For understanding the evolution in child neurology over the past 30 years, it would make sense to start with the science, particularly genetics, that have led to treatments and even cures for numerous inherited diseases over that time. When John Bodensteiner, MD, a pillar in the field of child neurology, was asked, he started with something different.

Parent advocacy accelerates advances in rare pediatric diseases

For the progress in many of the rare diseases seen by child neurologists in the last few decades, Dr. Bodensteiner first acknowledged parent support. “The concept was simple initially. For so many of these relatively rare diseases, like the Rett and Sturge-Weber syndromes, parents were learning of them for the first time. The support groups helped parents understand they were not alone. But it then evolved,” recalled Dr. Bodensteiner, who has been a professor of pediatrics and neurology at numerous institutions, most recently the Mayo Clinic in Rochester, Minn.

Many of these support groups first formed, or at least gained momentum, in the 1990s. “As the support groups grew, the members expanded their role to support research, in addition to supporting each other. They ended up volunteering their own data, providing more information about the epidemiology and disease course. They offered tissue samples for experimental studies. They enrolled their children in trials. And they raised funds,” Dr. Bodensteiner explained.

The impact of this advocacy has been enormous, according to Dr. Bodensteiner. As an expert in neuromuscular diseases, he worked directly with several of these groups.

Although the growth in parent advocacy took place in parallel with major advances in genetics that were driving new insights into disease pathophysiology, Dr. Bodensteiner characterized parent advocates as important partners in accelerating the transition of new information to clinical utility. He suggested that there is little doubt about the importance of their role in moving the science forward by drawing attention to rare disorders that had few, if any, treatment options at the time the advocacy groups were formed.

Since the 1990s, the list of childhood neurologic diseases for which there has been meaningful progress is long. Dr. Bodensteiner selected several examples. For Rett syndrome, key molecular mechanisms have now been isolated, providing meaningful targets that show potential for treatment. For spinal muscular atrophy (SMA), therapies have become available, one of which involves gene replacement that appears to provide cure if initiated early in life. For tuberous sclerosis complex (TSC), gene targets are showing strong promise for controlling seizures and other TSC manifestations.

It has also to be acknowledged that much of the ongoing expansion in knowledge taking place across diseases in pediatric neurology would have taken place with or without parent support. Dr. Bodensteiner singled out seizure disorders only as an illustration. “In the various forms of epilepsy, we now understand mechanisms in much greater detail than we did even a decade ago, let alone 30 years ago,” Dr. Bodensteiner said. In the context of the seizure medicines once widely employed on an empirical basis, “we now often have a clearer picture of why one drug works and not another.”
 

Growing pains: Child neurology evolves from a subspecialty to a specialty

Until about 10 years ago, child neurology was a subspecialty, variably placed within the departments of pediatrics or neurology based on institution. The decision to elevate child neurology to its own specialty solved some issues but created others, according to Dr. Bodensteiner.

“The initial problem was there was no immediate funding mechanism of residency slots and training,” Dr. Bodensteiner explained. The issue was particularly acute at smaller centers that had been able to support a subspecialty within another department but struggled with a new autonomous unit.

So far, the training requirements for specializing in child neurology remain largely unchanged. Clinical training requires 2 years of straight pediatrics, 1 year of adult neurology, 1 year of basic neurological science,” and 1 year of child neurology, but Dr. Bodensteiner said it might be time to reconsider. He pointed out that neurologists in general and child neurologists specifically are becoming increasingly focused in one area of expertise, such as epilepsy, neuromuscular diseases, and neurodevelopmental delay.

“It can be argued that a few months spent in a dementia clinic during training might not be the best use of time for a child neurologist working in congenital neurological diseases,” he said.

One consequence of the increasing degree of specialization in neurology overall, not just child neurology, has been the changes in recertification, according to Dr. Bodensteiner. Following a model used in other specialties, recertification in child neurology was initially based on an every-10-year examination. Ultimately, this was recognized as inconsistent with the target of keeping clinicians up to date.

“In general, I think that a lot of people waited for 9.5 years before cramming for an examination that was not necessarily relevant to the area in which they were working,” Dr. Bodensteiner said.

The revised process, carried out on an every-3-year cycle, involves board-guided review of the medical literature in 10 topic areas. Child neurologists can elect an article in any of the topic areas, but to complete their recertification process they must read articles in eight of these areas. Dr. Bodensteiner said that this approach has been more popular and is presumably more useful for staying abreast of developments.
 

Increased specialization necessitates collaboration

The radical increase in specialization in child neurology, like neurology in general, has been a necessary consequence of an avalanche of new information as advances in the field accelerate, but Dr. Bodensteiner cautioned that it is important for those working in these specialized areas to collaborate with others outside of their field of expertise.

“We cannot recognize what we do not know,” Dr. Bodensteiner said. If subspecialization within neurology is critical to stay current with rapid advances in very different diseases, then it also means that clinicians at every level, including within the field of child neurology, need to know when to collaborate or refer to ensure early diagnosis in challenging cases.

“Epileptologists have been trying for years to make it widely known that patients resistant to standard medications deserve referral, but I think this is increasingly true across domains,” Dr. Bodensteiner said. Neurology and child neurology are not alone, but the window of opportunity for effective intervention in children with a progressive disease might be particularly limited.

“The point is that this is more of a risk than it was 20 years ago,” said Dr. Bodensteiner, referring to the growth in new therapies. He cited data suggesting that a causative gene mutation can be identified in about 60% of rare diseases, which is a relatively new phenomenon. Of advances to improve outcomes, faster triage is becoming one of the most important in this increasingly specialized world.

With the growth in knowledge, “there is really no way to be an expert across all diseases in child neurology,” Dr. Bodensteiner said. “As physicians become increasingly insulated in their areas of expertise, I think there needs to be a greater emphasis on communication and collaboration.”

To some degree, this type of specialization has always existed, but Dr. Bodensteiner said the intensification of this trend is among the ways the field has most evolved over the past few decades. In inherited diseases that affect early child development, working together for a prompt diagnosis has assumed a new level of urgency.

For understanding the evolution in child neurology over the past 30 years, it would make sense to start with the science, particularly genetics, that have led to treatments and even cures for numerous inherited diseases over that time. When John Bodensteiner, MD, a pillar in the field of child neurology, was asked, he started with something different.

Parent advocacy accelerates advances in rare pediatric diseases

For the progress in many of the rare diseases seen by child neurologists in the last few decades, Dr. Bodensteiner first acknowledged parent support. “The concept was simple initially. For so many of these relatively rare diseases, like the Rett and Sturge-Weber syndromes, parents were learning of them for the first time. The support groups helped parents understand they were not alone. But it then evolved,” recalled Dr. Bodensteiner, who has been a professor of pediatrics and neurology at numerous institutions, most recently the Mayo Clinic in Rochester, Minn.

Many of these support groups first formed, or at least gained momentum, in the 1990s. “As the support groups grew, the members expanded their role to support research, in addition to supporting each other. They ended up volunteering their own data, providing more information about the epidemiology and disease course. They offered tissue samples for experimental studies. They enrolled their children in trials. And they raised funds,” Dr. Bodensteiner explained.

The impact of this advocacy has been enormous, according to Dr. Bodensteiner. As an expert in neuromuscular diseases, he worked directly with several of these groups.

Although the growth in parent advocacy took place in parallel with major advances in genetics that were driving new insights into disease pathophysiology, Dr. Bodensteiner characterized parent advocates as important partners in accelerating the transition of new information to clinical utility. He suggested that there is little doubt about the importance of their role in moving the science forward by drawing attention to rare disorders that had few, if any, treatment options at the time the advocacy groups were formed.

Since the 1990s, the list of childhood neurologic diseases for which there has been meaningful progress is long. Dr. Bodensteiner selected several examples. For Rett syndrome, key molecular mechanisms have now been isolated, providing meaningful targets that show potential for treatment. For spinal muscular atrophy (SMA), therapies have become available, one of which involves gene replacement that appears to provide cure if initiated early in life. For tuberous sclerosis complex (TSC), gene targets are showing strong promise for controlling seizures and other TSC manifestations.

It has also to be acknowledged that much of the ongoing expansion in knowledge taking place across diseases in pediatric neurology would have taken place with or without parent support. Dr. Bodensteiner singled out seizure disorders only as an illustration. “In the various forms of epilepsy, we now understand mechanisms in much greater detail than we did even a decade ago, let alone 30 years ago,” Dr. Bodensteiner said. In the context of the seizure medicines once widely employed on an empirical basis, “we now often have a clearer picture of why one drug works and not another.”
 

Growing pains: Child neurology evolves from a subspecialty to a specialty

Until about 10 years ago, child neurology was a subspecialty, variably placed within the departments of pediatrics or neurology based on institution. The decision to elevate child neurology to its own specialty solved some issues but created others, according to Dr. Bodensteiner.

“The initial problem was there was no immediate funding mechanism of residency slots and training,” Dr. Bodensteiner explained. The issue was particularly acute at smaller centers that had been able to support a subspecialty within another department but struggled with a new autonomous unit.

So far, the training requirements for specializing in child neurology remain largely unchanged. Clinical training requires 2 years of straight pediatrics, 1 year of adult neurology, 1 year of basic neurological science,” and 1 year of child neurology, but Dr. Bodensteiner said it might be time to reconsider. He pointed out that neurologists in general and child neurologists specifically are becoming increasingly focused in one area of expertise, such as epilepsy, neuromuscular diseases, and neurodevelopmental delay.

“It can be argued that a few months spent in a dementia clinic during training might not be the best use of time for a child neurologist working in congenital neurological diseases,” he said.

One consequence of the increasing degree of specialization in neurology overall, not just child neurology, has been the changes in recertification, according to Dr. Bodensteiner. Following a model used in other specialties, recertification in child neurology was initially based on an every-10-year examination. Ultimately, this was recognized as inconsistent with the target of keeping clinicians up to date.

“In general, I think that a lot of people waited for 9.5 years before cramming for an examination that was not necessarily relevant to the area in which they were working,” Dr. Bodensteiner said.

The revised process, carried out on an every-3-year cycle, involves board-guided review of the medical literature in 10 topic areas. Child neurologists can elect an article in any of the topic areas, but to complete their recertification process they must read articles in eight of these areas. Dr. Bodensteiner said that this approach has been more popular and is presumably more useful for staying abreast of developments.
 

Increased specialization necessitates collaboration

The radical increase in specialization in child neurology, like neurology in general, has been a necessary consequence of an avalanche of new information as advances in the field accelerate, but Dr. Bodensteiner cautioned that it is important for those working in these specialized areas to collaborate with others outside of their field of expertise.

“We cannot recognize what we do not know,” Dr. Bodensteiner said. If subspecialization within neurology is critical to stay current with rapid advances in very different diseases, then it also means that clinicians at every level, including within the field of child neurology, need to know when to collaborate or refer to ensure early diagnosis in challenging cases.

“Epileptologists have been trying for years to make it widely known that patients resistant to standard medications deserve referral, but I think this is increasingly true across domains,” Dr. Bodensteiner said. Neurology and child neurology are not alone, but the window of opportunity for effective intervention in children with a progressive disease might be particularly limited.

“The point is that this is more of a risk than it was 20 years ago,” said Dr. Bodensteiner, referring to the growth in new therapies. He cited data suggesting that a causative gene mutation can be identified in about 60% of rare diseases, which is a relatively new phenomenon. Of advances to improve outcomes, faster triage is becoming one of the most important in this increasingly specialized world.

With the growth in knowledge, “there is really no way to be an expert across all diseases in child neurology,” Dr. Bodensteiner said. “As physicians become increasingly insulated in their areas of expertise, I think there needs to be a greater emphasis on communication and collaboration.”

To some degree, this type of specialization has always existed, but Dr. Bodensteiner said the intensification of this trend is among the ways the field has most evolved over the past few decades. In inherited diseases that affect early child development, working together for a prompt diagnosis has assumed a new level of urgency.

For understanding the evolution in child neurology over the past 30 years, it would make sense to start with the science, particularly genetics, that have led to treatments and even cures for numerous inherited diseases over that time. When John Bodensteiner, MD, a pillar in the field of child neurology, was asked, he started with something different.

Parent advocacy accelerates advances in rare pediatric diseases

For the progress in many of the rare diseases seen by child neurologists in the last few decades, Dr. Bodensteiner first acknowledged parent support. “The concept was simple initially. For so many of these relatively rare diseases, like the Rett and Sturge-Weber syndromes, parents were learning of them for the first time. The support groups helped parents understand they were not alone. But it then evolved,” recalled Dr. Bodensteiner, who has been a professor of pediatrics and neurology at numerous institutions, most recently the Mayo Clinic in Rochester, Minn.

Many of these support groups first formed, or at least gained momentum, in the 1990s. “As the support groups grew, the members expanded their role to support research, in addition to supporting each other. They ended up volunteering their own data, providing more information about the epidemiology and disease course. They offered tissue samples for experimental studies. They enrolled their children in trials. And they raised funds,” Dr. Bodensteiner explained.

The impact of this advocacy has been enormous, according to Dr. Bodensteiner. As an expert in neuromuscular diseases, he worked directly with several of these groups.

Although the growth in parent advocacy took place in parallel with major advances in genetics that were driving new insights into disease pathophysiology, Dr. Bodensteiner characterized parent advocates as important partners in accelerating the transition of new information to clinical utility. He suggested that there is little doubt about the importance of their role in moving the science forward by drawing attention to rare disorders that had few, if any, treatment options at the time the advocacy groups were formed.

Since the 1990s, the list of childhood neurologic diseases for which there has been meaningful progress is long. Dr. Bodensteiner selected several examples. For Rett syndrome, key molecular mechanisms have now been isolated, providing meaningful targets that show potential for treatment. For spinal muscular atrophy (SMA), therapies have become available, one of which involves gene replacement that appears to provide cure if initiated early in life. For tuberous sclerosis complex (TSC), gene targets are showing strong promise for controlling seizures and other TSC manifestations.

It has also to be acknowledged that much of the ongoing expansion in knowledge taking place across diseases in pediatric neurology would have taken place with or without parent support. Dr. Bodensteiner singled out seizure disorders only as an illustration. “In the various forms of epilepsy, we now understand mechanisms in much greater detail than we did even a decade ago, let alone 30 years ago,” Dr. Bodensteiner said. In the context of the seizure medicines once widely employed on an empirical basis, “we now often have a clearer picture of why one drug works and not another.”
 

Growing pains: Child neurology evolves from a subspecialty to a specialty

Until about 10 years ago, child neurology was a subspecialty, variably placed within the departments of pediatrics or neurology based on institution. The decision to elevate child neurology to its own specialty solved some issues but created others, according to Dr. Bodensteiner.

“The initial problem was there was no immediate funding mechanism of residency slots and training,” Dr. Bodensteiner explained. The issue was particularly acute at smaller centers that had been able to support a subspecialty within another department but struggled with a new autonomous unit.

So far, the training requirements for specializing in child neurology remain largely unchanged. Clinical training requires 2 years of straight pediatrics, 1 year of adult neurology, 1 year of basic neurological science,” and 1 year of child neurology, but Dr. Bodensteiner said it might be time to reconsider. He pointed out that neurologists in general and child neurologists specifically are becoming increasingly focused in one area of expertise, such as epilepsy, neuromuscular diseases, and neurodevelopmental delay.

“It can be argued that a few months spent in a dementia clinic during training might not be the best use of time for a child neurologist working in congenital neurological diseases,” he said.

One consequence of the increasing degree of specialization in neurology overall, not just child neurology, has been the changes in recertification, according to Dr. Bodensteiner. Following a model used in other specialties, recertification in child neurology was initially based on an every-10-year examination. Ultimately, this was recognized as inconsistent with the target of keeping clinicians up to date.

“In general, I think that a lot of people waited for 9.5 years before cramming for an examination that was not necessarily relevant to the area in which they were working,” Dr. Bodensteiner said.

