustments often insufficient to replace lost revenue or expenses. Some administrative relief has been provided by CMS during the current COVID-19 pandemic, but this focused on allowing select clinicians to avoid reporting rather than addressing the fundamental challenges presented by extracting and documenting quality measures. Moving forward, an increasing emphasis will likely be on the use of artificial intelligence (AI), such as natural language processing, combined with discrete code extraction for tracking performance. While AI has the advantage of a more hands-free approach, such a system would itself require monitoring for performance to avoid unintended consequences.
Ultimately, providing high-quality care and improving patient outcomes are universal goals, though demonstrating this aspiration by reporting on quality metrics can be challenging. Quality measurement, though, is now firmly integrated into the fabric of clinical medicine. In the future, more facets of practice will be measured, patient-level factors and cross specialty reporting will increasingly be emphasized, and administrative burdens will be reduced.
Dr. Leiman is assistant professor of medicine at Duke University, Durham, N.C., cochair of the Core Quality Measure Collaborative Gastroenterology Workgroup, and chair of the AGA’s Quality Committee. Dr. Freedman is medical director, SE Territory, Aetna/CVS Health and cochair of the Core Quality Measure Collaborative Gastroenterology Workgroup. Dr. Anjou is a practicing clinical gastroenterologist at Connecticut GI, Torrington, and recent member of the AGA Quality Committee. The authors reported no conflicts related to this article.