COVID-19 can mean weeks’ long illness, even in young adults and those without chronic conditions who have mild disease and are treated in outpatient settings, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.

Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.

Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.

Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.

Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.

The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.

Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.

Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.

Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.

“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.

Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.

“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.

Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.

“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.

The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
 

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

COVID-19 can mean weeks’ long illness, even in young adults and those without chronic conditions who have mild disease and are treated in outpatient settings, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.

Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.

Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.

Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.

Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.

The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.

Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.

Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.

Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.

“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.

Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.

“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.

Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.

“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.

The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
 

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

COVID-19 can mean weeks’ long illness, even in young adults and those without chronic conditions who have mild disease and are treated in outpatient settings, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.

Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.

Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.

Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.

Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.

The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.

Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.

Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.

Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.

“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.

Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.

“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.

Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.

“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.

The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
 

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

With a long-standing interest in diversity, recent events in the U.S. have intensified the AGA Governing Board’s interest to make a significant impact on the goals enumerated in our diversity policy.

Under the leadership of Dr. Sandra Quezada, AGA Diversity Committee chair, and Dr. Byron Cryer, director of the NIH-funded Fostering Opportunities Resulting in Workforce and Research Diversity (FORWARD Program), the AGA Equity Project task force will develop a multi-year strategic plan to achieve the following aims:

• A just world free of health disparities in digestive diseases and free of inequities in access and effective health care delivery.
• State-of-the-art and well-funded research that aligns with the realities of the current multicultural patient population and disease states to achieve health equity for all.
• A world where it is expected and normal that both members and society leadership structures are diverse, and people of color and women are included in organizational decision making.
• Recognition of accomplishments of diverse leaders. In addition, all leaders recognize, inspire, and cultivate the next generation of prominent, diverse leaders.
• An engaged AGA membership and staff educated about unconscious bias and committed to the eradication of racism and prejudice towards patients, colleagues, and communities.
• The existence of a diverse, culturally and socially aware, large and vocal early-career membership that leads the field toward achieving the vision.

The AGA Governing Board recognizes that meaningful change takes time and have committed to a multi-year effort spanning all aspects of our organization. Although our challenges are formidable, they are not insurmountable.
 

[email protected]

With a long-standing interest in diversity, recent events in the U.S. have intensified the AGA Governing Board’s interest to make a significant impact on the goals enumerated in our diversity policy.

Under the leadership of Dr. Sandra Quezada, AGA Diversity Committee chair, and Dr. Byron Cryer, director of the NIH-funded Fostering Opportunities Resulting in Workforce and Research Diversity (FORWARD Program), the AGA Equity Project task force will develop a multi-year strategic plan to achieve the following aims:

• A just world free of health disparities in digestive diseases and free of inequities in access and effective health care delivery.
• State-of-the-art and well-funded research that aligns with the realities of the current multicultural patient population and disease states to achieve health equity for all.
• A world where it is expected and normal that both members and society leadership structures are diverse, and people of color and women are included in organizational decision making.
• Recognition of accomplishments of diverse leaders. In addition, all leaders recognize, inspire, and cultivate the next generation of prominent, diverse leaders.
• An engaged AGA membership and staff educated about unconscious bias and committed to the eradication of racism and prejudice towards patients, colleagues, and communities.
• The existence of a diverse, culturally and socially aware, large and vocal early-career membership that leads the field toward achieving the vision.

The AGA Governing Board recognizes that meaningful change takes time and have committed to a multi-year effort spanning all aspects of our organization. Although our challenges are formidable, they are not insurmountable.
 

[email protected]

With a long-standing interest in diversity, recent events in the U.S. have intensified the AGA Governing Board’s interest to make a significant impact on the goals enumerated in our diversity policy.

Under the leadership of Dr. Sandra Quezada, AGA Diversity Committee chair, and Dr. Byron Cryer, director of the NIH-funded Fostering Opportunities Resulting in Workforce and Research Diversity (FORWARD Program), the AGA Equity Project task force will develop a multi-year strategic plan to achieve the following aims:

• A just world free of health disparities in digestive diseases and free of inequities in access and effective health care delivery.
• State-of-the-art and well-funded research that aligns with the realities of the current multicultural patient population and disease states to achieve health equity for all.
• A world where it is expected and normal that both members and society leadership structures are diverse, and people of color and women are included in organizational decision making.
• Recognition of accomplishments of diverse leaders. In addition, all leaders recognize, inspire, and cultivate the next generation of prominent, diverse leaders.
• An engaged AGA membership and staff educated about unconscious bias and committed to the eradication of racism and prejudice towards patients, colleagues, and communities.
• The existence of a diverse, culturally and socially aware, large and vocal early-career membership that leads the field toward achieving the vision.

The AGA Governing Board recognizes that meaningful change takes time and have committed to a multi-year effort spanning all aspects of our organization. Although our challenges are formidable, they are not insurmountable.
 

[email protected]

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.

In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:

• Patient case: Elevated aminotransferases of unknown origin. (https://community.gastro.org/posts/21890)

• Patient case: Functional bowel obstruction. (https://community.gastro.org/posts/21888)

• Patient case: Autoimmune hepatitis with chronic hepatitis C. (https://community.gastro.org/posts/21880)

• Patient case: Immunosuppression in IBD (https://community.gastro.org/posts/21860)

• Is COVID-19 reinfection fact or fiction? (https://community.gastro.org/posts/21824)

• Experience with HALO procedures in ambulatory surgery centers. (https://community.gastro.org/posts/21812)

Roundtables (https://community.gastro.org/discussions/)

• GI COVID-19 Connection: Work-life balance in the COVID era.

• Trainee & early career networking connection.

View all upcoming Roundtables in the community at https://community.gastro.org/discussions.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.

In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:

• Patient case: Elevated aminotransferases of unknown origin. (https://community.gastro.org/posts/21890)

• Patient case: Functional bowel obstruction. (https://community.gastro.org/posts/21888)

• Patient case: Autoimmune hepatitis with chronic hepatitis C. (https://community.gastro.org/posts/21880)

• Patient case: Immunosuppression in IBD (https://community.gastro.org/posts/21860)

• Is COVID-19 reinfection fact or fiction? (https://community.gastro.org/posts/21824)

• Experience with HALO procedures in ambulatory surgery centers. (https://community.gastro.org/posts/21812)

Roundtables (https://community.gastro.org/discussions/)

• GI COVID-19 Connection: Work-life balance in the COVID era.