The revised process, carried out on an every-3-year cycle, involves board-guided review of the medical literature in 10 topic areas. Child neurologists can elect an article in any of the topic areas, but to complete their recertification process they must read articles in eight of these areas. Dr. Bodensteiner said that this approach has been more popular and is presumably more useful for staying abreast of developments.
 

Increased specialization necessitates collaboration

The radical increase in specialization in child neurology, like neurology in general, has been a necessary consequence of an avalanche of new information as advances in the field accelerate, but Dr. Bodensteiner cautioned that it is important for those working in these specialized areas to collaborate with others outside of their field of expertise.

“We cannot recognize what we do not know,” Dr. Bodensteiner said. If subspecialization within neurology is critical to stay current with rapid advances in very different diseases, then it also means that clinicians at every level, including within the field of child neurology, need to know when to collaborate or refer to ensure early diagnosis in challenging cases.

“Epileptologists have been trying for years to make it widely known that patients resistant to standard medications deserve referral, but I think this is increasingly true across domains,” Dr. Bodensteiner said. Neurology and child neurology are not alone, but the window of opportunity for effective intervention in children with a progressive disease might be particularly limited.

“The point is that this is more of a risk than it was 20 years ago,” said Dr. Bodensteiner, referring to the growth in new therapies. He cited data suggesting that a causative gene mutation can be identified in about 60% of rare diseases, which is a relatively new phenomenon. Of advances to improve outcomes, faster triage is becoming one of the most important in this increasingly specialized world.

With the growth in knowledge, “there is really no way to be an expert across all diseases in child neurology,” Dr. Bodensteiner said. “As physicians become increasingly insulated in their areas of expertise, I think there needs to be a greater emphasis on communication and collaboration.”

To some degree, this type of specialization has always existed, but Dr. Bodensteiner said the intensification of this trend is among the ways the field has most evolved over the past few decades. In inherited diseases that affect early child development, working together for a prompt diagnosis has assumed a new level of urgency.

Diets containing higher amounts of certain food categories appear to be protective against cardiovascular (CV) disease and premature death, suggests a new study with a broad international scope. Most of the protective food categories are in line with standard dietary guidelines for good health, but one that may be heart-protective is not usually included in such recommendations.

fcafotodigital/Getty Images

The food categories that were found to be protective include fruit, vegetables, nuts, legumes, and fish but also dairy, “mainly whole-fat,” in an analysis based on the international Prospective Urban and Rural Epidemiological (PURE) study and data from five other international trials that encompassed more than 240,000 people.

A healthy diet scoring system was derived from dietary patterns and clinical events observed in the PURE study and was applied to the populations of the other trials. Higher scores, corresponding to greater consumption of the six food categories, tracked with significantly reduced risks for death, myocardial infarction (MI), and stroke.

Reductions in mortality and CV-disease risk that were linked to the higher scores were especially pronounced in lower-income countries in the study published onlinein the European Heart Journal with lead author Andrew Mente, PhD, Population Health Research Institute, McMaster University, Hamilton, Ont.

The study in part refutes the frequent preference for low-fat or no-fat dairy foods over whole-fat dairy in healthy-diet recommendations. But it is consistent with earlier findings from PURE of reduced mortality risk with increased consumption of dietary fat, including saturated fat.

Whereas healthy-diet recommendations tend to emphasize reduced intake of fat, especially saturated fat, the report notes that “there are almost no national or international strategies and policies to increase a number of protective foods,” such as nuts, fish, and dairy.

“Therefore, while the findings from PURE are largely consistent with the nutrition science and modern dietary recommendations to focus on protective foods, the public’s understanding of healthy eating and relevant global policies have not yet caught up to this science,” it states.

“Guidelines and policy actions need to be updated with this newer evidence,” Dr. Mente said in an interview. “For example, the World Health Organization remains mainly focused on reducing certain nutrients, such as fat, saturated fat, added sugar, and salt,” he said. “These recommendations are echoed by government policy actions and industry, as evident by the continued focus on the usual nutrients in food labels of many countries.”

The current findings, Dr. Mente said, “can be used to ensure that the public’s understanding of healthy eating and relevant global policies are able to catch up to the science.”
 

Healthy diet score

PURE investigators developed their healthy diet score using data from 147,642 people from the general population in 21 countries. The investigators compared self-reported dietary intakes with long-term clinical outcomes.

The scoring system assigned a value of 1 for each of the six health-food categories when individuals’ intake exceeded the entire cohort’s median intake. It assigned a 0 when intake was below the median. The total PURE healthy diet score consisted of the sum of the six values, with higher scores corresponding to a healthier diet. The mean score for cohort was 2.95.

There were 15,707 deaths and 40,764 CV events during a median follow-up of 9.3 years. A score of at least 5 points, compared with 0 or 1 point, was associated with significantly reduced hazard ratios for mortality, MI, and stroke in multivariable analysis:

• Mortality: HR, 0.70 (95% CI, 0.63-0.77; P < .0001).
• Major CV disease: HR, 0.82 (95% CI, 0.75-0.91; P < .0001).
• MI: HR, 0.86 (95% CI, 0.75-0.99; P = .0014).
• Stroke: HR, 0.81 (95% CI, 0.71-0.93; P = .0034).

The healthy diet score’s relationship to clinical outcomes was explored in five other large independent studies, including three prospective trials of patients with CV disease that spanned 50 countries, a case-control study with MI patients in 52 countries, and a case-control study with stroke patients in 33 countries.

In the three prospective trials, higher scores were associated with reduced mortality, CV disease events, and MI:

• Mortality: HR, 0.73 (95% CI, 0.66-0.81).
• Major CV disease: HR, 0.79 (95% CI, 0.72-0.87).
• MI: HR, 0.85 (95% CI, 0.71-0.99).

In the two case-control studies, a higher diet score was associated with reduced odds ratios for first MI and for stroke:

• MI: OR, 0.72 (95% CI, 0.65-0.80).
• Stroke: OR, 0.57 (95% CI, 0.50-0.65).

In an analysis based on the PURE cohort, incorporation of unprocessed red meat or whole grains into the health diet score produced similar results, suggesting that a “modest amount” of meat or whole grains can be part of a healthy diet, the authors contend.

The results were similar in a combined analysis of all the prospective studies. In particular, improvement in diet score by one quintile was associated with significantly reduced risks for the following:

• Mortality: HR, 0.92 (95% CI, 0.90-0.93).
• Major CV disease: HR, 0.94 (95% CI, 0.93-0.95).
• MI: HR, 0.94 (95% CI, 0.92-0.96).
• Stroke: HR, 0.94 (95% CI, 0.89-0.99).
• Death or CV disease: HR, 0.93 (95% CI, 0.92-0.94).

“This strongly indicates that the take-home message for patients is the same as for general populations,” Dr. Mente said. “Eat plenty of fruits, vegetables, nuts, legumes, and a moderate amount of fish and whole-fat dairy to lower risk of CV disease and mortality.”

Dairy foods are not widely consumed in some cultures, he said, “but availability and cost are also factors in determining consumption.” Nonetheless, a high-quality diet can be achieved without including or excluding dairy foods. Context-specific policies and priorities are needed for different populations, “rather than a one-size-fits-all global policy.”

Food labels in many countries mainly focus on “reducing certain nutrients as the end-all, be-all,” Dr. Mente observed. “Our findings can be used as a basis for recommendations regarding what a healthy diet should be globally and then modified for each region based on the specific types of foods that are available and affordable in each region.”

Moreover, he said, “targeted food policies are needed to increase the availability and affordability of healthy foods, especially in lower-income countries where intakes are low.”
 

Common human biology

The current results from PURE “confirm prior observations from mostly Western nations that low intakes of fruits, vegetables, nuts, legumes, and fish are major risk factors for poor health,” observes Dariush Mozaffarian, MD, DrPH, MPH, Tufts University, Boston, in an accompanying editorial. “This suggests that common human biology, not merely confounding, explains these observed diet–disease relationships, strengthening causal inference on the power of nutrition.”

Moreover, “These findings provide further support that dairy foods, including whole-fat dairy, can be part of a healthy diet,” Dr. Mozaffarian writes. “The new results in PURE, in combination with prior reports, call for a re-evaluation of unrelenting guidelines to avoid whole-fat dairy products.”

Such studies “remind us of the continuing and devastating rise in diet-related chronic diseases globally, and of the power of protective foods to help address these burdens,” the editorial continues. “It is time for national nutrition guidelines, private sector innovations, government tax policy and agricultural incentives, food procurement policies, labeling and other regulatory priorities, and food-based health care interventions to catch up to the science.”
 

Not automatically superior

“I do not believe guidelines should be changed based on this single study,” contends Howard D. Sesso, ScD, MPH, associate director of the division of preventive medicine at Brigham and Women’s Hospital, Boston, who isn’t part of PURE. “But I welcome the scientific dialog that should come out of any study that challenges what we think we know,” he told this news organization.

“Many other dietary patterns have been identified over the years that also do a great job in predicting disease risk in observational studies,” observed Dr. Sesso. “Is PURE that much better? Maybe, maybe not. But not enough to dismiss other dietary patterns that are already the basis of dietary recommendations in the U.S., Europe, and worldwide.”

The PURE healthy diet score, he said, “appears to work well within the confines of their large pooling of studies around the world, but that doesn’t automatically make it superior to other dietary patterns.” The score “was only modestly, but not greatly, better than existing dietary patterns evaluated.”

Randomized controlled trials are needed, Dr. Sesso said, to “delve into more specific dietary components,” including unprocessed red meat, whole grains, and high-fat dairy foods. And, he said, more observational studies are needed to examine the score’s association with other cardiometabolic outcomes.

The PURE study is funded by the Population Health Research Institute, the Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario; with support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care; and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. Additional contributions are from Novartis and King Pharma. Dr. Mente, Dr. Mozaffarian, and Dr. Sesso have disclosed no relevant financial relationships.

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

Diets containing higher amounts of certain food categories appear to be protective against cardiovascular (CV) disease and premature death, suggests a new study with a broad international scope. Most of the protective food categories are in line with standard dietary guidelines for good health, but one that may be heart-protective is not usually included in such recommendations.

fcafotodigital/Getty Images

The food categories that were found to be protective include fruit, vegetables, nuts, legumes, and fish but also dairy, “mainly whole-fat,” in an analysis based on the international Prospective Urban and Rural Epidemiological (PURE) study and data from five other international trials that encompassed more than 240,000 people.

A healthy diet scoring system was derived from dietary patterns and clinical events observed in the PURE study and was applied to the populations of the other trials. Higher scores, corresponding to greater consumption of the six food categories, tracked with significantly reduced risks for death, myocardial infarction (MI), and stroke.

Reductions in mortality and CV-disease risk that were linked to the higher scores were especially pronounced in lower-income countries in the study published onlinein the European Heart Journal with lead author Andrew Mente, PhD, Population Health Research Institute, McMaster University, Hamilton, Ont.

The study in part refutes the frequent preference for low-fat or no-fat dairy foods over whole-fat dairy in healthy-diet recommendations. But it is consistent with earlier findings from PURE of reduced mortality risk with increased consumption of dietary fat, including saturated fat.

Whereas healthy-diet recommendations tend to emphasize reduced intake of fat, especially saturated fat, the report notes that “there are almost no national or international strategies and policies to increase a number of protective foods,” such as nuts, fish, and dairy.

“Therefore, while the findings from PURE are largely consistent with the nutrition science and modern dietary recommendations to focus on protective foods, the public’s understanding of healthy eating and relevant global policies have not yet caught up to this science,” it states.

“Guidelines and policy actions need to be updated with this newer evidence,” Dr. Mente said in an interview. “For example, the World Health Organization remains mainly focused on reducing certain nutrients, such as fat, saturated fat, added sugar, and salt,” he said. “These recommendations are echoed by government policy actions and industry, as evident by the continued focus on the usual nutrients in food labels of many countries.”

The current findings, Dr. Mente said, “can be used to ensure that the public’s understanding of healthy eating and relevant global policies are able to catch up to the science.”
 

Healthy diet score

PURE investigators developed their healthy diet score using data from 147,642 people from the general population in 21 countries. The investigators compared self-reported dietary intakes with long-term clinical outcomes.

The scoring system assigned a value of 1 for each of the six health-food categories when individuals’ intake exceeded the entire cohort’s median intake. It assigned a 0 when intake was below the median. The total PURE healthy diet score consisted of the sum of the six values, with higher scores corresponding to a healthier diet. The mean score for cohort was 2.95.

There were 15,707 deaths and 40,764 CV events during a median follow-up of 9.3 years. A score of at least 5 points, compared with 0 or 1 point, was associated with significantly reduced hazard ratios for mortality, MI, and stroke in multivariable analysis:

• Mortality: HR, 0.70 (95% CI, 0.63-0.77; P < .0001).
• Major CV disease: HR, 0.82 (95% CI, 0.75-0.91; P < .0001).
• MI: HR, 0.86 (95% CI, 0.75-0.99; P = .0014).
• Stroke: HR, 0.81 (95% CI, 0.71-0.93; P = .0034).

The healthy diet score’s relationship to clinical outcomes was explored in five other large independent studies, including three prospective trials of patients with CV disease that spanned 50 countries, a case-control study with MI patients in 52 countries, and a case-control study with stroke patients in 33 countries.

In the three prospective trials, higher scores were associated with reduced mortality, CV disease events, and MI:

• Mortality: HR, 0.73 (95% CI, 0.66-0.81).
• Major CV disease: HR, 0.79 (95% CI, 0.72-0.87).
• MI: HR, 0.85 (95% CI, 0.71-0.99).

In the two case-control studies, a higher diet score was associated with reduced odds ratios for first MI and for stroke:

• MI: OR, 0.72 (95% CI, 0.65-0.80).
• Stroke: OR, 0.57 (95% CI, 0.50-0.65).

In an analysis based on the PURE cohort, incorporation of unprocessed red meat or whole grains into the health diet score produced similar results, suggesting that a “modest amount” of meat or whole grains can be part of a healthy diet, the authors contend.

The results were similar in a combined analysis of all the prospective studies. In particular, improvement in diet score by one quintile was associated with significantly reduced risks for the following:

• Mortality: HR, 0.92 (95% CI, 0.90-0.93).
• Major CV disease: HR, 0.94 (95% CI, 0.93-0.95).
• MI: HR, 0.94 (95% CI, 0.92-0.96).
• Stroke: HR, 0.94 (95% CI, 0.89-0.99).
• Death or CV disease: HR, 0.93 (95% CI, 0.92-0.94).

“This strongly indicates that the take-home message for patients is the same as for general populations,” Dr. Mente said. “Eat plenty of fruits, vegetables, nuts, legumes, and a moderate amount of fish and whole-fat dairy to lower risk of CV disease and mortality.”

Dairy foods are not widely consumed in some cultures, he said, “but availability and cost are also factors in determining consumption.” Nonetheless, a high-quality diet can be achieved without including or excluding dairy foods. Context-specific policies and priorities are needed for different populations, “rather than a one-size-fits-all global policy.”

Food labels in many countries mainly focus on “reducing certain nutrients as the end-all, be-all,” Dr. Mente observed. “Our findings can be used as a basis for recommendations regarding what a healthy diet should be globally and then modified for each region based on the specific types of foods that are available and affordable in each region.”

Moreover, he said, “targeted food policies are needed to increase the availability and affordability of healthy foods, especially in lower-income countries where intakes are low.”
 

Common human biology

The current results from PURE “confirm prior observations from mostly Western nations that low intakes of fruits, vegetables, nuts, legumes, and fish are major risk factors for poor health,” observes Dariush Mozaffarian, MD, DrPH, MPH, Tufts University, Boston, in an accompanying editorial. “This suggests that common human biology, not merely confounding, explains these observed diet–disease relationships, strengthening causal inference on the power of nutrition.”