• Trainee & early career networking connection.

View all upcoming Roundtables in the community at https://community.gastro.org/discussions.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.

In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:

• Patient case: Elevated aminotransferases of unknown origin. (https://community.gastro.org/posts/21890)

• Patient case: Functional bowel obstruction. (https://community.gastro.org/posts/21888)

• Patient case: Autoimmune hepatitis with chronic hepatitis C. (https://community.gastro.org/posts/21880)

• Patient case: Immunosuppression in IBD (https://community.gastro.org/posts/21860)

• Is COVID-19 reinfection fact or fiction? (https://community.gastro.org/posts/21824)

• Experience with HALO procedures in ambulatory surgery centers. (https://community.gastro.org/posts/21812)

Roundtables (https://community.gastro.org/discussions/)

• GI COVID-19 Connection: Work-life balance in the COVID era.

• Trainee & early career networking connection.

View all upcoming Roundtables in the community at https://community.gastro.org/discussions.

All infants born to a cohort of 31 COVID-19–positive mothers tested negative for the virus during the height of the New York surge, according to a study out of New York-Presbyterian Hospital.

South_agency/Getty Images

“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.

But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.

“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.

The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.

Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.

The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.

“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.

They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”

The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.

Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”

Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”

Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”

The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”

Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:

• Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
• Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
• There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.

Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”

SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.

All infants born to a cohort of 31 COVID-19–positive mothers tested negative for the virus during the height of the New York surge, according to a study out of New York-Presbyterian Hospital.

South_agency/Getty Images

“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.

But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.

“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.

The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.

Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.

The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.

“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.

They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”

The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.

Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”

Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”

Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”

The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”

Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:

• Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
• Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
• There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.

Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”

SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.

All infants born to a cohort of 31 COVID-19–positive mothers tested negative for the virus during the height of the New York surge, according to a study out of New York-Presbyterian Hospital.

South_agency/Getty Images

“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.

But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.

“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.

The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.

Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.

The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.

“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.

They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”

The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.

Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”

Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”

Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”

The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”

Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:

• Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
• Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
• There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.

Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”

SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.

New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).

decade3d/Thinkstock

In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.

While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).

“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.

“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.

Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
 

Study details

The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.

The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.

The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.

Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.

“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.

Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.

Results in perspective

“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.

“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.

“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.

“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.

In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.

One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.

“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.

But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.

“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.

So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.

“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”

She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”

The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.

SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
 

New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).

decade3d/Thinkstock

In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.

While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).

“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.

“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.

Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
 

Study details

The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.

The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.

The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.

Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.

“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.

Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.

Results in perspective

“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.

“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.

“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.

“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.

In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.

One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.

“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.

But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.

“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.

So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.

“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”

She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”

The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.

SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
 

New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).

decade3d/Thinkstock

In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.

While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).

“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.

“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.

Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
 

Study details

The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.

The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.

The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.

Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.

“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.

Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.

Results in perspective

“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.

“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.

“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.

“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.

In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.

One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.

“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.

But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.

“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.

So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.

“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”

She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”

The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.

SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
 

Since the early 2000s, approximately half of medical students in the United States – and in many years, more than half – have been women, but the proportion of women occupying leadership roles in medicine remains low, according to an update provided at the virtual Pediatric Hospital Medicine.

In pediatrics, a specialty in which approximately 70% of physicians are now women, there has been progress, but still less than 30% of pediatric department chairs are female, said Vincent Chiang, MD, chief medical officer of Boston Children’s Hospital, during a presentation at the virtual meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Citing published data and a survey he personally conducted of the top children’s hospitals identified by the U.S. News and World Report, Dr. Chiang said a minority of division chiefs, chief medical officers, chief financial officers, and other leaders are female. At his institution, only 2 of 16 division chiefs are female.

“No matter how you slice it, women are underrepresented in leadership positions,” he noted.

The problem is certainly not confined to medicine. Dr. Chiang cited data showing that women and men have reached “near parity” in workforce participation in the United States even though the 20% earnings gap has changed little over time.

According to 2020 data from the World Economic Forum, the United States ranked 51 for the gender gap calculated on the basis of economic, political, educational, and health attainment. Even if this places the United States in the top third of the rankings, it is far behind Iceland and the Scandinavian countries that lead the list.

Efforts to reduce structural biases are part of the fix, but Dr. Chiang cautioned that fundamental changes might never occur if the plan is to wait for an approach based on meritocracy. He said that existing structural biases are “slanted away from women,” who are not necessarily granted the opportunities that are readily available to men.

“A meritocracy only works if the initial playing field was level. Otherwise, it just perpetuates the inequalities,” he said.

The problem is not a shortage of women with the skills to lead. In a study by Zenger/Folkman, a consulting company that works on leadership skill development, women performed better than men in 16 of 18 leadership categories, according to Dr. Chiang.

“There is certainly no shortage of capable women,” he noted.

Of the many issues, Dr. Chiang highlighted two. The first is the challenge of placing women on leadership pathways. This is likely to require proactive strategies, such as fast-track advancement programs that guide female candidates toward leadership roles.

The second is more nuanced. According to Dr. Chiang, women who want to assume a leadership role should think more actively about how and who is making decisions at their institution so they can position themselves appropriately. This is nuanced because “there is a certain amount of gamesmanship,” he said. The rise to leadership “has never been a pure meritocracy.”

Importantly, many of the key decisions in any institution involve money, according to Dr. Chiang. As a result, he advised those seeking leadership roles to join audit committees or otherwise take on responsibility for profit-and-loss management. Even in a nonprofit institution, “you need to make the numbers work,” he said, citing the common catchphrase: “No margin, no mission.”

However, Dr. Chiang acknowledged the many obstacles that prevent women from working their way into positions of leadership. For example, networking is important, but women are not necessarily attracted or invited to some of the social engagements, such as golf outings, where strong relationships are created.

In a survey of 100,000 people working at Fortune 500 companies, “82% of women say they feel excluded at work and much of that comes from that informal networking,” Dr. Chiang said. “Whereas 92% of men think they are not excluding women in their daily work.”

There is no single solution, but Dr. Chiang believes that concrete structural changes are needed. Female doctors remain grossly underrepresented in leadership roles even as they now represent more than half of the workforce for many specialties. Based on the need for proactive approaches outlined by Dr. Chiang, it appears unlikely that gender inequality will ever resolve itself.

Lisa S. Rotenstein, MD, who has written on fixing the gender imbalance in health care, including for the Harvard Business Review, said she agreed during an interview that structural changes are critical.

“In order to address current disparities, leaders should be thinking about how to remove both the formal and informal obstacles that prevent women and minorities from getting into the rooms where these decisions are being made,” said Dr. Rotenstein, who is an instructor in medicine at Brigham and Women’s Hospital, Harvard Medical School in Boston.

“This will need to involve sponsorship that gets women invited to the right committees or in positions with responsibility for profit-and-loss management,” she added.

Dr. Rotenstein spoke about improving “access to the pipeline” that leads to leadership roles. The ways in which women are excluded from opportunities is often subtle and difficult to penetrate without fundamental changes, she explained.

“Institutions need to understand the processes that lead to leadership roles and make the changes that allow women and minorities to participate,” she said. It is not enough to recognize the problem, according to Dr. Rotenstein.

Like Dr. Chiang, she noted that changes are needed in the methods that move underrepresented groups into leadership roles.

Dr. Chiang reported no potential conflicts of interest relevant to this study.

Since the early 2000s, approximately half of medical students in the United States – and in many years, more than half – have been women, but the proportion of women occupying leadership roles in medicine remains low, according to an update provided at the virtual Pediatric Hospital Medicine.

In pediatrics, a specialty in which approximately 70% of physicians are now women, there has been progress, but still less than 30% of pediatric department chairs are female, said Vincent Chiang, MD, chief medical officer of Boston Children’s Hospital, during a presentation at the virtual meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Citing published data and a survey he personally conducted of the top children’s hospitals identified by the U.S. News and World Report, Dr. Chiang said a minority of division chiefs, chief medical officers, chief financial officers, and other leaders are female. At his institution, only 2 of 16 division chiefs are female.

“No matter how you slice it, women are underrepresented in leadership positions,” he noted.

The problem is certainly not confined to medicine. Dr. Chiang cited data showing that women and men have reached “near parity” in workforce participation in the United States even though the 20% earnings gap has changed little over time.

According to 2020 data from the World Economic Forum, the United States ranked 51 for the gender gap calculated on the basis of economic, political, educational, and health attainment. Even if this places the United States in the top third of the rankings, it is far behind Iceland and the Scandinavian countries that lead the list.

Efforts to reduce structural biases are part of the fix, but Dr. Chiang cautioned that fundamental changes might never occur if the plan is to wait for an approach based on meritocracy. He said that existing structural biases are “slanted away from women,” who are not necessarily granted the opportunities that are readily available to men.

“A meritocracy only works if the initial playing field was level. Otherwise, it just perpetuates the inequalities,” he said.

The problem is not a shortage of women with the skills to lead. In a study by Zenger/Folkman, a consulting company that works on leadership skill development, women performed better than men in 16 of 18 leadership categories, according to Dr. Chiang.

“There is certainly no shortage of capable women,” he noted.

Of the many issues, Dr. Chiang highlighted two. The first is the challenge of placing women on leadership pathways. This is likely to require proactive strategies, such as fast-track advancement programs that guide female candidates toward leadership roles.

The second is more nuanced. According to Dr. Chiang, women who want to assume a leadership role should think more actively about how and who is making decisions at their institution so they can position themselves appropriately. This is nuanced because “there is a certain amount of gamesmanship,” he said. The rise to leadership “has never been a pure meritocracy.”

Importantly, many of the key decisions in any institution involve money, according to Dr. Chiang. As a result, he advised those seeking leadership roles to join audit committees or otherwise take on responsibility for profit-and-loss management. Even in a nonprofit institution, “you need to make the numbers work,” he said, citing the common catchphrase: “No margin, no mission.”

However, Dr. Chiang acknowledged the many obstacles that prevent women from working their way into positions of leadership. For example, networking is important, but women are not necessarily attracted or invited to some of the social engagements, such as golf outings, where strong relationships are created.

In a survey of 100,000 people working at Fortune 500 companies, “82% of women say they feel excluded at work and much of that comes from that informal networking,” Dr. Chiang said. “Whereas 92% of men think they are not excluding women in their daily work.”

There is no single solution, but Dr. Chiang believes that concrete structural changes are needed. Female doctors remain grossly underrepresented in leadership roles even as they now represent more than half of the workforce for many specialties. Based on the need for proactive approaches outlined by Dr. Chiang, it appears unlikely that gender inequality will ever resolve itself.

Lisa S. Rotenstein, MD, who has written on fixing the gender imbalance in health care, including for the Harvard Business Review, said she agreed during an interview that structural changes are critical.

“In order to address current disparities, leaders should be thinking about how to remove both the formal and informal obstacles that prevent women and minorities from getting into the rooms where these decisions are being made,” said Dr. Rotenstein, who is an instructor in medicine at Brigham and Women’s Hospital, Harvard Medical School in Boston.

“This will need to involve sponsorship that gets women invited to the right committees or in positions with responsibility for profit-and-loss management,” she added.

Dr. Rotenstein spoke about improving “access to the pipeline” that leads to leadership roles. The ways in which women are excluded from opportunities is often subtle and difficult to penetrate without fundamental changes, she explained.

“Institutions need to understand the processes that lead to leadership roles and make the changes that allow women and minorities to participate,” she said. It is not enough to recognize the problem, according to Dr. Rotenstein.

Like Dr. Chiang, she noted that changes are needed in the methods that move underrepresented groups into leadership roles.

Dr. Chiang reported no potential conflicts of interest relevant to this study.

Since the early 2000s, approximately half of medical students in the United States – and in many years, more than half – have been women, but the proportion of women occupying leadership roles in medicine remains low, according to an update provided at the virtual Pediatric Hospital Medicine.