Moreover, “These findings provide further support that dairy foods, including whole-fat dairy, can be part of a healthy diet,” Dr. Mozaffarian writes. “The new results in PURE, in combination with prior reports, call for a re-evaluation of unrelenting guidelines to avoid whole-fat dairy products.”

Such studies “remind us of the continuing and devastating rise in diet-related chronic diseases globally, and of the power of protective foods to help address these burdens,” the editorial continues. “It is time for national nutrition guidelines, private sector innovations, government tax policy and agricultural incentives, food procurement policies, labeling and other regulatory priorities, and food-based health care interventions to catch up to the science.”
 

Not automatically superior

“I do not believe guidelines should be changed based on this single study,” contends Howard D. Sesso, ScD, MPH, associate director of the division of preventive medicine at Brigham and Women’s Hospital, Boston, who isn’t part of PURE. “But I welcome the scientific dialog that should come out of any study that challenges what we think we know,” he told this news organization.

“Many other dietary patterns have been identified over the years that also do a great job in predicting disease risk in observational studies,” observed Dr. Sesso. “Is PURE that much better? Maybe, maybe not. But not enough to dismiss other dietary patterns that are already the basis of dietary recommendations in the U.S., Europe, and worldwide.”

The PURE healthy diet score, he said, “appears to work well within the confines of their large pooling of studies around the world, but that doesn’t automatically make it superior to other dietary patterns.” The score “was only modestly, but not greatly, better than existing dietary patterns evaluated.”

Randomized controlled trials are needed, Dr. Sesso said, to “delve into more specific dietary components,” including unprocessed red meat, whole grains, and high-fat dairy foods. And, he said, more observational studies are needed to examine the score’s association with other cardiometabolic outcomes.

The PURE study is funded by the Population Health Research Institute, the Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario; with support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care; and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. Additional contributions are from Novartis and King Pharma. Dr. Mente, Dr. Mozaffarian, and Dr. Sesso have disclosed no relevant financial relationships.

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

Diets containing higher amounts of certain food categories appear to be protective against cardiovascular (CV) disease and premature death, suggests a new study with a broad international scope. Most of the protective food categories are in line with standard dietary guidelines for good health, but one that may be heart-protective is not usually included in such recommendations.

fcafotodigital/Getty Images

The food categories that were found to be protective include fruit, vegetables, nuts, legumes, and fish but also dairy, “mainly whole-fat,” in an analysis based on the international Prospective Urban and Rural Epidemiological (PURE) study and data from five other international trials that encompassed more than 240,000 people.

A healthy diet scoring system was derived from dietary patterns and clinical events observed in the PURE study and was applied to the populations of the other trials. Higher scores, corresponding to greater consumption of the six food categories, tracked with significantly reduced risks for death, myocardial infarction (MI), and stroke.

Reductions in mortality and CV-disease risk that were linked to the higher scores were especially pronounced in lower-income countries in the study published onlinein the European Heart Journal with lead author Andrew Mente, PhD, Population Health Research Institute, McMaster University, Hamilton, Ont.

The study in part refutes the frequent preference for low-fat or no-fat dairy foods over whole-fat dairy in healthy-diet recommendations. But it is consistent with earlier findings from PURE of reduced mortality risk with increased consumption of dietary fat, including saturated fat.

Whereas healthy-diet recommendations tend to emphasize reduced intake of fat, especially saturated fat, the report notes that “there are almost no national or international strategies and policies to increase a number of protective foods,” such as nuts, fish, and dairy.

“Therefore, while the findings from PURE are largely consistent with the nutrition science and modern dietary recommendations to focus on protective foods, the public’s understanding of healthy eating and relevant global policies have not yet caught up to this science,” it states.

“Guidelines and policy actions need to be updated with this newer evidence,” Dr. Mente said in an interview. “For example, the World Health Organization remains mainly focused on reducing certain nutrients, such as fat, saturated fat, added sugar, and salt,” he said. “These recommendations are echoed by government policy actions and industry, as evident by the continued focus on the usual nutrients in food labels of many countries.”

The current findings, Dr. Mente said, “can be used to ensure that the public’s understanding of healthy eating and relevant global policies are able to catch up to the science.”
 

Healthy diet score

PURE investigators developed their healthy diet score using data from 147,642 people from the general population in 21 countries. The investigators compared self-reported dietary intakes with long-term clinical outcomes.

The scoring system assigned a value of 1 for each of the six health-food categories when individuals’ intake exceeded the entire cohort’s median intake. It assigned a 0 when intake was below the median. The total PURE healthy diet score consisted of the sum of the six values, with higher scores corresponding to a healthier diet. The mean score for cohort was 2.95.

There were 15,707 deaths and 40,764 CV events during a median follow-up of 9.3 years. A score of at least 5 points, compared with 0 or 1 point, was associated with significantly reduced hazard ratios for mortality, MI, and stroke in multivariable analysis:

• Mortality: HR, 0.70 (95% CI, 0.63-0.77; P < .0001).
• Major CV disease: HR, 0.82 (95% CI, 0.75-0.91; P < .0001).
• MI: HR, 0.86 (95% CI, 0.75-0.99; P = .0014).
• Stroke: HR, 0.81 (95% CI, 0.71-0.93; P = .0034).

The healthy diet score’s relationship to clinical outcomes was explored in five other large independent studies, including three prospective trials of patients with CV disease that spanned 50 countries, a case-control study with MI patients in 52 countries, and a case-control study with stroke patients in 33 countries.

In the three prospective trials, higher scores were associated with reduced mortality, CV disease events, and MI:

• Mortality: HR, 0.73 (95% CI, 0.66-0.81).
• Major CV disease: HR, 0.79 (95% CI, 0.72-0.87).
• MI: HR, 0.85 (95% CI, 0.71-0.99).

In the two case-control studies, a higher diet score was associated with reduced odds ratios for first MI and for stroke:

• MI: OR, 0.72 (95% CI, 0.65-0.80).
• Stroke: OR, 0.57 (95% CI, 0.50-0.65).

In an analysis based on the PURE cohort, incorporation of unprocessed red meat or whole grains into the health diet score produced similar results, suggesting that a “modest amount” of meat or whole grains can be part of a healthy diet, the authors contend.

The results were similar in a combined analysis of all the prospective studies. In particular, improvement in diet score by one quintile was associated with significantly reduced risks for the following:

• Mortality: HR, 0.92 (95% CI, 0.90-0.93).
• Major CV disease: HR, 0.94 (95% CI, 0.93-0.95).
• MI: HR, 0.94 (95% CI, 0.92-0.96).
• Stroke: HR, 0.94 (95% CI, 0.89-0.99).
• Death or CV disease: HR, 0.93 (95% CI, 0.92-0.94).

“This strongly indicates that the take-home message for patients is the same as for general populations,” Dr. Mente said. “Eat plenty of fruits, vegetables, nuts, legumes, and a moderate amount of fish and whole-fat dairy to lower risk of CV disease and mortality.”

Dairy foods are not widely consumed in some cultures, he said, “but availability and cost are also factors in determining consumption.” Nonetheless, a high-quality diet can be achieved without including or excluding dairy foods. Context-specific policies and priorities are needed for different populations, “rather than a one-size-fits-all global policy.”

Food labels in many countries mainly focus on “reducing certain nutrients as the end-all, be-all,” Dr. Mente observed. “Our findings can be used as a basis for recommendations regarding what a healthy diet should be globally and then modified for each region based on the specific types of foods that are available and affordable in each region.”

Moreover, he said, “targeted food policies are needed to increase the availability and affordability of healthy foods, especially in lower-income countries where intakes are low.”
 

Common human biology

The current results from PURE “confirm prior observations from mostly Western nations that low intakes of fruits, vegetables, nuts, legumes, and fish are major risk factors for poor health,” observes Dariush Mozaffarian, MD, DrPH, MPH, Tufts University, Boston, in an accompanying editorial. “This suggests that common human biology, not merely confounding, explains these observed diet–disease relationships, strengthening causal inference on the power of nutrition.”

Moreover, “These findings provide further support that dairy foods, including whole-fat dairy, can be part of a healthy diet,” Dr. Mozaffarian writes. “The new results in PURE, in combination with prior reports, call for a re-evaluation of unrelenting guidelines to avoid whole-fat dairy products.”

Such studies “remind us of the continuing and devastating rise in diet-related chronic diseases globally, and of the power of protective foods to help address these burdens,” the editorial continues. “It is time for national nutrition guidelines, private sector innovations, government tax policy and agricultural incentives, food procurement policies, labeling and other regulatory priorities, and food-based health care interventions to catch up to the science.”
 

Not automatically superior

“I do not believe guidelines should be changed based on this single study,” contends Howard D. Sesso, ScD, MPH, associate director of the division of preventive medicine at Brigham and Women’s Hospital, Boston, who isn’t part of PURE. “But I welcome the scientific dialog that should come out of any study that challenges what we think we know,” he told this news organization.

“Many other dietary patterns have been identified over the years that also do a great job in predicting disease risk in observational studies,” observed Dr. Sesso. “Is PURE that much better? Maybe, maybe not. But not enough to dismiss other dietary patterns that are already the basis of dietary recommendations in the U.S., Europe, and worldwide.”

The PURE healthy diet score, he said, “appears to work well within the confines of their large pooling of studies around the world, but that doesn’t automatically make it superior to other dietary patterns.” The score “was only modestly, but not greatly, better than existing dietary patterns evaluated.”

Randomized controlled trials are needed, Dr. Sesso said, to “delve into more specific dietary components,” including unprocessed red meat, whole grains, and high-fat dairy foods. And, he said, more observational studies are needed to examine the score’s association with other cardiometabolic outcomes.

The PURE study is funded by the Population Health Research Institute, the Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario; with support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care; and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. Additional contributions are from Novartis and King Pharma. Dr. Mente, Dr. Mozaffarian, and Dr. Sesso have disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved a labeling update for the injectable LDL cholesterol–lowering agent inclisiran (Leqvio) that expands its indications to include primary prevention for patients with elevated LDL cholesterol, Novartis has announced.

The first-in-class small interfering RNA (siRNA) agent was approved in 2021 as an adjunct to statins for patients with clinical cardiovascular disease or heterozygous familial hypercholesterolemia. The indications now include patients taking statins for primary dyslipidemia who have high-risk comorbidities such as diabetes but who do not have a history of cardiovascular events, the company said.

Inclisiran, with a mechanism of action unique among drugs for dyslipidemia, works by “silencing” RNA involved in the synthesis of proprotein convertase subtilisin/kexin type 9. The protein helps regulate the number of LDL cholesterol cell-surface receptors.

Novartis said it has “global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”

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

The Food and Drug Administration has approved a labeling update for the injectable LDL cholesterol–lowering agent inclisiran (Leqvio) that expands its indications to include primary prevention for patients with elevated LDL cholesterol, Novartis has announced.

The first-in-class small interfering RNA (siRNA) agent was approved in 2021 as an adjunct to statins for patients with clinical cardiovascular disease or heterozygous familial hypercholesterolemia. The indications now include patients taking statins for primary dyslipidemia who have high-risk comorbidities such as diabetes but who do not have a history of cardiovascular events, the company said.

Inclisiran, with a mechanism of action unique among drugs for dyslipidemia, works by “silencing” RNA involved in the synthesis of proprotein convertase subtilisin/kexin type 9. The protein helps regulate the number of LDL cholesterol cell-surface receptors.

Novartis said it has “global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”

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

The Food and Drug Administration has approved a labeling update for the injectable LDL cholesterol–lowering agent inclisiran (Leqvio) that expands its indications to include primary prevention for patients with elevated LDL cholesterol, Novartis has announced.

The first-in-class small interfering RNA (siRNA) agent was approved in 2021 as an adjunct to statins for patients with clinical cardiovascular disease or heterozygous familial hypercholesterolemia. The indications now include patients taking statins for primary dyslipidemia who have high-risk comorbidities such as diabetes but who do not have a history of cardiovascular events, the company said.

Inclisiran, with a mechanism of action unique among drugs for dyslipidemia, works by “silencing” RNA involved in the synthesis of proprotein convertase subtilisin/kexin type 9. The protein helps regulate the number of LDL cholesterol cell-surface receptors.

Novartis said it has “global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”

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

SINGAPORE – When injected subcutaneously, the interleukin-36 receptor antagonist spesolimab significantly reduced the risk for generalized pustular psoriasis (GPP) flares, according to results of a study presented in a late-breaker session at the World Congress of Dermatology,

In the phase 2b study, patients who received the high-dose regimen (a 600-mg subcutaneous loading dose, then 300-mg SC every 4 weeks) of spesolimab experienced 84% fewer GPP fares over 48 weeks, compared with those on placebo, reported Bruce Strober, MD, PhD, Central Connecticut Dermatology, Cromwell, and clinical professor of dermatology, Yale University, New Haven, Conn. “Additionally, no flares occurred after week 4, and this, in turn, translated into improved patient outcomes.”

GPP is a rare, chronic, systemic neutrophilic skin disease. The resulting flares, characterized by painful pustules all over the body, can lead to sepsis, shock, and other life-threatening complications. “People who have it are considerably burdened by it, so targeted therapy of this disease is incredibly important because it leads to lessened morbidity and, importantly, mortality for these patients,” Dr. Strober said.

“It’s important not only to treat the flares but also to prevent them,” he noted.

The intravenous formulation of spesolimab (Spevigo) was approved for the treatment of GPP flares in adults by the Food and Drug Administration in September 2022. It is now authorized in nearly 40 countries, including Japan, China, and the European Union.

The phase 2 Effisayil 2 study presented at the meeting evaluated the subcutaneous formulation of spesolimab. Data on subcutaneous spesolimab has been submitted to the FDA, and has received breakthrough therapy designation, according to the manufacturer, Boehringer Ingelheim.

Flare prevention

In the study, 123 patients with GPP were randomly assigned 1:1:1:1 to one of four groups: high-dose spesolimab, medium-dose (600-mg SC loading dose, then 300-mg SC every 12 weeks), low-dose (300-mg SC loading dose, then 150-mg SC every 12 weeks), or placebo. In the event of a flare during the randomized treatment period, a patient was administered a single, 900-mg intravenous dose of spesolimab.

Nearly two-thirds of the participants were female and nearly two-thirds were Asian, with a mean age of about 39-43 years.

The mean numbers of GPP flares experienced annually by those in the low-, medium-, and high-dose spesolimab groups were 2.7, 1.9, and 2.4, respectively (2.4% in the placebo group). Fewer than a third had concurrent plaque psoriasis at baseline. Most (48.4%-63.3%) did not have an IL-36RN mutation.

Additionally, the Generalized Pustular Psoriasis Physician Global Assessment total score was 1 in 74.2%-93.5% of participants, and 0 in the remainder.

The primary study endpoint was the time to GPP flare by week 48. The risk of developing a flare among those on high-dose spesolimab was 84% lower, compared with that of those on placebo (hazard ratio, 0.16; 95% confidence interval, 0.05-0.54; P = .0005). No patients on the high dose had a flare after the 4th week of the study.

Similarly, for the secondary endpoint (occurrence of at least one GPP flare by week 48). Dr. Strober and his colleagues reported that high-dose spesolimab was superior to placebo with a risk difference of -39% (95% CI, –0.62 to –0.16; P = .0013). By contrast, the risk differences for the medium- and low-dose spesolimab arms were –0.23 (95% CI, –0.46 to 0.01) and -0.31 (95% CI, –0.54 to –0.08), respectively.

The safety profile of subcutaneous spesolimab across all three doses was similar to that of placebo, and there was no dose-dependent trend. Reported adverse events (AEs) were mild. There were five (5.4%) AEs leading to discontinuation of the drug in the medium- and high-dose groups, but none in the low-dose group. Overall, there were nine (9.7%) serious AEs reported in the spesolimab groups, and three (10%) in the high-dose group; no deaths occurred on any dose.