In pediatrics, a specialty in which approximately 70% of physicians are now women, there has been progress, but still less than 30% of pediatric department chairs are female, said Vincent Chiang, MD, chief medical officer of Boston Children’s Hospital, during a presentation at the virtual meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Citing published data and a survey he personally conducted of the top children’s hospitals identified by the U.S. News and World Report, Dr. Chiang said a minority of division chiefs, chief medical officers, chief financial officers, and other leaders are female. At his institution, only 2 of 16 division chiefs are female.

“No matter how you slice it, women are underrepresented in leadership positions,” he noted.

The problem is certainly not confined to medicine. Dr. Chiang cited data showing that women and men have reached “near parity” in workforce participation in the United States even though the 20% earnings gap has changed little over time.

According to 2020 data from the World Economic Forum, the United States ranked 51 for the gender gap calculated on the basis of economic, political, educational, and health attainment. Even if this places the United States in the top third of the rankings, it is far behind Iceland and the Scandinavian countries that lead the list.

Efforts to reduce structural biases are part of the fix, but Dr. Chiang cautioned that fundamental changes might never occur if the plan is to wait for an approach based on meritocracy. He said that existing structural biases are “slanted away from women,” who are not necessarily granted the opportunities that are readily available to men.

“A meritocracy only works if the initial playing field was level. Otherwise, it just perpetuates the inequalities,” he said.

The problem is not a shortage of women with the skills to lead. In a study by Zenger/Folkman, a consulting company that works on leadership skill development, women performed better than men in 16 of 18 leadership categories, according to Dr. Chiang.

“There is certainly no shortage of capable women,” he noted.

Of the many issues, Dr. Chiang highlighted two. The first is the challenge of placing women on leadership pathways. This is likely to require proactive strategies, such as fast-track advancement programs that guide female candidates toward leadership roles.

The second is more nuanced. According to Dr. Chiang, women who want to assume a leadership role should think more actively about how and who is making decisions at their institution so they can position themselves appropriately. This is nuanced because “there is a certain amount of gamesmanship,” he said. The rise to leadership “has never been a pure meritocracy.”

Importantly, many of the key decisions in any institution involve money, according to Dr. Chiang. As a result, he advised those seeking leadership roles to join audit committees or otherwise take on responsibility for profit-and-loss management. Even in a nonprofit institution, “you need to make the numbers work,” he said, citing the common catchphrase: “No margin, no mission.”

However, Dr. Chiang acknowledged the many obstacles that prevent women from working their way into positions of leadership. For example, networking is important, but women are not necessarily attracted or invited to some of the social engagements, such as golf outings, where strong relationships are created.

In a survey of 100,000 people working at Fortune 500 companies, “82% of women say they feel excluded at work and much of that comes from that informal networking,” Dr. Chiang said. “Whereas 92% of men think they are not excluding women in their daily work.”

There is no single solution, but Dr. Chiang believes that concrete structural changes are needed. Female doctors remain grossly underrepresented in leadership roles even as they now represent more than half of the workforce for many specialties. Based on the need for proactive approaches outlined by Dr. Chiang, it appears unlikely that gender inequality will ever resolve itself.

Lisa S. Rotenstein, MD, who has written on fixing the gender imbalance in health care, including for the Harvard Business Review, said she agreed during an interview that structural changes are critical.

“In order to address current disparities, leaders should be thinking about how to remove both the formal and informal obstacles that prevent women and minorities from getting into the rooms where these decisions are being made,” said Dr. Rotenstein, who is an instructor in medicine at Brigham and Women’s Hospital, Harvard Medical School in Boston.

“This will need to involve sponsorship that gets women invited to the right committees or in positions with responsibility for profit-and-loss management,” she added.

Dr. Rotenstein spoke about improving “access to the pipeline” that leads to leadership roles. The ways in which women are excluded from opportunities is often subtle and difficult to penetrate without fundamental changes, she explained.

“Institutions need to understand the processes that lead to leadership roles and make the changes that allow women and minorities to participate,” she said. It is not enough to recognize the problem, according to Dr. Rotenstein.

Like Dr. Chiang, she noted that changes are needed in the methods that move underrepresented groups into leadership roles.

Dr. Chiang reported no potential conflicts of interest relevant to this study.

A 25-year-old woman presents to discuss treatment of her headaches. They occur two or three times a month and last for 4-6 hours. The headaches are disabling, have a pounding quality behind the patient’s right eye, and worsen with exercise. The patient’s neurologic exam is normal.

She has tried oral sumatriptan and naproxen, but neither drug provided her with any relief from the headaches. What treatment would you recommend?
 

A. Topiramate

B. Beta-blocker

C. Lasmiditan

D. Metoclopramide plus sumatriptan

E. Ubrogepant

It is common to see patients with migraine headaches and to see patients with migraines who have not responded to previous migraine therapies. This column will focus on some migraine therapy pearls.

DKart/iStockphoto

For this patient, I would try choice D first, giving metoclopramide with oral sumatriptan to see if it can improve response to sumatriptan. The two new classes of drugs for acute migraine therapy, the gepants and ditans, certainly have a role in patients unresponsive or intolerant of triptans/NSAIDS, but I would try several tricks with these less expensive medications first before entering into prior authorization hell trying to get a gepant or ditan.

When a patient has already used a triptan but experienced no benefit from it, often the next medication a patient tries is a different triptan. Dahlof reviewed four trials that looked at the efficacy of switching sumatriptan nonresponders to a different triptan and found that lack of response to sumatriptan did not predict lack of response to an alternative triptan.¹ Unfortunately, acquiring insurance coverage for an alternate triptan can be difficult.

Other treatment options are nasal or injectable formulations of sumatriptan. Both of these are more costly than oral sumatriptan, and injectable sumatriptan has more side effects than oral triptans.

Combining treatment with metoclopramide can be helpful. In a study by Schulman and Dermott looking at patients who had previously been triptan nonresponders, 63% of those who took metoclopramide with sumatriptan had meaningful pain relief, compared with 31% of those who received sumatriptan and placebo.²

In a different study, Tfelt-Hansen et al. compared treatment with the combination of lysine acetylsalicylate plus metoclopramide versus treatment with 100 mg of sumatriptan.³ There was no difference in outcomes between the two treatment groups, with the lysine acetylsalicylate plus metoclopramide patients having a 57% success rate for first treated migraine compared with 53% of the sumatriptan-treated patients.

Treating with the combination of naproxen plus sumatriptan is superior to treating with either medication alone. Brandes et al. reported on two studies involving the use of the sumatriptan/naproxen combination, compared with using sumatriptan, naproxen, or placebo.⁴ In both, taking the sumatriptan/naproxen combination was superior to taking sumatriptan, naproxen, or placebo (P < .001).

In a study of patients with poor prior response to triptans, Mathew et al. found that the sumatriptan/naproxen combination was superior to placebo for both 2- and 24-hour headache relief (P < .001).⁵
 

Pearl

Try several options before abandoning triptans in previous triptan nonresponders, including trying a different triptan, adding metoclopramide, orcombining with an NSAID.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Dahlöf CG. Infrequent or nonresponse to oral sumatriptan does not predict response to other triptans – review of four trials. Cephalalgia. 2006 Feb;26(2):98-106.

2. Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003 Jul-Aug;43(7):729-33.

3. Tfelt-Hansen P et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995 Oct 7;346(8980):923-6.

4. Brandes JL et al. Sumatriptan‐naproxen for acute treatment of migraine: A randomized trial. JAMA. 2007;297:1443‐54.

5. Mathew NT, Landy S, Stark S, et al. Fixed‐dose sumatriptan and naproxen in poor responders to triptans with a short half‐life. Headache. 2009;49:971‐82.

A 25-year-old woman presents to discuss treatment of her headaches. They occur two or three times a month and last for 4-6 hours. The headaches are disabling, have a pounding quality behind the patient’s right eye, and worsen with exercise. The patient’s neurologic exam is normal.

She has tried oral sumatriptan and naproxen, but neither drug provided her with any relief from the headaches. What treatment would you recommend?
 

A. Topiramate

B. Beta-blocker

C. Lasmiditan

D. Metoclopramide plus sumatriptan

E. Ubrogepant

It is common to see patients with migraine headaches and to see patients with migraines who have not responded to previous migraine therapies. This column will focus on some migraine therapy pearls.

DKart/iStockphoto

For this patient, I would try choice D first, giving metoclopramide with oral sumatriptan to see if it can improve response to sumatriptan. The two new classes of drugs for acute migraine therapy, the gepants and ditans, certainly have a role in patients unresponsive or intolerant of triptans/NSAIDS, but I would try several tricks with these less expensive medications first before entering into prior authorization hell trying to get a gepant or ditan.

When a patient has already used a triptan but experienced no benefit from it, often the next medication a patient tries is a different triptan. Dahlof reviewed four trials that looked at the efficacy of switching sumatriptan nonresponders to a different triptan and found that lack of response to sumatriptan did not predict lack of response to an alternative triptan.¹ Unfortunately, acquiring insurance coverage for an alternate triptan can be difficult.

Other treatment options are nasal or injectable formulations of sumatriptan. Both of these are more costly than oral sumatriptan, and injectable sumatriptan has more side effects than oral triptans.

Combining treatment with metoclopramide can be helpful. In a study by Schulman and Dermott looking at patients who had previously been triptan nonresponders, 63% of those who took metoclopramide with sumatriptan had meaningful pain relief, compared with 31% of those who received sumatriptan and placebo.²

In a different study, Tfelt-Hansen et al. compared treatment with the combination of lysine acetylsalicylate plus metoclopramide versus treatment with 100 mg of sumatriptan.³ There was no difference in outcomes between the two treatment groups, with the lysine acetylsalicylate plus metoclopramide patients having a 57% success rate for first treated migraine compared with 53% of the sumatriptan-treated patients.

Treating with the combination of naproxen plus sumatriptan is superior to treating with either medication alone. Brandes et al. reported on two studies involving the use of the sumatriptan/naproxen combination, compared with using sumatriptan, naproxen, or placebo.⁴ In both, taking the sumatriptan/naproxen combination was superior to taking sumatriptan, naproxen, or placebo (P < .001).

In a study of patients with poor prior response to triptans, Mathew et al. found that the sumatriptan/naproxen combination was superior to placebo for both 2- and 24-hour headache relief (P < .001).⁵
 

Pearl

Try several options before abandoning triptans in previous triptan nonresponders, including trying a different triptan, adding metoclopramide, orcombining with an NSAID.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Dahlöf CG. Infrequent or nonresponse to oral sumatriptan does not predict response to other triptans – review of four trials. Cephalalgia. 2006 Feb;26(2):98-106.

2. Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003 Jul-Aug;43(7):729-33.

3. Tfelt-Hansen P et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995 Oct 7;346(8980):923-6.

4. Brandes JL et al. Sumatriptan‐naproxen for acute treatment of migraine: A randomized trial. JAMA. 2007;297:1443‐54.

5. Mathew NT, Landy S, Stark S, et al. Fixed‐dose sumatriptan and naproxen in poor responders to triptans with a short half‐life. Headache. 2009;49:971‐82.

A 25-year-old woman presents to discuss treatment of her headaches. They occur two or three times a month and last for 4-6 hours. The headaches are disabling, have a pounding quality behind the patient’s right eye, and worsen with exercise. The patient’s neurologic exam is normal.

She has tried oral sumatriptan and naproxen, but neither drug provided her with any relief from the headaches. What treatment would you recommend?
 

A. Topiramate

B. Beta-blocker

C. Lasmiditan

D. Metoclopramide plus sumatriptan

E. Ubrogepant

It is common to see patients with migraine headaches and to see patients with migraines who have not responded to previous migraine therapies. This column will focus on some migraine therapy pearls.

DKart/iStockphoto

For this patient, I would try choice D first, giving metoclopramide with oral sumatriptan to see if it can improve response to sumatriptan. The two new classes of drugs for acute migraine therapy, the gepants and ditans, certainly have a role in patients unresponsive or intolerant of triptans/NSAIDS, but I would try several tricks with these less expensive medications first before entering into prior authorization hell trying to get a gepant or ditan.