Participants most often reported injection-site erythema, reported in 13 (14%) of the patients on spesolimab versus 1 (3.3%) of those on placebo.

“Overall, the study demonstrates that subcutaneous spesolimab is effective at controlling GPP flares, especially at a high dose relative to placebo, and supports subcutaneous spesolimab for the therapy for GPP flare prevention,” Dr. Strober said at the meeting.
 

Targeting the IL-36 pathway

In a comment, Todd Schlesinger, MD, Clinical Research Center of the Carolinas, Charleston, S.C., who moderated the session, said: “It’s very exciting to be able to have a subcutaneous version of the medication.”

“I think the IL-36 is a great pathway,” he said, referring to the signaling pathway within the immune system that is central to the pathogenesis of GPP and several other autoinflammatory diseases.

However, Dr. Schlesinger said that he would have liked to have seen data on how many patients ended up treated with intravenous spesolimab.

He added that he would like future studies of subcutaneous spesolimab to examine the effect in different populations that vary by parameters such as weight, race, and disease severity. “Just seeing how somebody who’s flaring five times a year and you give them this medication and they’re now flaring once a year – that’s interesting data that we might like to know in the future.”

Other than for preventing GPP flares, spesolimab is being studied for treating other IL-36–mediated skin diseases, such as palmoplantar pustulosis.

The study was funded by Boehringer Ingelheim; both Dr. Strober and Dr. Schlesinger do research and consulting for BI, and receive funding from multiple other pharmaceutical companies.

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

SINGAPORE – When injected subcutaneously, the interleukin-36 receptor antagonist spesolimab significantly reduced the risk for generalized pustular psoriasis (GPP) flares, according to results of a study presented in a late-breaker session at the World Congress of Dermatology,

In the phase 2b study, patients who received the high-dose regimen (a 600-mg subcutaneous loading dose, then 300-mg SC every 4 weeks) of spesolimab experienced 84% fewer GPP fares over 48 weeks, compared with those on placebo, reported Bruce Strober, MD, PhD, Central Connecticut Dermatology, Cromwell, and clinical professor of dermatology, Yale University, New Haven, Conn. “Additionally, no flares occurred after week 4, and this, in turn, translated into improved patient outcomes.”

GPP is a rare, chronic, systemic neutrophilic skin disease. The resulting flares, characterized by painful pustules all over the body, can lead to sepsis, shock, and other life-threatening complications. “People who have it are considerably burdened by it, so targeted therapy of this disease is incredibly important because it leads to lessened morbidity and, importantly, mortality for these patients,” Dr. Strober said.

“It’s important not only to treat the flares but also to prevent them,” he noted.

The intravenous formulation of spesolimab (Spevigo) was approved for the treatment of GPP flares in adults by the Food and Drug Administration in September 2022. It is now authorized in nearly 40 countries, including Japan, China, and the European Union.

The phase 2 Effisayil 2 study presented at the meeting evaluated the subcutaneous formulation of spesolimab. Data on subcutaneous spesolimab has been submitted to the FDA, and has received breakthrough therapy designation, according to the manufacturer, Boehringer Ingelheim.

Flare prevention

In the study, 123 patients with GPP were randomly assigned 1:1:1:1 to one of four groups: high-dose spesolimab, medium-dose (600-mg SC loading dose, then 300-mg SC every 12 weeks), low-dose (300-mg SC loading dose, then 150-mg SC every 12 weeks), or placebo. In the event of a flare during the randomized treatment period, a patient was administered a single, 900-mg intravenous dose of spesolimab.

Nearly two-thirds of the participants were female and nearly two-thirds were Asian, with a mean age of about 39-43 years.

The mean numbers of GPP flares experienced annually by those in the low-, medium-, and high-dose spesolimab groups were 2.7, 1.9, and 2.4, respectively (2.4% in the placebo group). Fewer than a third had concurrent plaque psoriasis at baseline. Most (48.4%-63.3%) did not have an IL-36RN mutation.

Additionally, the Generalized Pustular Psoriasis Physician Global Assessment total score was 1 in 74.2%-93.5% of participants, and 0 in the remainder.

The primary study endpoint was the time to GPP flare by week 48. The risk of developing a flare among those on high-dose spesolimab was 84% lower, compared with that of those on placebo (hazard ratio, 0.16; 95% confidence interval, 0.05-0.54; P = .0005). No patients on the high dose had a flare after the 4th week of the study.

Similarly, for the secondary endpoint (occurrence of at least one GPP flare by week 48). Dr. Strober and his colleagues reported that high-dose spesolimab was superior to placebo with a risk difference of -39% (95% CI, –0.62 to –0.16; P = .0013). By contrast, the risk differences for the medium- and low-dose spesolimab arms were –0.23 (95% CI, –0.46 to 0.01) and -0.31 (95% CI, –0.54 to –0.08), respectively.

The safety profile of subcutaneous spesolimab across all three doses was similar to that of placebo, and there was no dose-dependent trend. Reported adverse events (AEs) were mild. There were five (5.4%) AEs leading to discontinuation of the drug in the medium- and high-dose groups, but none in the low-dose group. Overall, there were nine (9.7%) serious AEs reported in the spesolimab groups, and three (10%) in the high-dose group; no deaths occurred on any dose.

Participants most often reported injection-site erythema, reported in 13 (14%) of the patients on spesolimab versus 1 (3.3%) of those on placebo.

“Overall, the study demonstrates that subcutaneous spesolimab is effective at controlling GPP flares, especially at a high dose relative to placebo, and supports subcutaneous spesolimab for the therapy for GPP flare prevention,” Dr. Strober said at the meeting.
 

Targeting the IL-36 pathway

In a comment, Todd Schlesinger, MD, Clinical Research Center of the Carolinas, Charleston, S.C., who moderated the session, said: “It’s very exciting to be able to have a subcutaneous version of the medication.”

“I think the IL-36 is a great pathway,” he said, referring to the signaling pathway within the immune system that is central to the pathogenesis of GPP and several other autoinflammatory diseases.

However, Dr. Schlesinger said that he would have liked to have seen data on how many patients ended up treated with intravenous spesolimab.

He added that he would like future studies of subcutaneous spesolimab to examine the effect in different populations that vary by parameters such as weight, race, and disease severity. “Just seeing how somebody who’s flaring five times a year and you give them this medication and they’re now flaring once a year – that’s interesting data that we might like to know in the future.”

Other than for preventing GPP flares, spesolimab is being studied for treating other IL-36–mediated skin diseases, such as palmoplantar pustulosis.

The study was funded by Boehringer Ingelheim; both Dr. Strober and Dr. Schlesinger do research and consulting for BI, and receive funding from multiple other pharmaceutical companies.

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

SINGAPORE – When injected subcutaneously, the interleukin-36 receptor antagonist spesolimab significantly reduced the risk for generalized pustular psoriasis (GPP) flares, according to results of a study presented in a late-breaker session at the World Congress of Dermatology,

In the phase 2b study, patients who received the high-dose regimen (a 600-mg subcutaneous loading dose, then 300-mg SC every 4 weeks) of spesolimab experienced 84% fewer GPP fares over 48 weeks, compared with those on placebo, reported Bruce Strober, MD, PhD, Central Connecticut Dermatology, Cromwell, and clinical professor of dermatology, Yale University, New Haven, Conn. “Additionally, no flares occurred after week 4, and this, in turn, translated into improved patient outcomes.”

GPP is a rare, chronic, systemic neutrophilic skin disease. The resulting flares, characterized by painful pustules all over the body, can lead to sepsis, shock, and other life-threatening complications. “People who have it are considerably burdened by it, so targeted therapy of this disease is incredibly important because it leads to lessened morbidity and, importantly, mortality for these patients,” Dr. Strober said.

“It’s important not only to treat the flares but also to prevent them,” he noted.

The intravenous formulation of spesolimab (Spevigo) was approved for the treatment of GPP flares in adults by the Food and Drug Administration in September 2022. It is now authorized in nearly 40 countries, including Japan, China, and the European Union.

The phase 2 Effisayil 2 study presented at the meeting evaluated the subcutaneous formulation of spesolimab. Data on subcutaneous spesolimab has been submitted to the FDA, and has received breakthrough therapy designation, according to the manufacturer, Boehringer Ingelheim.

Flare prevention

In the study, 123 patients with GPP were randomly assigned 1:1:1:1 to one of four groups: high-dose spesolimab, medium-dose (600-mg SC loading dose, then 300-mg SC every 12 weeks), low-dose (300-mg SC loading dose, then 150-mg SC every 12 weeks), or placebo. In the event of a flare during the randomized treatment period, a patient was administered a single, 900-mg intravenous dose of spesolimab.

Nearly two-thirds of the participants were female and nearly two-thirds were Asian, with a mean age of about 39-43 years.

The mean numbers of GPP flares experienced annually by those in the low-, medium-, and high-dose spesolimab groups were 2.7, 1.9, and 2.4, respectively (2.4% in the placebo group). Fewer than a third had concurrent plaque psoriasis at baseline. Most (48.4%-63.3%) did not have an IL-36RN mutation.

Additionally, the Generalized Pustular Psoriasis Physician Global Assessment total score was 1 in 74.2%-93.5% of participants, and 0 in the remainder.

The primary study endpoint was the time to GPP flare by week 48. The risk of developing a flare among those on high-dose spesolimab was 84% lower, compared with that of those on placebo (hazard ratio, 0.16; 95% confidence interval, 0.05-0.54; P = .0005). No patients on the high dose had a flare after the 4th week of the study.

Similarly, for the secondary endpoint (occurrence of at least one GPP flare by week 48). Dr. Strober and his colleagues reported that high-dose spesolimab was superior to placebo with a risk difference of -39% (95% CI, –0.62 to –0.16; P = .0013). By contrast, the risk differences for the medium- and low-dose spesolimab arms were –0.23 (95% CI, –0.46 to 0.01) and -0.31 (95% CI, –0.54 to –0.08), respectively.

The safety profile of subcutaneous spesolimab across all three doses was similar to that of placebo, and there was no dose-dependent trend. Reported adverse events (AEs) were mild. There were five (5.4%) AEs leading to discontinuation of the drug in the medium- and high-dose groups, but none in the low-dose group. Overall, there were nine (9.7%) serious AEs reported in the spesolimab groups, and three (10%) in the high-dose group; no deaths occurred on any dose.

Participants most often reported injection-site erythema, reported in 13 (14%) of the patients on spesolimab versus 1 (3.3%) of those on placebo.

“Overall, the study demonstrates that subcutaneous spesolimab is effective at controlling GPP flares, especially at a high dose relative to placebo, and supports subcutaneous spesolimab for the therapy for GPP flare prevention,” Dr. Strober said at the meeting.
 

Targeting the IL-36 pathway

In a comment, Todd Schlesinger, MD, Clinical Research Center of the Carolinas, Charleston, S.C., who moderated the session, said: “It’s very exciting to be able to have a subcutaneous version of the medication.”

“I think the IL-36 is a great pathway,” he said, referring to the signaling pathway within the immune system that is central to the pathogenesis of GPP and several other autoinflammatory diseases.

However, Dr. Schlesinger said that he would have liked to have seen data on how many patients ended up treated with intravenous spesolimab.

He added that he would like future studies of subcutaneous spesolimab to examine the effect in different populations that vary by parameters such as weight, race, and disease severity. “Just seeing how somebody who’s flaring five times a year and you give them this medication and they’re now flaring once a year – that’s interesting data that we might like to know in the future.”

Other than for preventing GPP flares, spesolimab is being studied for treating other IL-36–mediated skin diseases, such as palmoplantar pustulosis.

The study was funded by Boehringer Ingelheim; both Dr. Strober and Dr. Schlesinger do research and consulting for BI, and receive funding from multiple other pharmaceutical companies.

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

This transcript has been edited for clarity.

Hi. I’m Art Caplan, PhD. I’m director of the division of medical ethics at the New York University Grossman School of Medicine.

Every once in a while at my school, I get referrals about interesting or difficult clinical cases where doctors would like some input or advice that they can consider in managing a patient. Sometimes those requests come from other hospitals to me. I’ve been doing that kind of ethics consulting, both as a member of various ethics committees and sometimes individually, when, for various reasons, doctors don’t want to go to the Ethics Committee as a first stop.

There was a very interesting case recently involving a young woman I’m going to call Tinslee. She was 17 years old and she suffered, sadly, from recurrent metastatic osteogenic sarcoma. She had bone cancer. It had first been diagnosed at the age of 9. She had received chemotherapy and been under that treatment for a while.

If osteosarcoma is treated before it spreads outside the area where it began, the 5-year survival rate for people like her is about 75%. If the cancer spreads outside of the bones and gets into surrounding tissues, organs, or – worse – into the lymph nodes and starts traveling around, the 5-year survival rate drops to about 60%. The two approaches are chemotherapy and amputation. That’s what we have to offer patients like Tinslee.

Initially, her chemotherapy worked. She went to school and enjoyed sports. She was a real fan of softball and tried to manage the team and be involved. At the time I learned about her, she was planning to go to college. Her love of softball remained, but given the recurrence of the cancer, she had no chance to pursue her athletic interests, not only as a player, but also as a manager or even as a coach for younger players. That was all off the table.

She’d been very compliant up until this time with her chemotherapy. When the recommendation came in that she undergo nonstandard chemotherapy because of the reoccurrence, with experimental drugs using an experimental protocol, she said to her family and the doctors that she didn’t want to do it. She would rather die. She couldn’t take any more chemotherapy and she certainly didn’t want to do it if it was experimental, with the outcomes of this intervention being uncertain.

Her dad said, “She can’t decide. She’s a minor. She’s only 17. I want you to do it – administer this novel form of chemotherapy and try to save her.” Her mother said, “Her input matters. I want to listen to her.” Her mom wasn’t as adamant about doing it or not, but she really felt that Tinslee should be heard loudly because she felt she was mature enough or old enough, even though a minor, to really have a position about what it is to undergo chemotherapy.

Time matters in trying to control the spread, and the doctors were pushing for experimental intervention. I should add, by the way, that although it didn’t really drive the decision about whether to do it or not do it, experimental care like this is not covered by most insurance, and it wasn’t covered by their insurance, so they were facing a big bill if the experimental intervention was administered.

There was some money in a grant to cover some of it, but they were going to face some big financial costs. It never came up in my discussions with the doctors about what to do. I’m not sure whether it ever came up with the family’s discussion with the doctors about what to do, or even whether Tinslee was worrying and didn’t want her family to face a financial burden.

I suggested that we bring the family in. We did some counseling. We had a social worker and we brought in a pastor because these people were fairly religious. We talked about all scenarios, including accepting death, knowing that this disease was not likely to go into remission with the experimental effort; maybe it would, but the doctors were not optimistic.

We tried to talk about how much we should listen to what this young woman wanted. We knew there was the possibility of going to court and having a judge decide this, but in my experience, I do not like going to judges and courts because I know what they’re going to say. They almost always say “administer the intervention.” They don’t want to be in a position of saying don’t do something. They’re a little less willing to do that if something is experimental, but generally speaking, if you’re headed to court, it’s because you’ve decided that you want this to happen.

I felt, in all honesty, that this young woman should have some real respect of her position because the treatment was experimental. She is approaching the age of competency and consent, and she’s been through many interventions. She knows what’s involved. I think you really have to listen hard to what she’s saying.

By the way, after this case, I looked and there have been some surveys of residents in pediatrics. A large number of them said that they hadn’t received any training about what to do when mature minors refuse experimental treatments. The study I saw said that 30% had not undergone any training about this, so we certainly want to introduce that into the appropriate areas of medicine and talk about this with residents and fellows.

Long story short, we had the family meeting, we had another meeting with dad and mom and Tinslee, and the dad began to come around and he began to listen hard. Tinslee said what she wanted was to go to her prom. She wanted to get to her sister’s junior high school softball championship game. If you will, setting some smaller goals that seemed to make her very, very happy began to satisfy mom and dad and they could accept her refusal.