When a patient has already used a triptan but experienced no benefit from it, often the next medication a patient tries is a different triptan. Dahlof reviewed four trials that looked at the efficacy of switching sumatriptan nonresponders to a different triptan and found that lack of response to sumatriptan did not predict lack of response to an alternative triptan.¹ Unfortunately, acquiring insurance coverage for an alternate triptan can be difficult.

Other treatment options are nasal or injectable formulations of sumatriptan. Both of these are more costly than oral sumatriptan, and injectable sumatriptan has more side effects than oral triptans.

Combining treatment with metoclopramide can be helpful. In a study by Schulman and Dermott looking at patients who had previously been triptan nonresponders, 63% of those who took metoclopramide with sumatriptan had meaningful pain relief, compared with 31% of those who received sumatriptan and placebo.²

In a different study, Tfelt-Hansen et al. compared treatment with the combination of lysine acetylsalicylate plus metoclopramide versus treatment with 100 mg of sumatriptan.³ There was no difference in outcomes between the two treatment groups, with the lysine acetylsalicylate plus metoclopramide patients having a 57% success rate for first treated migraine compared with 53% of the sumatriptan-treated patients.

Treating with the combination of naproxen plus sumatriptan is superior to treating with either medication alone. Brandes et al. reported on two studies involving the use of the sumatriptan/naproxen combination, compared with using sumatriptan, naproxen, or placebo.⁴ In both, taking the sumatriptan/naproxen combination was superior to taking sumatriptan, naproxen, or placebo (P < .001).

In a study of patients with poor prior response to triptans, Mathew et al. found that the sumatriptan/naproxen combination was superior to placebo for both 2- and 24-hour headache relief (P < .001).⁵
 

Pearl

Try several options before abandoning triptans in previous triptan nonresponders, including trying a different triptan, adding metoclopramide, orcombining with an NSAID.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Dahlöf CG. Infrequent or nonresponse to oral sumatriptan does not predict response to other triptans – review of four trials. Cephalalgia. 2006 Feb;26(2):98-106.

2. Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003 Jul-Aug;43(7):729-33.

3. Tfelt-Hansen P et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995 Oct 7;346(8980):923-6.

4. Brandes JL et al. Sumatriptan‐naproxen for acute treatment of migraine: A randomized trial. JAMA. 2007;297:1443‐54.

5. Mathew NT, Landy S, Stark S, et al. Fixed‐dose sumatriptan and naproxen in poor responders to triptans with a short half‐life. Headache. 2009;49:971‐82.

Ixekizumab appears to be a safe and effective treatment for patients with pityriasis rubra pilaris refractory to other systemic therapies, Teri Greiling, MD, PhD, said at the virtual annual meeting of the American Academy of Dermatology.

The interleukin-17A inhibitor induced long-term remission of pityriasis rubra pilaris (PRP) in 4 of the 11 participants in her open-label, single-arm, 24-week clinical trial of ixekizumab (Taltz) at the Food and Drug Administration–approved dosing for psoriasis. Of 11 patients, 7 experienced at least a 50% reduction in signs and symptoms of the disease. Marked quality-of-life improvements occurred as well, reported Dr. Greiling, a dermatologist at Oregon Health & Science University, Portland.

PRP is a rare papulosquamous disorder that’s challenging to diagnosis and often difficult to treat. Indeed, there is no FDA-approved treatment. The disorder is characterized by widespread follicular keratotic plaques with scale and notable islands of sparing, often with an accompanying waxy yellow palmoplantar keratoderma with fissuring. There are adult- and childhood-onset forms of PRP, as well as sporadic and familial subtypes. Some cases are associated with variants in the CARD14 gene, known to also play a role in familial psoriasis.

Patients with PRP say the disorder has a major adverse impact on their quality of life. Itching and pain are often prominent features.

The 11 study participants, drawn from throughout the United States, were adults with a mean 12-year history of symptoms. All were required to have both clinical and biopsy evidence of PRP. Five had classic adult-onset PRP, five had atypical adult-onset PRP, and one had classic juvenile-onset PRP. All had moderate or severe disease as reflected in a Physician’s Global Assessment score of 3 or 4 on the 0-4 scale. Of the 11, 10 had previously received various systemic therapies for their PRP without success.

Since there is as yet no established PRP severity grading tool, Dr. Greiling applied the principles of the Psoriasis Area and Severity Index (PASI). Participants had a mean baseline PASI score of 24.6, a Dermatology Life Quality Index (DLQI) score of 18, and itch and pain scores of 7 and 6, respectively, on a self-rated 10-point scale.

The primary outcome in the study was change in PASI score at week 24, which was 4 weeks after the final dose of ixekizumab. The mean score improved from 24.8 at week 0 to 9.7 at week 24. Five patients achieved at least a 75% decrease in PASI score, or PASI 75 response, and 2 had a PASI 90 response. The DLQI improved from 18 to 3, and both itch and pain scores dropped to a median of 1. There was no association between response to treatment and PRP clinical subtype.

The four top responders – those with a PASI 89 or better response at week 24 – remained clear or almost clear at week 36, fully 16 weeks after their last dose of ixekizumab. Patients with an intermediate week 24 response – that is, a 50%-85% reduction in PASI score – all relapsed before week 36. The patient with the worst PASI score at both baseline and 24 weeks decided to continue on ixekizumab dosed every 2 weeks independent of the study, rather than at the FDA-approved dosing every 4 weeks for psoriasis, with a resultant drop to a PASI score of 8 at week 36.

To look at mechanism of benefit, Dr. Greiling used quantitative polymerase chain reaction to examine key cytokine expression in the epidermis and dermis. Not surprisingly, IL-17A expression was markedly reduced at both sites, suggesting the importance of the Th17 axis in the pathophysiology of PRP. In contrast, there was no significant change in IL-23 expression.

No serious or unexpected adverse events occurred in the 24-week study.

“In terms of ixekizumab, compared to other treatments, I definitely think it is more effective than any conventional therapies, such as topical steroids, methotrexate, or acitretin,” she said in an interview.

Asked about other biologics, Dr. Greiling said she hasn’t found tumor necrosis factor inhibitors very helpful in her patients with PRP. A formal trial of the IL-17A inhibitor secukinumab (Cosentyx) has been done elsewhere, and although the results haven’t yet been published, her understanding is that the efficacy was similar to her ixekizumab trial.

“I’ve had some of my ixekizumab patients switch to secukinumab, for insurance reasons, though, and had it not be quite as effective, although still helpful,” she said.

Dr. Greiling is now enrolling patients with PRP in a trial of the IL-23 inhibitor guselkumab (Tremfya). It’s her early impression that this may prove to be another therapeutic option.

“I have not yet used brodalumab [Siliq], but I wonder if it would also be helpful, since it seems to have a stronger blockade, working on the IL-17 receptor A,” she said.

She cited two pressing needs that would advance PRP research: the lack of standard criteria for disease diagnosis and the absence of PRP-specific disease measurement tools. “We’re trying to remedy that,” the dermatologist said.

Her study was funded by Eli Lilly. She reported receiving research funding from that company and Janssen.

[email protected]

Ixekizumab appears to be a safe and effective treatment for patients with pityriasis rubra pilaris refractory to other systemic therapies, Teri Greiling, MD, PhD, said at the virtual annual meeting of the American Academy of Dermatology.

The interleukin-17A inhibitor induced long-term remission of pityriasis rubra pilaris (PRP) in 4 of the 11 participants in her open-label, single-arm, 24-week clinical trial of ixekizumab (Taltz) at the Food and Drug Administration–approved dosing for psoriasis. Of 11 patients, 7 experienced at least a 50% reduction in signs and symptoms of the disease. Marked quality-of-life improvements occurred as well, reported Dr. Greiling, a dermatologist at Oregon Health & Science University, Portland.

PRP is a rare papulosquamous disorder that’s challenging to diagnosis and often difficult to treat. Indeed, there is no FDA-approved treatment. The disorder is characterized by widespread follicular keratotic plaques with scale and notable islands of sparing, often with an accompanying waxy yellow palmoplantar keratoderma with fissuring. There are adult- and childhood-onset forms of PRP, as well as sporadic and familial subtypes. Some cases are associated with variants in the CARD14 gene, known to also play a role in familial psoriasis.

Patients with PRP say the disorder has a major adverse impact on their quality of life. Itching and pain are often prominent features.

The 11 study participants, drawn from throughout the United States, were adults with a mean 12-year history of symptoms. All were required to have both clinical and biopsy evidence of PRP. Five had classic adult-onset PRP, five had atypical adult-onset PRP, and one had classic juvenile-onset PRP. All had moderate or severe disease as reflected in a Physician’s Global Assessment score of 3 or 4 on the 0-4 scale. Of the 11, 10 had previously received various systemic therapies for their PRP without success.

Since there is as yet no established PRP severity grading tool, Dr. Greiling applied the principles of the Psoriasis Area and Severity Index (PASI). Participants had a mean baseline PASI score of 24.6, a Dermatology Life Quality Index (DLQI) score of 18, and itch and pain scores of 7 and 6, respectively, on a self-rated 10-point scale.

The primary outcome in the study was change in PASI score at week 24, which was 4 weeks after the final dose of ixekizumab. The mean score improved from 24.8 at week 0 to 9.7 at week 24. Five patients achieved at least a 75% decrease in PASI score, or PASI 75 response, and 2 had a PASI 90 response. The DLQI improved from 18 to 3, and both itch and pain scores dropped to a median of 1. There was no association between response to treatment and PRP clinical subtype.

The four top responders – those with a PASI 89 or better response at week 24 – remained clear or almost clear at week 36, fully 16 weeks after their last dose of ixekizumab. Patients with an intermediate week 24 response – that is, a 50%-85% reduction in PASI score – all relapsed before week 36. The patient with the worst PASI score at both baseline and 24 weeks decided to continue on ixekizumab dosed every 2 weeks independent of the study, rather than at the FDA-approved dosing every 4 weeks for psoriasis, with a resultant drop to a PASI score of 8 at week 36.

To look at mechanism of benefit, Dr. Greiling used quantitative polymerase chain reaction to examine key cytokine expression in the epidermis and dermis. Not surprisingly, IL-17A expression was markedly reduced at both sites, suggesting the importance of the Th17 axis in the pathophysiology of PRP. In contrast, there was no significant change in IL-23 expression.

No serious or unexpected adverse events occurred in the 24-week study.

“In terms of ixekizumab, compared to other treatments, I definitely think it is more effective than any conventional therapies, such as topical steroids, methotrexate, or acitretin,” she said in an interview.

Asked about other biologics, Dr. Greiling said she hasn’t found tumor necrosis factor inhibitors very helpful in her patients with PRP. A formal trial of the IL-17A inhibitor secukinumab (Cosentyx) has been done elsewhere, and although the results haven’t yet been published, her understanding is that the efficacy was similar to her ixekizumab trial.

“I’ve had some of my ixekizumab patients switch to secukinumab, for insurance reasons, though, and had it not be quite as effective, although still helpful,” she said.

Dr. Greiling is now enrolling patients with PRP in a trial of the IL-23 inhibitor guselkumab (Tremfya). It’s her early impression that this may prove to be another therapeutic option.

“I have not yet used brodalumab [Siliq], but I wonder if it would also be helpful, since it seems to have a stronger blockade, working on the IL-17 receptor A,” she said.

She cited two pressing needs that would advance PRP research: the lack of standard criteria for disease diagnosis and the absence of PRP-specific disease measurement tools. “We’re trying to remedy that,” the dermatologist said.

Her study was funded by Eli Lilly. She reported receiving research funding from that company and Janssen.

[email protected]

Ixekizumab appears to be a safe and effective treatment for patients with pityriasis rubra pilaris refractory to other systemic therapies, Teri Greiling, MD, PhD, said at the virtual annual meeting of the American Academy of Dermatology.