Ultimately, an agreement was reached that she would not undergo the experimental intervention. We agreed on a course of palliative care, recommended that as what the doctors follow, and they decided to do so. Sadly, Tinslee died. She died at home. She did make it to her prom.

I think the outcome, while difficult, sad, tragic, and a close call, was correct. Mature minors who have been through a rough life of interventions and know the price to pay – and for those who have recurrent disease and now face only experimental options – if they say no, that’s something we really have to listen to very hard.



Dr. Kaplan is director, division of medical ethics, New York University Langone Medical Center, New York. He reported a conflict of interest with Johnson & Johnson’s Panel for Compassionate Drug Use.
 

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

This transcript has been edited for clarity.

Hi. I’m Art Caplan, PhD. I’m director of the division of medical ethics at the New York University Grossman School of Medicine.

Every once in a while at my school, I get referrals about interesting or difficult clinical cases where doctors would like some input or advice that they can consider in managing a patient. Sometimes those requests come from other hospitals to me. I’ve been doing that kind of ethics consulting, both as a member of various ethics committees and sometimes individually, when, for various reasons, doctors don’t want to go to the Ethics Committee as a first stop.

There was a very interesting case recently involving a young woman I’m going to call Tinslee. She was 17 years old and she suffered, sadly, from recurrent metastatic osteogenic sarcoma. She had bone cancer. It had first been diagnosed at the age of 9. She had received chemotherapy and been under that treatment for a while.

If osteosarcoma is treated before it spreads outside the area where it began, the 5-year survival rate for people like her is about 75%. If the cancer spreads outside of the bones and gets into surrounding tissues, organs, or – worse – into the lymph nodes and starts traveling around, the 5-year survival rate drops to about 60%. The two approaches are chemotherapy and amputation. That’s what we have to offer patients like Tinslee.

Initially, her chemotherapy worked. She went to school and enjoyed sports. She was a real fan of softball and tried to manage the team and be involved. At the time I learned about her, she was planning to go to college. Her love of softball remained, but given the recurrence of the cancer, she had no chance to pursue her athletic interests, not only as a player, but also as a manager or even as a coach for younger players. That was all off the table.

She’d been very compliant up until this time with her chemotherapy. When the recommendation came in that she undergo nonstandard chemotherapy because of the reoccurrence, with experimental drugs using an experimental protocol, she said to her family and the doctors that she didn’t want to do it. She would rather die. She couldn’t take any more chemotherapy and she certainly didn’t want to do it if it was experimental, with the outcomes of this intervention being uncertain.

Her dad said, “She can’t decide. She’s a minor. She’s only 17. I want you to do it – administer this novel form of chemotherapy and try to save her.” Her mother said, “Her input matters. I want to listen to her.” Her mom wasn’t as adamant about doing it or not, but she really felt that Tinslee should be heard loudly because she felt she was mature enough or old enough, even though a minor, to really have a position about what it is to undergo chemotherapy.

Time matters in trying to control the spread, and the doctors were pushing for experimental intervention. I should add, by the way, that although it didn’t really drive the decision about whether to do it or not do it, experimental care like this is not covered by most insurance, and it wasn’t covered by their insurance, so they were facing a big bill if the experimental intervention was administered.

There was some money in a grant to cover some of it, but they were going to face some big financial costs. It never came up in my discussions with the doctors about what to do. I’m not sure whether it ever came up with the family’s discussion with the doctors about what to do, or even whether Tinslee was worrying and didn’t want her family to face a financial burden.

I suggested that we bring the family in. We did some counseling. We had a social worker and we brought in a pastor because these people were fairly religious. We talked about all scenarios, including accepting death, knowing that this disease was not likely to go into remission with the experimental effort; maybe it would, but the doctors were not optimistic.

We tried to talk about how much we should listen to what this young woman wanted. We knew there was the possibility of going to court and having a judge decide this, but in my experience, I do not like going to judges and courts because I know what they’re going to say. They almost always say “administer the intervention.” They don’t want to be in a position of saying don’t do something. They’re a little less willing to do that if something is experimental, but generally speaking, if you’re headed to court, it’s because you’ve decided that you want this to happen.

I felt, in all honesty, that this young woman should have some real respect of her position because the treatment was experimental. She is approaching the age of competency and consent, and she’s been through many interventions. She knows what’s involved. I think you really have to listen hard to what she’s saying.

By the way, after this case, I looked and there have been some surveys of residents in pediatrics. A large number of them said that they hadn’t received any training about what to do when mature minors refuse experimental treatments. The study I saw said that 30% had not undergone any training about this, so we certainly want to introduce that into the appropriate areas of medicine and talk about this with residents and fellows.

Long story short, we had the family meeting, we had another meeting with dad and mom and Tinslee, and the dad began to come around and he began to listen hard. Tinslee said what she wanted was to go to her prom. She wanted to get to her sister’s junior high school softball championship game. If you will, setting some smaller goals that seemed to make her very, very happy began to satisfy mom and dad and they could accept her refusal.

Ultimately, an agreement was reached that she would not undergo the experimental intervention. We agreed on a course of palliative care, recommended that as what the doctors follow, and they decided to do so. Sadly, Tinslee died. She died at home. She did make it to her prom.

I think the outcome, while difficult, sad, tragic, and a close call, was correct. Mature minors who have been through a rough life of interventions and know the price to pay – and for those who have recurrent disease and now face only experimental options – if they say no, that’s something we really have to listen to very hard.



Dr. Kaplan is director, division of medical ethics, New York University Langone Medical Center, New York. He reported a conflict of interest with Johnson & Johnson’s Panel for Compassionate Drug Use.
 

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

This transcript has been edited for clarity.

Hi. I’m Art Caplan, PhD. I’m director of the division of medical ethics at the New York University Grossman School of Medicine.

Every once in a while at my school, I get referrals about interesting or difficult clinical cases where doctors would like some input or advice that they can consider in managing a patient. Sometimes those requests come from other hospitals to me. I’ve been doing that kind of ethics consulting, both as a member of various ethics committees and sometimes individually, when, for various reasons, doctors don’t want to go to the Ethics Committee as a first stop.

There was a very interesting case recently involving a young woman I’m going to call Tinslee. She was 17 years old and she suffered, sadly, from recurrent metastatic osteogenic sarcoma. She had bone cancer. It had first been diagnosed at the age of 9. She had received chemotherapy and been under that treatment for a while.

If osteosarcoma is treated before it spreads outside the area where it began, the 5-year survival rate for people like her is about 75%. If the cancer spreads outside of the bones and gets into surrounding tissues, organs, or – worse – into the lymph nodes and starts traveling around, the 5-year survival rate drops to about 60%. The two approaches are chemotherapy and amputation. That’s what we have to offer patients like Tinslee.

Initially, her chemotherapy worked. She went to school and enjoyed sports. She was a real fan of softball and tried to manage the team and be involved. At the time I learned about her, she was planning to go to college. Her love of softball remained, but given the recurrence of the cancer, she had no chance to pursue her athletic interests, not only as a player, but also as a manager or even as a coach for younger players. That was all off the table.

She’d been very compliant up until this time with her chemotherapy. When the recommendation came in that she undergo nonstandard chemotherapy because of the reoccurrence, with experimental drugs using an experimental protocol, she said to her family and the doctors that she didn’t want to do it. She would rather die. She couldn’t take any more chemotherapy and she certainly didn’t want to do it if it was experimental, with the outcomes of this intervention being uncertain.

Her dad said, “She can’t decide. She’s a minor. She’s only 17. I want you to do it – administer this novel form of chemotherapy and try to save her.” Her mother said, “Her input matters. I want to listen to her.” Her mom wasn’t as adamant about doing it or not, but she really felt that Tinslee should be heard loudly because she felt she was mature enough or old enough, even though a minor, to really have a position about what it is to undergo chemotherapy.

Time matters in trying to control the spread, and the doctors were pushing for experimental intervention. I should add, by the way, that although it didn’t really drive the decision about whether to do it or not do it, experimental care like this is not covered by most insurance, and it wasn’t covered by their insurance, so they were facing a big bill if the experimental intervention was administered.

There was some money in a grant to cover some of it, but they were going to face some big financial costs. It never came up in my discussions with the doctors about what to do. I’m not sure whether it ever came up with the family’s discussion with the doctors about what to do, or even whether Tinslee was worrying and didn’t want her family to face a financial burden.

I suggested that we bring the family in. We did some counseling. We had a social worker and we brought in a pastor because these people were fairly religious. We talked about all scenarios, including accepting death, knowing that this disease was not likely to go into remission with the experimental effort; maybe it would, but the doctors were not optimistic.

We tried to talk about how much we should listen to what this young woman wanted. We knew there was the possibility of going to court and having a judge decide this, but in my experience, I do not like going to judges and courts because I know what they’re going to say. They almost always say “administer the intervention.” They don’t want to be in a position of saying don’t do something. They’re a little less willing to do that if something is experimental, but generally speaking, if you’re headed to court, it’s because you’ve decided that you want this to happen.

I felt, in all honesty, that this young woman should have some real respect of her position because the treatment was experimental. She is approaching the age of competency and consent, and she’s been through many interventions. She knows what’s involved. I think you really have to listen hard to what she’s saying.

By the way, after this case, I looked and there have been some surveys of residents in pediatrics. A large number of them said that they hadn’t received any training about what to do when mature minors refuse experimental treatments. The study I saw said that 30% had not undergone any training about this, so we certainly want to introduce that into the appropriate areas of medicine and talk about this with residents and fellows.

Long story short, we had the family meeting, we had another meeting with dad and mom and Tinslee, and the dad began to come around and he began to listen hard. Tinslee said what she wanted was to go to her prom. She wanted to get to her sister’s junior high school softball championship game. If you will, setting some smaller goals that seemed to make her very, very happy began to satisfy mom and dad and they could accept her refusal.

Ultimately, an agreement was reached that she would not undergo the experimental intervention. We agreed on a course of palliative care, recommended that as what the doctors follow, and they decided to do so. Sadly, Tinslee died. She died at home. She did make it to her prom.

I think the outcome, while difficult, sad, tragic, and a close call, was correct. Mature minors who have been through a rough life of interventions and know the price to pay – and for those who have recurrent disease and now face only experimental options – if they say no, that’s something we really have to listen to very hard.



Dr. Kaplan is director, division of medical ethics, New York University Langone Medical Center, New York. He reported a conflict of interest with Johnson & Johnson’s Panel for Compassionate Drug Use.
 

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

Scientists have developed a biodegradable implant that helps chemotherapy drugs penetrate the blood-brain barrier in mice and deliver a direct hit on brain tumors.

It’s the latest advance in a rapidly growing field using ultrasound – high-frequency sound waves undetectable to humans – to fight cancer and other diseases.

The problem addressed by the researchers is the blood-brain barrier, a nearly impenetrable blood vessel lining that keeps harmful molecules from passing into the brain from the blood. But this lining can also block chemo drugs from reaching cancer cells.

So the scientists implanted 1-cm² devices into the skulls of mice, directly behind the tumor site. The implants generate ultrasound waves, loosening the barrier and allowing the drugs to reach the tumor. The sound waves leave healthy tissue undamaged.

“You inject the drug into the body and turn on the ultrasound at the same time. You’re going to hit precisely at the tumor area every single time you use it,” said lead study author Thanh Nguyen, PhD, an associate professor of mechanical engineering at the University of Connecticut, Storrs.

The drug used in the study was paclitaxel, which normally struggles to get through the blood-brain barrier. The tumors shrank, and the mice doubled their lifetime, compared with untreated mice. The mice showed no bad health effects 6 months later. 
 

Breaking through the blood-brain barrier 

The biodegradable implant is made of glycine, an amino acid that’s also strongly piezoelectric, meaning it vibrates when subjected to an electrical current. To make it, researchers cultivated glycine crystals, shattered them into pieces, and finally used a process called electrospinning, which applies a high electrical voltage to the nanocrystals. 

Voltage flows to the implant via an external device. The resulting ultrasound causes the tightly adhered cells of the blood-brain barrier to vibrate, stretching them out and creating space for pores to form. 

“That allows in very tiny particles, including chemo drugs,” said Dr. Nguyen. 

His earlier biodegradable implant broke apart from the force, but the new glycine implant is more flexible, stable, and highly piezoelectric. It could be implanted after a patient has surgery to remove a brain tumor, to continue treating residual cancer cells. The implant dissolves harmlessly in the body over time, and doctors can control its lifespan. 
 

A new wave of uses for ultrasound 

Dr. Nguyen’s study builds on similar efforts, including a recent clinical trial of a nonbiodegradable implant for treating brain tumors. Ultrasound can focus energy on precise targets in the body.

It’s like “using a magnifying glass to focus multiple beams of light on a point and burn a hole in a leaf,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. This approach spares adjacent normal tissue.  

Doctors now understand more than 30 ways that ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. A decade ago, only five such interactions were known.

This opens the door for treating “a wide spectrum of medical disorders,” from neurodegenerative diseases like Alzheimer’s and Parkinson’s to difficult-to-treat cancers of the prostate and pancreas, and even addiction, said Dr. Kassell. 

Dr. Kassell envisions using focused ultrasound to treat brain tumors as an alternative (or complement) to surgery, chemotherapy, immunotherapy, or radiation therapy. In the meantime, implants have helped show “the effectiveness of opening the blood-brain barrier.”

Dr. Nguyen’s team plans on testing the safety and efficacy of their implant in pigs next. Eventually, Dr. Nguyen hopes to develop a patch with an array of implants to target different areas of the brain. 

One study coauthor is cofounder of PiezoBioMembrane and SingleTimeMicroneedles. The other study authors reported no conflicts of interest.

A version of this article originally appeared on WebMD.com.

Scientists have developed a biodegradable implant that helps chemotherapy drugs penetrate the blood-brain barrier in mice and deliver a direct hit on brain tumors.

It’s the latest advance in a rapidly growing field using ultrasound – high-frequency sound waves undetectable to humans – to fight cancer and other diseases.

The problem addressed by the researchers is the blood-brain barrier, a nearly impenetrable blood vessel lining that keeps harmful molecules from passing into the brain from the blood. But this lining can also block chemo drugs from reaching cancer cells.

So the scientists implanted 1-cm² devices into the skulls of mice, directly behind the tumor site. The implants generate ultrasound waves, loosening the barrier and allowing the drugs to reach the tumor. The sound waves leave healthy tissue undamaged.

“You inject the drug into the body and turn on the ultrasound at the same time. You’re going to hit precisely at the tumor area every single time you use it,” said lead study author Thanh Nguyen, PhD, an associate professor of mechanical engineering at the University of Connecticut, Storrs.

The drug used in the study was paclitaxel, which normally struggles to get through the blood-brain barrier. The tumors shrank, and the mice doubled their lifetime, compared with untreated mice. The mice showed no bad health effects 6 months later. 
 

Breaking through the blood-brain barrier 

The biodegradable implant is made of glycine, an amino acid that’s also strongly piezoelectric, meaning it vibrates when subjected to an electrical current. To make it, researchers cultivated glycine crystals, shattered them into pieces, and finally used a process called electrospinning, which applies a high electrical voltage to the nanocrystals. 

Voltage flows to the implant via an external device. The resulting ultrasound causes the tightly adhered cells of the blood-brain barrier to vibrate, stretching them out and creating space for pores to form. 

“That allows in very tiny particles, including chemo drugs,” said Dr. Nguyen. 

His earlier biodegradable implant broke apart from the force, but the new glycine implant is more flexible, stable, and highly piezoelectric. It could be implanted after a patient has surgery to remove a brain tumor, to continue treating residual cancer cells. The implant dissolves harmlessly in the body over time, and doctors can control its lifespan. 
 

A new wave of uses for ultrasound 

Dr. Nguyen’s study builds on similar efforts, including a recent clinical trial of a nonbiodegradable implant for treating brain tumors. Ultrasound can focus energy on precise targets in the body.

It’s like “using a magnifying glass to focus multiple beams of light on a point and burn a hole in a leaf,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. This approach spares adjacent normal tissue.  

Doctors now understand more than 30 ways that ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. A decade ago, only five such interactions were known.

This opens the door for treating “a wide spectrum of medical disorders,” from neurodegenerative diseases like Alzheimer’s and Parkinson’s to difficult-to-treat cancers of the prostate and pancreas, and even addiction, said Dr. Kassell. 

Dr. Kassell envisions using focused ultrasound to treat brain tumors as an alternative (or complement) to surgery, chemotherapy, immunotherapy, or radiation therapy. In the meantime, implants have helped show “the effectiveness of opening the blood-brain barrier.”

Dr. Nguyen’s team plans on testing the safety and efficacy of their implant in pigs next. Eventually, Dr. Nguyen hopes to develop a patch with an array of implants to target different areas of the brain. 

One study coauthor is cofounder of PiezoBioMembrane and SingleTimeMicroneedles. The other study authors reported no conflicts of interest.

A version of this article originally appeared on WebMD.com.

Scientists have developed a biodegradable implant that helps chemotherapy drugs penetrate the blood-brain barrier in mice and deliver a direct hit on brain tumors.

It’s the latest advance in a rapidly growing field using ultrasound – high-frequency sound waves undetectable to humans – to fight cancer and other diseases.

The problem addressed by the researchers is the blood-brain barrier, a nearly impenetrable blood vessel lining that keeps harmful molecules from passing into the brain from the blood. But this lining can also block chemo drugs from reaching cancer cells.

So the scientists implanted 1-cm² devices into the skulls of mice, directly behind the tumor site. The implants generate ultrasound waves, loosening the barrier and allowing the drugs to reach the tumor. The sound waves leave healthy tissue undamaged.

“You inject the drug into the body and turn on the ultrasound at the same time. You’re going to hit precisely at the tumor area every single time you use it,” said lead study author Thanh Nguyen, PhD, an associate professor of mechanical engineering at the University of Connecticut, Storrs.

The drug used in the study was paclitaxel, which normally struggles to get through the blood-brain barrier. The tumors shrank, and the mice doubled their lifetime, compared with untreated mice. The mice showed no bad health effects 6 months later. 
 

Breaking through the blood-brain barrier 

The biodegradable implant is made of glycine, an amino acid that’s also strongly piezoelectric, meaning it vibrates when subjected to an electrical current. To make it, researchers cultivated glycine crystals, shattered them into pieces, and finally used a process called electrospinning, which applies a high electrical voltage to the nanocrystals. 

Voltage flows to the implant via an external device. The resulting ultrasound causes the tightly adhered cells of the blood-brain barrier to vibrate, stretching them out and creating space for pores to form. 

“That allows in very tiny particles, including chemo drugs,” said Dr. Nguyen. 

His earlier biodegradable implant broke apart from the force, but the new glycine implant is more flexible, stable, and highly piezoelectric. It could be implanted after a patient has surgery to remove a brain tumor, to continue treating residual cancer cells. The implant dissolves harmlessly in the body over time, and doctors can control its lifespan. 
 

A new wave of uses for ultrasound 

Dr. Nguyen’s study builds on similar efforts, including a recent clinical trial of a nonbiodegradable implant for treating brain tumors. Ultrasound can focus energy on precise targets in the body.

It’s like “using a magnifying glass to focus multiple beams of light on a point and burn a hole in a leaf,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. This approach spares adjacent normal tissue.  

Doctors now understand more than 30 ways that ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. A decade ago, only five such interactions were known.

This opens the door for treating “a wide spectrum of medical disorders,” from neurodegenerative diseases like Alzheimer’s and Parkinson’s to difficult-to-treat cancers of the prostate and pancreas, and even addiction, said Dr. Kassell. 

Dr. Kassell envisions using focused ultrasound to treat brain tumors as an alternative (or complement) to surgery, chemotherapy, immunotherapy, or radiation therapy. In the meantime, implants have helped show “the effectiveness of opening the blood-brain barrier.”

Dr. Nguyen’s team plans on testing the safety and efficacy of their implant in pigs next. Eventually, Dr. Nguyen hopes to develop a patch with an array of implants to target different areas of the brain. 

One study coauthor is cofounder of PiezoBioMembrane and SingleTimeMicroneedles. The other study authors reported no conflicts of interest.

A version of this article originally appeared on WebMD.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study.

Basically, all cancers are caused by a mix of genetic and environmental factors, with some cancers driven more strongly by one or the other. When it comes to ovarian cancer, which kills more than 13,000 women per year in the United States, genetic factors like the BRCA gene mutations are well described.

Other risk factors, like early menarche and nulliparity, are difficult to modify. The only slam-dunk environmental toxin to be linked to ovarian cancer is asbestos. Still, the vast majority of women who develop ovarian cancer do not have a known high-risk gene or asbestos exposure, so other triggers may be out there. How do we find them? The answer may just be good old-fashioned epidemiology.

When you’re looking for a new culprit agent that causes a relatively rare disease, the case-control study design is your best friend.

That’s just what researchers, led by Anita Koushik at the University of Montreal, did in a new study appearing in the journal Occupational and Environmental Medicine.

They identified 497 women in Montreal who had recently been diagnosed with ovarian cancer. They then matched those women to 897 women without ovarian cancer, based on age and address. (This approach would not work well in the United States, as diagnosis of ovarian cancer might depend on access to medical care, which is not universal here. In Canada, however, it’s safer to assume that anyone who could have gotten ovarian cancer in Montreal would have been detected.)

Cases and controls identified, the researchers took a detailed occupational history for each participant: every job they ever worked, and when, and for how long. Each occupation was mapped to a standardized set of industries and, interestingly, to a set of environmental exposures ranging from cosmetic talc to cooking fumes to cotton dust, in what is known as a job-exposure matrix. Of course, they also collected data on other ovarian cancer risk factors.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.

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

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study.

Basically, all cancers are caused by a mix of genetic and environmental factors, with some cancers driven more strongly by one or the other. When it comes to ovarian cancer, which kills more than 13,000 women per year in the United States, genetic factors like the BRCA gene mutations are well described.

Other risk factors, like early menarche and nulliparity, are difficult to modify. The only slam-dunk environmental toxin to be linked to ovarian cancer is asbestos. Still, the vast majority of women who develop ovarian cancer do not have a known high-risk gene or asbestos exposure, so other triggers may be out there. How do we find them? The answer may just be good old-fashioned epidemiology.

When you’re looking for a new culprit agent that causes a relatively rare disease, the case-control study design is your best friend.

That’s just what researchers, led by Anita Koushik at the University of Montreal, did in a new study appearing in the journal Occupational and Environmental Medicine.

They identified 497 women in Montreal who had recently been diagnosed with ovarian cancer. They then matched those women to 897 women without ovarian cancer, based on age and address. (This approach would not work well in the United States, as diagnosis of ovarian cancer might depend on access to medical care, which is not universal here. In Canada, however, it’s safer to assume that anyone who could have gotten ovarian cancer in Montreal would have been detected.)

Cases and controls identified, the researchers took a detailed occupational history for each participant: every job they ever worked, and when, and for how long. Each occupation was mapped to a standardized set of industries and, interestingly, to a set of environmental exposures ranging from cosmetic talc to cooking fumes to cotton dust, in what is known as a job-exposure matrix. Of course, they also collected data on other ovarian cancer risk factors.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.

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

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study.

Basically, all cancers are caused by a mix of genetic and environmental factors, with some cancers driven more strongly by one or the other. When it comes to ovarian cancer, which kills more than 13,000 women per year in the United States, genetic factors like the BRCA gene mutations are well described.

Other risk factors, like early menarche and nulliparity, are difficult to modify. The only slam-dunk environmental toxin to be linked to ovarian cancer is asbestos. Still, the vast majority of women who develop ovarian cancer do not have a known high-risk gene or asbestos exposure, so other triggers may be out there. How do we find them? The answer may just be good old-fashioned epidemiology.

When you’re looking for a new culprit agent that causes a relatively rare disease, the case-control study design is your best friend.

That’s just what researchers, led by Anita Koushik at the University of Montreal, did in a new study appearing in the journal Occupational and Environmental Medicine.

They identified 497 women in Montreal who had recently been diagnosed with ovarian cancer. They then matched those women to 897 women without ovarian cancer, based on age and address. (This approach would not work well in the United States, as diagnosis of ovarian cancer might depend on access to medical care, which is not universal here. In Canada, however, it’s safer to assume that anyone who could have gotten ovarian cancer in Montreal would have been detected.)

Cases and controls identified, the researchers took a detailed occupational history for each participant: every job they ever worked, and when, and for how long. Each occupation was mapped to a standardized set of industries and, interestingly, to a set of environmental exposures ranging from cosmetic talc to cooking fumes to cotton dust, in what is known as a job-exposure matrix. Of course, they also collected data on other ovarian cancer risk factors.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.

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

Well-demarcated symmetrical scaly plaques and dactylitis are consistent with psoriasis and psoriatic arthritis (PsA). Even in the absence of significant skin disease, a patient like this should be evaluated by Rheumatology for initiation of disease-modifying antirheumatic drugs (DMARDs).

Psoriatic arthritis manifests as a peripheral arthritis affecting the small joints of the wrists and hands, pain at the insertion of tendons and ligaments (enthesitis), or as axial arthritis. This variable presentation and the lack of specific serological marker can make diagnosis challenging. Associated symptoms beyond the musculoskeletal system include uveitis, inflammatory bowel disease, and cutaneous psoriasis.¹ In contrast to osteoarthritis, PsA symptoms are often worse in the morning and improve over the course of the day. Patients with a history of psoriasis on the skin have about a 10% chance of developing PsA, with increased rates in patients who have more widespread plaques and patients with psoriasis at a young age.² Although not pathognomonic for PsA, pitting of the fingernails may reflect episodic enthesitis in the extensor tendons of the fingers.³ Radiographs of the hands in severe cases may demonstrate narrowing of the proximal portion of the distal or proximal interphalangeal joints with a cup-like concavity of the distal half of the joint.

Conventional DMARDs (such as methotrexate and azathioprine) and biologic DMARDs (including TNF-alpha inhibitors, IL-17 inhibitors, IL-23 inhibitors) are first-line treatments and can stop or slow the progression of disease but will not reverse existing damage. For this reason, it is important to promptly start DMARD therapy after the diagnosis has been established.⁴

This patient was initiated on adalimumab 40 mg subcutaneously every other week. Her pain improved after 2 months of therapy and her skin plaques almost entirely resolved at 6 months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Well-demarcated symmetrical scaly plaques and dactylitis are consistent with psoriasis and psoriatic arthritis (PsA). Even in the absence of significant skin disease, a patient like this should be evaluated by Rheumatology for initiation of disease-modifying antirheumatic drugs (DMARDs).

Psoriatic arthritis manifests as a peripheral arthritis affecting the small joints of the wrists and hands, pain at the insertion of tendons and ligaments (enthesitis), or as axial arthritis. This variable presentation and the lack of specific serological marker can make diagnosis challenging. Associated symptoms beyond the musculoskeletal system include uveitis, inflammatory bowel disease, and cutaneous psoriasis.¹ In contrast to osteoarthritis, PsA symptoms are often worse in the morning and improve over the course of the day. Patients with a history of psoriasis on the skin have about a 10% chance of developing PsA, with increased rates in patients who have more widespread plaques and patients with psoriasis at a young age.² Although not pathognomonic for PsA, pitting of the fingernails may reflect episodic enthesitis in the extensor tendons of the fingers.³ Radiographs of the hands in severe cases may demonstrate narrowing of the proximal portion of the distal or proximal interphalangeal joints with a cup-like concavity of the distal half of the joint.

Conventional DMARDs (such as methotrexate and azathioprine) and biologic DMARDs (including TNF-alpha inhibitors, IL-17 inhibitors, IL-23 inhibitors) are first-line treatments and can stop or slow the progression of disease but will not reverse existing damage. For this reason, it is important to promptly start DMARD therapy after the diagnosis has been established.⁴

This patient was initiated on adalimumab 40 mg subcutaneously every other week. Her pain improved after 2 months of therapy and her skin plaques almost entirely resolved at 6 months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Well-demarcated symmetrical scaly plaques and dactylitis are consistent with psoriasis and psoriatic arthritis (PsA). Even in the absence of significant skin disease, a patient like this should be evaluated by Rheumatology for initiation of disease-modifying antirheumatic drugs (DMARDs).

Psoriatic arthritis manifests as a peripheral arthritis affecting the small joints of the wrists and hands, pain at the insertion of tendons and ligaments (enthesitis), or as axial arthritis. This variable presentation and the lack of specific serological marker can make diagnosis challenging. Associated symptoms beyond the musculoskeletal system include uveitis, inflammatory bowel disease, and cutaneous psoriasis.¹ In contrast to osteoarthritis, PsA symptoms are often worse in the morning and improve over the course of the day. Patients with a history of psoriasis on the skin have about a 10% chance of developing PsA, with increased rates in patients who have more widespread plaques and patients with psoriasis at a young age.² Although not pathognomonic for PsA, pitting of the fingernails may reflect episodic enthesitis in the extensor tendons of the fingers.³ Radiographs of the hands in severe cases may demonstrate narrowing of the proximal portion of the distal or proximal interphalangeal joints with a cup-like concavity of the distal half of the joint.

Conventional DMARDs (such as methotrexate and azathioprine) and biologic DMARDs (including TNF-alpha inhibitors, IL-17 inhibitors, IL-23 inhibitors) are first-line treatments and can stop or slow the progression of disease but will not reverse existing damage. For this reason, it is important to promptly start DMARD therapy after the diagnosis has been established.⁴

This patient was initiated on adalimumab 40 mg subcutaneously every other week. Her pain improved after 2 months of therapy and her skin plaques almost entirely resolved at 6 months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

ILLUSTRATION: PAUL ZWOLAK

“If you don’t have a seat at the table, you are probably on the menu.” I first heard this quote in 2013, and it launched my interest in health care leadership and influenced me countless times over the last 10 years.

As Chief of Staff at Cleveland Clinic, I oversee nearly 5,000 physicians and scientists across the globe. I am involved in the physician life cycle: recruiting, hiring, privileging and credentialing, talent development, promotion, professionalism, and career transitions. I also sit at the intersection of medical care and the business of medicine. This means leading 18 clinical service lines responsible for 5.6 million visits, 161,000 surgeries, and billions of dollars in operating revenue per year. How I spend most of my time is a far cry from what I spent 11 years’ training to do—gynecologic surgery. This shift in my career was not because I changed my mind about caring for patients or that I tired of being a full-time surgeon. Nothing could be further from the truth. Women’s health remains my “why,” and my leadership journey has taught me that it is critical to have a seat at the table for the sake of ObGyns and women everywhere.

Women’s health on the menu

I will start with a concrete example of when we, as women and ObGyns, were on the menu. In late 2019, the Ohio state House of Representatives introduced a bill that subjected doctors to potential murder charges if they did not try everything to save the life of a mother and fetus, “including attempting to reimplant an ectopic pregnancy into the woman’s uterus.”¹ This bill was based on 2 case reports—one from 1915 and one from 1980—which were both low quality, and the latter case was deemed to be fraudulent.² How did this happen?

An Ohio state representative developed the bill with help from a lobbyist and without input from physicians or content experts. When asked, the representative shared that “he never researched whether re-implanting an ectopic pregnancy into a woman’s uterus was a viable medical procedure before including it in the bill.”³ He added, “I heard about it over the years. I never questioned it or gave it a lot of thought.”³

This example resonates deeply with many of us; it inspires us to speak up and act. As ObGyns, we clearly understand the consequences of legal and regulatory change in women’s health and how it directly impacts our patients and each of us as physicians. Let’s shift to something that you may feel less passion about, but I believe is equally important. This is where obstetrician-gynecologists sit in the intersection of medical care and business. This is the space where I spend most of my time, and from this vantage point, I worry about our field.