The interleukin-17A inhibitor induced long-term remission of pityriasis rubra pilaris (PRP) in 4 of the 11 participants in her open-label, single-arm, 24-week clinical trial of ixekizumab (Taltz) at the Food and Drug Administration–approved dosing for psoriasis. Of 11 patients, 7 experienced at least a 50% reduction in signs and symptoms of the disease. Marked quality-of-life improvements occurred as well, reported Dr. Greiling, a dermatologist at Oregon Health & Science University, Portland.

PRP is a rare papulosquamous disorder that’s challenging to diagnosis and often difficult to treat. Indeed, there is no FDA-approved treatment. The disorder is characterized by widespread follicular keratotic plaques with scale and notable islands of sparing, often with an accompanying waxy yellow palmoplantar keratoderma with fissuring. There are adult- and childhood-onset forms of PRP, as well as sporadic and familial subtypes. Some cases are associated with variants in the CARD14 gene, known to also play a role in familial psoriasis.

Patients with PRP say the disorder has a major adverse impact on their quality of life. Itching and pain are often prominent features.

The 11 study participants, drawn from throughout the United States, were adults with a mean 12-year history of symptoms. All were required to have both clinical and biopsy evidence of PRP. Five had classic adult-onset PRP, five had atypical adult-onset PRP, and one had classic juvenile-onset PRP. All had moderate or severe disease as reflected in a Physician’s Global Assessment score of 3 or 4 on the 0-4 scale. Of the 11, 10 had previously received various systemic therapies for their PRP without success.

Since there is as yet no established PRP severity grading tool, Dr. Greiling applied the principles of the Psoriasis Area and Severity Index (PASI). Participants had a mean baseline PASI score of 24.6, a Dermatology Life Quality Index (DLQI) score of 18, and itch and pain scores of 7 and 6, respectively, on a self-rated 10-point scale.

The primary outcome in the study was change in PASI score at week 24, which was 4 weeks after the final dose of ixekizumab. The mean score improved from 24.8 at week 0 to 9.7 at week 24. Five patients achieved at least a 75% decrease in PASI score, or PASI 75 response, and 2 had a PASI 90 response. The DLQI improved from 18 to 3, and both itch and pain scores dropped to a median of 1. There was no association between response to treatment and PRP clinical subtype.

The four top responders – those with a PASI 89 or better response at week 24 – remained clear or almost clear at week 36, fully 16 weeks after their last dose of ixekizumab. Patients with an intermediate week 24 response – that is, a 50%-85% reduction in PASI score – all relapsed before week 36. The patient with the worst PASI score at both baseline and 24 weeks decided to continue on ixekizumab dosed every 2 weeks independent of the study, rather than at the FDA-approved dosing every 4 weeks for psoriasis, with a resultant drop to a PASI score of 8 at week 36.

To look at mechanism of benefit, Dr. Greiling used quantitative polymerase chain reaction to examine key cytokine expression in the epidermis and dermis. Not surprisingly, IL-17A expression was markedly reduced at both sites, suggesting the importance of the Th17 axis in the pathophysiology of PRP. In contrast, there was no significant change in IL-23 expression.

No serious or unexpected adverse events occurred in the 24-week study.

“In terms of ixekizumab, compared to other treatments, I definitely think it is more effective than any conventional therapies, such as topical steroids, methotrexate, or acitretin,” she said in an interview.

Asked about other biologics, Dr. Greiling said she hasn’t found tumor necrosis factor inhibitors very helpful in her patients with PRP. A formal trial of the IL-17A inhibitor secukinumab (Cosentyx) has been done elsewhere, and although the results haven’t yet been published, her understanding is that the efficacy was similar to her ixekizumab trial.

“I’ve had some of my ixekizumab patients switch to secukinumab, for insurance reasons, though, and had it not be quite as effective, although still helpful,” she said.

Dr. Greiling is now enrolling patients with PRP in a trial of the IL-23 inhibitor guselkumab (Tremfya). It’s her early impression that this may prove to be another therapeutic option.

“I have not yet used brodalumab [Siliq], but I wonder if it would also be helpful, since it seems to have a stronger blockade, working on the IL-17 receptor A,” she said.

She cited two pressing needs that would advance PRP research: the lack of standard criteria for disease diagnosis and the absence of PRP-specific disease measurement tools. “We’re trying to remedy that,” the dermatologist said.

Her study was funded by Eli Lilly. She reported receiving research funding from that company and Janssen.

[email protected]

Reducing the dosing frequency of intravesical bacillus Calmette-Guérin (BCG) was associated with a higher rate of disease recurrence among patients with high-grade non-muscle invasive bladder cancer (NMIBC) in the phase 3 NIMBUS trial.

The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.

More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.

At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.

“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.

“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.

Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.

Trial details

NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.

The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.

Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.

Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.

“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.

Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.

“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
 

Post hoc analysis

Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.

The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).

However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).

Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.

Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.

“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.

“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”

“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.

The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.

SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/

Reducing the dosing frequency of intravesical bacillus Calmette-Guérin (BCG) was associated with a higher rate of disease recurrence among patients with high-grade non-muscle invasive bladder cancer (NMIBC) in the phase 3 NIMBUS trial.

The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.

More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.

At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.

“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.

“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.

Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.

Trial details

NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.

The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.

Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.

Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.

“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.

Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.

“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
 

Post hoc analysis

Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.

The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).

However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).

Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.

Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.

“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.

“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”

“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.

The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.

SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/

Reducing the dosing frequency of intravesical bacillus Calmette-Guérin (BCG) was associated with a higher rate of disease recurrence among patients with high-grade non-muscle invasive bladder cancer (NMIBC) in the phase 3 NIMBUS trial.

The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.

More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.

At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.

“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.

“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.

Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.

Trial details

NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.

The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.

Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.

Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.

“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.

Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.

“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
 

Post hoc analysis

Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.

The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).

However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).

Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.

Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.

“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.

“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”

“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.

The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.

SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/

Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.

Howard Shooter/Thinkstock

Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.

The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.

Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.

The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.

“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.

The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.

Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.

However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.

Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.

Howard Shooter/Thinkstock

Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.

The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.

Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.

The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.

“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.

The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.

Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.

However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.

Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.

Howard Shooter/Thinkstock

Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.

The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.

Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.

The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.

“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.

The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.

Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.

However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.