The business of medicine

Starting at the macroeconomic level, let’s think about how we as physicians are reimbursed and who makes these decisions. Looking at the national health care expenditure data, Medicare and Medicaid spending makes up nearly 40% of the total spend, and it is growing.⁴ Additionally, private health insurance tends to follow Centers for Medicare and Medicaid Services (CMS) decision making, further compounding its influence.⁴ In simple terms, CMS decides what is covered and how much we are paid. Whether you are in a solo private practice, an employer health care organization, or an academic medical center, physician reimbursement is declining.

In fact, Congress passed its year-end omnibus legislation in the final days of 2022, including a 2% Medicare physician payment cut for 2023,⁵ at a time when expenses to practice medicine, including nonphysician staff and supplies, are at an all-time high and we are living in a 6% inflationary state. This translates into being asked to serve more patients and cut costs. Our day-to-day feels much tighter, and this is why: Medicare physician pay increased just 11% over the past 20 years⁶ (2001–2021) in comparison to the cost of running a medical practice, which increased nearly 40% during that time. In other words, adjusting for inflation in practice costs, Medicare physician payment has fallen 22% over the last 20 years.⁷

Depending on your employment model, you may feel insulated from these changes as increases in reimbursement have occurred in other areas, such as hospitals and ambulatory surgery centers.⁸ In the short term, these increases help, as organizations will see additional funds. But there are 2 main issues: First, it is not nearly enough when you consider the soaring costs of running a hospital. And second, looking at our national population, we rely tremendously on self-employed doctors to serve our patients.

More than 80% of US counties lack adequate health care infrastructure.⁹ More than a third of the US population has less-than-adequate access to pharmacies, primary care physicians, hospitals, trauma centers, and low-cost health centers.⁹ To put things into perspective, more than 20% of counties in the United States are hospital deserts, where most people must drive more than 30 minutes to reach the closest hospital.⁹

There is good reason for this. Operating a hospital is a challenging endeavor. Even before the COVID-19 pandemic and the most recent health care financial challenges, most health care systems and large hospitals operated with very low operating margins (2%–3%). Businesses with similar margins include grocery stores and car dealerships. These low-margin businesses, including health care, rely on high volume for sustainability. High patient volumes distribute expensive hospital costs over many encounters. If physicians cannot sustain practices across the country, it is challenging to have sufficient admission and surgical volumes to justify the cost base of hospitals.

To tie this together, we have very little influence on what we are paid for our services. Reimbursement is declining, which makes it hard to have financially sustainable practices. As hospitals struggle, there is more pressure to prioritize highly profitable service lines, like orthopedics and urology, which are associated with favorable technical revenue. As hospitals are threatened, health care deserts widen, which leaves our entire health care system in jeopardy. Not surprisingly, this most likely affects those who face additional barriers to access, such as those with lower income, limited internet access, and lack of insurance. Together, these barriers further widen disparities in health care outcomes, including outcomes for women. Additionally, this death by a thousand cuts has eroded morale and increased physician burnout.

Transforming how we practice medicine is the only viable solution. I have good news: You are the leaders you have been waiting for.

Continue to: Physicians make good managers...

Physicians make good managers

To successfully transform how we practice medicine, it is critical that those leading the transformation deeply understand how medicine is practiced. The level of understanding required can be achieved only through years of medical practice, as a doctor. We understand how medical teams interact and that different sectors of our health care system are interdependent. Also, because physicians drive patient activity and ultimately reimbursement, having a seat at the table is crucial.

Some health care systems are run by businesspeople—people with finance backgrounds—and others are led by physicians. In 2017, Becker’s Hospital Review listed the chief executive officers (CEOs) of 183 nonprofit hospital and health systems.¹⁰ Of these, only 25% were led by individuals with an MD. Looking at the 115 largest hospitals in the United States, 30% are physician led.¹⁰ Considering the top 10 hospitals ranked by U.S. News & World Report for 2022, 8 of 10 have a physician at the helm.

Beyond raters and rankers, physician-led hospitals do better. Goodall compared CEOs in the top 100 best hospitals in U.S. News & World Report in 3 key medical specialties: cancer, digestive disorders, and cardiac care.¹¹ The study explored the question: “Are hospitals’ quality ranked more highly when they are led by a medically trained doctor or non-MD professional managers?”¹¹ Analysis revealed that hospital quality scores are about 25% higher in physician-run hospitals than in manager-run hospitals.¹¹ Additional research shows that good management practices correlate with hospital performance, and that “the proportion of managers with a clinical degree has the largest positive effect.”¹²

Several theories exist as to why doctors make good managers in the health care setting.^13,14 Doctors may create a more sympathetic and productive work environment for other clinicians because they are one of them. They have peer-to-peer credibility—because they have walked the walk, they have insight and perspective into how medicine is practiced.

Physicians serve as effective change agents for their organizations in several ways:

• First, physicians take a clinical approach in their leadership roles¹³ and focus on patient care at the center of their decisions. We see the people behind the numbers. Simply put, we humanize the operational side of health care.
• As physicians, we understand the interconnectivity in the practice of medicine. While closing certain service lines may be financially beneficial, these services are often closely linked to profitable service lines.
• Beyond physicians taking a clinical approach to leadership, we emphasize quality.¹³ Because we all have experienced complications and lived through bad outcomes alongside our patients, we understand deeply how important patient safety and quality is, and we are not willing to sacrifice that for financial gain. For us, this is personal. We don’t see our solution to health care challenges as an “or” situation, instead we view it as an “and” situation.
• Physician leaders often can improve medical staff engagement.¹³ A 2018 national survey of physicians found that those who are satisfied with their leadership are more engaged at work, have greater job satisfaction, and are less likely to experience signs of burnout.¹⁵ Physician administrators add value here.

Continue to: Surgeons as leaders...

Surgeons as leaders

What do we know about surgeons as physician leaders? Looking at the previously mentioned lists of physician leaders, surgeons are relatively absent. In the Becker’s Hospital Review study of nonprofit hospitals, only 9% of CEOs were surgeons.¹⁰ In addition, when reviewing data that associated physician leaders and hospital performance, only 3 of the CEOs were surgeons.¹¹ Given that surgeons make up approximately 19% of US physicians, we are underrepresented.

The omission of surgeons as leaders seems inappropriate given that most hospitals are financially reliant on revenue related to surgical care and optimizing this space is an enormous opportunity. Berger and colleagues offered 3 theories as to why there are fewer surgeon leaders¹⁶:

• The relative pay of surgeons exceeds that of most other specialties, and there may be less incentive to accept the challenges presented by leadership roles. (I will add that surgeon leadership is more costly to a system.)
• The craftsmanship nature of surgery discourages the development of other career interests beginning at the trainee level.
• Surgeons have been perceived stereotypically to exhibit arrogance, a characteristic that others may not warm to.

This last observation stings. Successful leadership takes social skill and teamwork.¹⁴ Although medical care is one of the few disciplines in which lack of teamwork might cost lives, physicians are not trained to be team players. We recognize how our training has led us to be lone wolves or gunners, situations where we as individuals had to beat others to secure our spot. We have been trained in command-and-control environments, in stepping up as a leader in highly stressful situations. This part of surgical culture may handicap surgeons in their quest to be health care leaders.

Other traits, however, make us particularly great leaders in health care. Our desire to succeed, willingness to push ourselves to extremes, ability to laser focus on a task, acceptance of delayed gratification, and aptitude for making timely decisions on limited data help us succeed in leadership roles. Seven years of surgical training helped me develop the grit I use every day in the C-suite.

We need more physician and surgeon leadership to thrive in the challenging health care landscape. Berger and colleagues proposed 3 potential solutions to increase the number of surgeons in hospital leadership positions¹⁶:

Nurture future surgical leaders through exposure to management training. Given the contribution to both expense in support services and resources and revenue related to surgical care, each organization needs a content expert to guide these decisions.

Recognize the important contributions that surgeons already make regarding quality, safety, and operational efficiency. An excellent example of this is the American College of Surgeons National Surgical Quality Improvement Program. Because surgeons are content experts in this area, we are primed to lead.

Hospitals, medical schools, and academic departments of surgery should recognize administrative efforts as an important part of the overall academic mission. As the adage states, “No margin, no mission.” We need bright minds to preserve and grow our margins so that we can further invest in our missions.

This is not easy. Given the barriers, this will not happen organically. Charan and colleagues provided an outline for a leadership pathway adapted for physicians (FIGURE).^17,18 It starts with the individual practitioner who is a practicing physician and spends most of their time focused on patient care. As a physician becomes more interested in leadership, they develop new skills and take on more and more responsibility. As they increase in leadership responsibility, they tend to reduce clinical time and increase time spent on strategic and business management. This framework creates a pipeline so that physicians and surgeons can be developed strategically and given increasing responsibility as they develop their capabilities and expand their skill sets.

The leadership challenge

To thrive, we must transform health care by changing how we practice medicine. As ObGyns, we are the leaders we have been waiting for. As you ponder your future, think of your current career and the opportunities you might have. Do you have a seat at the table? What table is that? How are you using your knowledge, expertise, and privilege to advance health care and medicine? I challenge you to critically evaluate this—and lead. ●

ILLUSTRATION: PAUL ZWOLAK

“If you don’t have a seat at the table, you are probably on the menu.” I first heard this quote in 2013, and it launched my interest in health care leadership and influenced me countless times over the last 10 years.

As Chief of Staff at Cleveland Clinic, I oversee nearly 5,000 physicians and scientists across the globe. I am involved in the physician life cycle: recruiting, hiring, privileging and credentialing, talent development, promotion, professionalism, and career transitions. I also sit at the intersection of medical care and the business of medicine. This means leading 18 clinical service lines responsible for 5.6 million visits, 161,000 surgeries, and billions of dollars in operating revenue per year. How I spend most of my time is a far cry from what I spent 11 years’ training to do—gynecologic surgery. This shift in my career was not because I changed my mind about caring for patients or that I tired of being a full-time surgeon. Nothing could be further from the truth. Women’s health remains my “why,” and my leadership journey has taught me that it is critical to have a seat at the table for the sake of ObGyns and women everywhere.

Women’s health on the menu

I will start with a concrete example of when we, as women and ObGyns, were on the menu. In late 2019, the Ohio state House of Representatives introduced a bill that subjected doctors to potential murder charges if they did not try everything to save the life of a mother and fetus, “including attempting to reimplant an ectopic pregnancy into the woman’s uterus.”¹ This bill was based on 2 case reports—one from 1915 and one from 1980—which were both low quality, and the latter case was deemed to be fraudulent.² How did this happen?

An Ohio state representative developed the bill with help from a lobbyist and without input from physicians or content experts. When asked, the representative shared that “he never researched whether re-implanting an ectopic pregnancy into a woman’s uterus was a viable medical procedure before including it in the bill.”³ He added, “I heard about it over the years. I never questioned it or gave it a lot of thought.”³

This example resonates deeply with many of us; it inspires us to speak up and act. As ObGyns, we clearly understand the consequences of legal and regulatory change in women’s health and how it directly impacts our patients and each of us as physicians. Let’s shift to something that you may feel less passion about, but I believe is equally important. This is where obstetrician-gynecologists sit in the intersection of medical care and business. This is the space where I spend most of my time, and from this vantage point, I worry about our field.

The business of medicine

Starting at the macroeconomic level, let’s think about how we as physicians are reimbursed and who makes these decisions. Looking at the national health care expenditure data, Medicare and Medicaid spending makes up nearly 40% of the total spend, and it is growing.⁴ Additionally, private health insurance tends to follow Centers for Medicare and Medicaid Services (CMS) decision making, further compounding its influence.⁴ In simple terms, CMS decides what is covered and how much we are paid. Whether you are in a solo private practice, an employer health care organization, or an academic medical center, physician reimbursement is declining.

In fact, Congress passed its year-end omnibus legislation in the final days of 2022, including a 2% Medicare physician payment cut for 2023,⁵ at a time when expenses to practice medicine, including nonphysician staff and supplies, are at an all-time high and we are living in a 6% inflationary state. This translates into being asked to serve more patients and cut costs. Our day-to-day feels much tighter, and this is why: Medicare physician pay increased just 11% over the past 20 years⁶ (2001–2021) in comparison to the cost of running a medical practice, which increased nearly 40% during that time. In other words, adjusting for inflation in practice costs, Medicare physician payment has fallen 22% over the last 20 years.⁷

Depending on your employment model, you may feel insulated from these changes as increases in reimbursement have occurred in other areas, such as hospitals and ambulatory surgery centers.⁸ In the short term, these increases help, as organizations will see additional funds. But there are 2 main issues: First, it is not nearly enough when you consider the soaring costs of running a hospital. And second, looking at our national population, we rely tremendously on self-employed doctors to serve our patients.

More than 80% of US counties lack adequate health care infrastructure.⁹ More than a third of the US population has less-than-adequate access to pharmacies, primary care physicians, hospitals, trauma centers, and low-cost health centers.⁹ To put things into perspective, more than 20% of counties in the United States are hospital deserts, where most people must drive more than 30 minutes to reach the closest hospital.⁹

There is good reason for this. Operating a hospital is a challenging endeavor. Even before the COVID-19 pandemic and the most recent health care financial challenges, most health care systems and large hospitals operated with very low operating margins (2%–3%). Businesses with similar margins include grocery stores and car dealerships. These low-margin businesses, including health care, rely on high volume for sustainability. High patient volumes distribute expensive hospital costs over many encounters. If physicians cannot sustain practices across the country, it is challenging to have sufficient admission and surgical volumes to justify the cost base of hospitals.

To tie this together, we have very little influence on what we are paid for our services. Reimbursement is declining, which makes it hard to have financially sustainable practices. As hospitals struggle, there is more pressure to prioritize highly profitable service lines, like orthopedics and urology, which are associated with favorable technical revenue. As hospitals are threatened, health care deserts widen, which leaves our entire health care system in jeopardy. Not surprisingly, this most likely affects those who face additional barriers to access, such as those with lower income, limited internet access, and lack of insurance. Together, these barriers further widen disparities in health care outcomes, including outcomes for women. Additionally, this death by a thousand cuts has eroded morale and increased physician burnout.

Transforming how we practice medicine is the only viable solution. I have good news: You are the leaders you have been waiting for.

Continue to: Physicians make good managers...

Physicians make good managers

To successfully transform how we practice medicine, it is critical that those leading the transformation deeply understand how medicine is practiced. The level of understanding required can be achieved only through years of medical practice, as a doctor. We understand how medical teams interact and that different sectors of our health care system are interdependent. Also, because physicians drive patient activity and ultimately reimbursement, having a seat at the table is crucial.

Some health care systems are run by businesspeople—people with finance backgrounds—and others are led by physicians. In 2017, Becker’s Hospital Review listed the chief executive officers (CEOs) of 183 nonprofit hospital and health systems.¹⁰ Of these, only 25% were led by individuals with an MD. Looking at the 115 largest hospitals in the United States, 30% are physician led.¹⁰ Considering the top 10 hospitals ranked by U.S. News & World Report for 2022, 8 of 10 have a physician at the helm.

Beyond raters and rankers, physician-led hospitals do better. Goodall compared CEOs in the top 100 best hospitals in U.S. News & World Report in 3 key medical specialties: cancer, digestive disorders, and cardiac care.¹¹ The study explored the question: “Are hospitals’ quality ranked more highly when they are led by a medically trained doctor or non-MD professional managers?”¹¹ Analysis revealed that hospital quality scores are about 25% higher in physician-run hospitals than in manager-run hospitals.¹¹ Additional research shows that good management practices correlate with hospital performance, and that “the proportion of managers with a clinical degree has the largest positive effect.”¹²

Several theories exist as to why doctors make good managers in the health care setting.^13,14 Doctors may create a more sympathetic and productive work environment for other clinicians because they are one of them. They have peer-to-peer credibility—because they have walked the walk, they have insight and perspective into how medicine is practiced.

Physicians serve as effective change agents for their organizations in several ways:

• First, physicians take a clinical approach in their leadership roles¹³ and focus on patient care at the center of their decisions. We see the people behind the numbers. Simply put, we humanize the operational side of health care.
• As physicians, we understand the interconnectivity in the practice of medicine. While closing certain service lines may be financially beneficial, these services are often closely linked to profitable service lines.
• Beyond physicians taking a clinical approach to leadership, we emphasize quality.¹³ Because we all have experienced complications and lived through bad outcomes alongside our patients, we understand deeply how important patient safety and quality is, and we are not willing to sacrifice that for financial gain. For us, this is personal. We don’t see our solution to health care challenges as an “or” situation, instead we view it as an “and” situation.
• Physician leaders often can improve medical staff engagement.¹³ A 2018 national survey of physicians found that those who are satisfied with their leadership are more engaged at work, have greater job satisfaction, and are less likely to experience signs of burnout.¹⁵ Physician administrators add value here.

Continue to: Surgeons as leaders...

Surgeons as leaders

What do we know about surgeons as physician leaders? Looking at the previously mentioned lists of physician leaders, surgeons are relatively absent. In the Becker’s Hospital Review study of nonprofit hospitals, only 9% of CEOs were surgeons.¹⁰ In addition, when reviewing data that associated physician leaders and hospital performance, only 3 of the CEOs were surgeons.¹¹ Given that surgeons make up approximately 19% of US physicians, we are underrepresented.

The omission of surgeons as leaders seems inappropriate given that most hospitals are financially reliant on revenue related to surgical care and optimizing this space is an enormous opportunity. Berger and colleagues offered 3 theories as to why there are fewer surgeon leaders¹⁶:

• The relative pay of surgeons exceeds that of most other specialties, and there may be less incentive to accept the challenges presented by leadership roles. (I will add that surgeon leadership is more costly to a system.)
• The craftsmanship nature of surgery discourages the development of other career interests beginning at the trainee level.
• Surgeons have been perceived stereotypically to exhibit arrogance, a characteristic that others may not warm to.

This last observation stings. Successful leadership takes social skill and teamwork.¹⁴ Although medical care is one of the few disciplines in which lack of teamwork might cost lives, physicians are not trained to be team players. We recognize how our training has led us to be lone wolves or gunners, situations where we as individuals had to beat others to secure our spot. We have been trained in command-and-control environments, in stepping up as a leader in highly stressful situations. This part of surgical culture may handicap surgeons in their quest to be health care leaders.

Other traits, however, make us particularly great leaders in health care. Our desire to succeed, willingness to push ourselves to extremes, ability to laser focus on a task, acceptance of delayed gratification, and aptitude for making timely decisions on limited data help us succeed in leadership roles. Seven years of surgical training helped me develop the grit I use every day in the C-suite.

We need more physician and surgeon leadership to thrive in the challenging health care landscape. Berger and colleagues proposed 3 potential solutions to increase the number of surgeons in hospital leadership positions¹⁶:

Nurture future surgical leaders through exposure to management training. Given the contribution to both expense in support services and resources and revenue related to surgical care, each organization needs a content expert to guide these decisions.

Recognize the important contributions that surgeons already make regarding quality, safety, and operational efficiency. An excellent example of this is the American College of Surgeons National Surgical Quality Improvement Program. Because surgeons are content experts in this area, we are primed to lead.

Hospitals, medical schools, and academic departments of surgery should recognize administrative efforts as an important part of the overall academic mission. As the adage states, “No margin, no mission.” We need bright minds to preserve and grow our margins so that we can further invest in our missions.

This is not easy. Given the barriers, this will not happen organically. Charan and colleagues provided an outline for a leadership pathway adapted for physicians (FIGURE).^17,18 It starts with the individual practitioner who is a practicing physician and spends most of their time focused on patient care. As a physician becomes more interested in leadership, they develop new skills and take on more and more responsibility. As they increase in leadership responsibility, they tend to reduce clinical time and increase time spent on strategic and business management. This framework creates a pipeline so that physicians and surgeons can be developed strategically and given increasing responsibility as they develop their capabilities and expand their skill sets.

The leadership challenge

To thrive, we must transform health care by changing how we practice medicine. As ObGyns, we are the leaders we have been waiting for. As you ponder your future, think of your current career and the opportunities you might have. Do you have a seat at the table? What table is that? How are you using your knowledge, expertise, and privilege to advance health care and medicine? I challenge you to critically evaluate this—and lead. ●

ILLUSTRATION: PAUL ZWOLAK

“If you don’t have a seat at the table, you are probably on the menu.” I first heard this quote in 2013, and it launched my interest in health care leadership and influenced me countless times over the last 10 years.

As Chief of Staff at Cleveland Clinic, I oversee nearly 5,000 physicians and scientists across the globe. I am involved in the physician life cycle: recruiting, hiring, privileging and credentialing, talent development, promotion, professionalism, and career transitions. I also sit at the intersection of medical care and the business of medicine. This means leading 18 clinical service lines responsible for 5.6 million visits, 161,000 surgeries, and billions of dollars in operating revenue per year. How I spend most of my time is a far cry from what I spent 11 years’ training to do—gynecologic surgery. This shift in my career was not because I changed my mind about caring for patients or that I tired of being a full-time surgeon. Nothing could be further from the truth. Women’s health remains my “why,” and my leadership journey has taught me that it is critical to have a seat at the table for the sake of ObGyns and women everywhere.

Women’s health on the menu

I will start with a concrete example of when we, as women and ObGyns, were on the menu. In late 2019, the Ohio state House of Representatives introduced a bill that subjected doctors to potential murder charges if they did not try everything to save the life of a mother and fetus, “including attempting to reimplant an ectopic pregnancy into the woman’s uterus.”¹ This bill was based on 2 case reports—one from 1915 and one from 1980—which were both low quality, and the latter case was deemed to be fraudulent.² How did this happen?

An Ohio state representative developed the bill with help from a lobbyist and without input from physicians or content experts. When asked, the representative shared that “he never researched whether re-implanting an ectopic pregnancy into a woman’s uterus was a viable medical procedure before including it in the bill.”³ He added, “I heard about it over the years. I never questioned it or gave it a lot of thought.”³

This example resonates deeply with many of us; it inspires us to speak up and act. As ObGyns, we clearly understand the consequences of legal and regulatory change in women’s health and how it directly impacts our patients and each of us as physicians. Let’s shift to something that you may feel less passion about, but I believe is equally important. This is where obstetrician-gynecologists sit in the intersection of medical care and business. This is the space where I spend most of my time, and from this vantage point, I worry about our field.

The business of medicine

Starting at the macroeconomic level, let’s think about how we as physicians are reimbursed and who makes these decisions. Looking at the national health care expenditure data, Medicare and Medicaid spending makes up nearly 40% of the total spend, and it is growing.⁴ Additionally, private health insurance tends to follow Centers for Medicare and Medicaid Services (CMS) decision making, further compounding its influence.⁴ In simple terms, CMS decides what is covered and how much we are paid. Whether you are in a solo private practice, an employer health care organization, or an academic medical center, physician reimbursement is declining.

In fact, Congress passed its year-end omnibus legislation in the final days of 2022, including a 2% Medicare physician payment cut for 2023,⁵ at a time when expenses to practice medicine, including nonphysician staff and supplies, are at an all-time high and we are living in a 6% inflationary state. This translates into being asked to serve more patients and cut costs. Our day-to-day feels much tighter, and this is why: Medicare physician pay increased just 11% over the past 20 years⁶ (2001–2021) in comparison to the cost of running a medical practice, which increased nearly 40% during that time. In other words, adjusting for inflation in practice costs, Medicare physician payment has fallen 22% over the last 20 years.⁷

Depending on your employment model, you may feel insulated from these changes as increases in reimbursement have occurred in other areas, such as hospitals and ambulatory surgery centers.⁸ In the short term, these increases help, as organizations will see additional funds. But there are 2 main issues: First, it is not nearly enough when you consider the soaring costs of running a hospital. And second, looking at our national population, we rely tremendously on self-employed doctors to serve our patients.

More than 80% of US counties lack adequate health care infrastructure.⁹ More than a third of the US population has less-than-adequate access to pharmacies, primary care physicians, hospitals, trauma centers, and low-cost health centers.⁹ To put things into perspective, more than 20% of counties in the United States are hospital deserts, where most people must drive more than 30 minutes to reach the closest hospital.⁹

There is good reason for this. Operating a hospital is a challenging endeavor. Even before the COVID-19 pandemic and the most recent health care financial challenges, most health care systems and large hospitals operated with very low operating margins (2%–3%). Businesses with similar margins include grocery stores and car dealerships. These low-margin businesses, including health care, rely on high volume for sustainability. High patient volumes distribute expensive hospital costs over many encounters. If physicians cannot sustain practices across the country, it is challenging to have sufficient admission and surgical volumes to justify the cost base of hospitals.

To tie this together, we have very little influence on what we are paid for our services. Reimbursement is declining, which makes it hard to have financially sustainable practices. As hospitals struggle, there is more pressure to prioritize highly profitable service lines, like orthopedics and urology, which are associated with favorable technical revenue. As hospitals are threatened, health care deserts widen, which leaves our entire health care system in jeopardy. Not surprisingly, this most likely affects those who face additional barriers to access, such as those with lower income, limited internet access, and lack of insurance. Together, these barriers further widen disparities in health care outcomes, including outcomes for women. Additionally, this death by a thousand cuts has eroded morale and increased physician burnout.

Transforming how we practice medicine is the only viable solution. I have good news: You are the leaders you have been waiting for.

Continue to: Physicians make good managers...

Physicians make good managers

To successfully transform how we practice medicine, it is critical that those leading the transformation deeply understand how medicine is practiced. The level of understanding required can be achieved only through years of medical practice, as a doctor. We understand how medical teams interact and that different sectors of our health care system are interdependent. Also, because physicians drive patient activity and ultimately reimbursement, having a seat at the table is crucial.

Some health care systems are run by businesspeople—people with finance backgrounds—and others are led by physicians. In 2017, Becker’s Hospital Review listed the chief executive officers (CEOs) of 183 nonprofit hospital and health systems.¹⁰ Of these, only 25% were led by individuals with an MD. Looking at the 115 largest hospitals in the United States, 30% are physician led.¹⁰ Considering the top 10 hospitals ranked by U.S. News & World Report for 2022, 8 of 10 have a physician at the helm.

Beyond raters and rankers, physician-led hospitals do better. Goodall compared CEOs in the top 100 best hospitals in U.S. News & World Report in 3 key medical specialties: cancer, digestive disorders, and cardiac care.¹¹ The study explored the question: “Are hospitals’ quality ranked more highly when they are led by a medically trained doctor or non-MD professional managers?”¹¹ Analysis revealed that hospital quality scores are about 25% higher in physician-run hospitals than in manager-run hospitals.¹¹ Additional research shows that good management practices correlate with hospital performance, and that “the proportion of managers with a clinical degree has the largest positive effect.”¹²

Several theories exist as to why doctors make good managers in the health care setting.^13,14 Doctors may create a more sympathetic and productive work environment for other clinicians because they are one of them. They have peer-to-peer credibility—because they have walked the walk, they have insight and perspective into how medicine is practiced.

Physicians serve as effective change agents for their organizations in several ways:

• First, physicians take a clinical approach in their leadership roles¹³ and focus on patient care at the center of their decisions. We see the people behind the numbers. Simply put, we humanize the operational side of health care.
• As physicians, we understand the interconnectivity in the practice of medicine. While closing certain service lines may be financially beneficial, these services are often closely linked to profitable service lines.
• Beyond physicians taking a clinical approach to leadership, we emphasize quality.¹³ Because we all have experienced complications and lived through bad outcomes alongside our patients, we understand deeply how important patient safety and quality is, and we are not willing to sacrifice that for financial gain. For us, this is personal. We don’t see our solution to health care challenges as an “or” situation, instead we view it as an “and” situation.
• Physician leaders often can improve medical staff engagement.¹³ A 2018 national survey of physicians found that those who are satisfied with their leadership are more engaged at work, have greater job satisfaction, and are less likely to experience signs of burnout.¹⁵ Physician administrators add value here.

Continue to: Surgeons as leaders...

Surgeons as leaders

What do we know about surgeons as physician leaders? Looking at the previously mentioned lists of physician leaders, surgeons are relatively absent. In the Becker’s Hospital Review study of nonprofit hospitals, only 9% of CEOs were surgeons.¹⁰ In addition, when reviewing data that associated physician leaders and hospital performance, only 3 of the CEOs were surgeons.¹¹ Given that surgeons make up approximately 19% of US physicians, we are underrepresented.

The omission of surgeons as leaders seems inappropriate given that most hospitals are financially reliant on revenue related to surgical care and optimizing this space is an enormous opportunity. Berger and colleagues offered 3 theories as to why there are fewer surgeon leaders¹⁶:

• The relative pay of surgeons exceeds that of most other specialties, and there may be less incentive to accept the challenges presented by leadership roles. (I will add that surgeon leadership is more costly to a system.)
• The craftsmanship nature of surgery discourages the development of other career interests beginning at the trainee level.
• Surgeons have been perceived stereotypically to exhibit arrogance, a characteristic that others may not warm to.

This last observation stings. Successful leadership takes social skill and teamwork.¹⁴ Although medical care is one of the few disciplines in which lack of teamwork might cost lives, physicians are not trained to be team players. We recognize how our training has led us to be lone wolves or gunners, situations where we as individuals had to beat others to secure our spot. We have been trained in command-and-control environments, in stepping up as a leader in highly stressful situations. This part of surgical culture may handicap surgeons in their quest to be health care leaders.

Other traits, however, make us particularly great leaders in health care. Our desire to succeed, willingness to push ourselves to extremes, ability to laser focus on a task, acceptance of delayed gratification, and aptitude for making timely decisions on limited data help us succeed in leadership roles. Seven years of surgical training helped me develop the grit I use every day in the C-suite.

We need more physician and surgeon leadership to thrive in the challenging health care landscape. Berger and colleagues proposed 3 potential solutions to increase the number of surgeons in hospital leadership positions¹⁶:

Nurture future surgical leaders through exposure to management training. Given the contribution to both expense in support services and resources and revenue related to surgical care, each organization needs a content expert to guide these decisions.

Recognize the important contributions that surgeons already make regarding quality, safety, and operational efficiency. An excellent example of this is the American College of Surgeons National Surgical Quality Improvement Program. Because surgeons are content experts in this area, we are primed to lead.

Hospitals, medical schools, and academic departments of surgery should recognize administrative efforts as an important part of the overall academic mission. As the adage states, “No margin, no mission.” We need bright minds to preserve and grow our margins so that we can further invest in our missions.

This is not easy. Given the barriers, this will not happen organically. Charan and colleagues provided an outline for a leadership pathway adapted for physicians (FIGURE).^17,18 It starts with the individual practitioner who is a practicing physician and spends most of their time focused on patient care. As a physician becomes more interested in leadership, they develop new skills and take on more and more responsibility. As they increase in leadership responsibility, they tend to reduce clinical time and increase time spent on strategic and business management. This framework creates a pipeline so that physicians and surgeons can be developed strategically and given increasing responsibility as they develop their capabilities and expand their skill sets.

The leadership challenge

To thrive, we must transform health care by changing how we practice medicine. As ObGyns, we are the leaders we have been waiting for. As you ponder your future, think of your current career and the opportunities you might have. Do you have a seat at the table? What table is that? How are you using your knowledge, expertise, and privilege to advance health care and medicine? I challenge you to critically evaluate this—and lead. ●