Clinician Reviews

Racial residential segregation was significantly associated with poor glycemic control in Black adolescents with type 1 diabetes, according to data from 144 individuals.

Racial residential segregation is considered a form of systemic racism that involves limited access to resources, including health care resources, Deborah A. Ellis, MD, of Wayne State University, Detroit, and colleagues wrote in a poster presented at the annual meeting of the American Diabetes Association.

In the study, the researchers recruited youth aged 10-15 years with type 1 diabetes from seven pediatric clinics in two large U.S. cities. The mean age of the participants was 13.3 years, and the mean hemoglobin A1c was 11.5%.

Diabetes management was based on self-reports using the Diabetes Management Scale (DMS). Racial residential segregation, which refers to the separation of groups within a geographic area, was determined using data from the U.S. Census using Location Quotient (LQ) at the block group level; this showed the ratio of the Black population to the total population, compared with the same ratio in the metropolitan area.

The mean family income was $34,163, and the mean LQ was 3.04, “indicating residence in highly segregated neighborhoods,” the researchers wrote.

Overall, racial residential segregation was significantly associated with A1c (P = .001) but not with DMS (P = .311). The researchers also conducted a stepwise multiple regression analysis including age, insulin delivery method, neighborhood adversity (a 9-item composite with variables including percentage of persons living in poverty, percentage of households with no vehicle), and family income. They found that only age, insulin delivery method, and racial residential segregation had significant impacts of A1c levels.

The study was limited by several factors, including the use of self-reports.

However, the results are consistent with previous studies showing the potential negative health effects of structural racism, the researchers wrote. The findings suggest that racial residential segregation has an independent effect on glycemic control in Black youth with type 1 diabetes, and consequently, “advocacy and policy making to address such inequities could improve diabetes population health.”
 

Location makes a difference

“Poor neighborhoods have been associated with high rates of obesity, hypertension, type 2 diabetes and high cholesterol,” Romesh K. Khardori, MD, professor of medicine at Eastern Virginia Medical School, Norfolk, said in an interview. However, “not much is known about impact of racial segregation on type 1 diabetes,” said Dr. Khardori, who was not involved in the study.

Dr. Khardori was not surprised by the current study findings. “In our practice, Black youth coming from racially segregated or low-income housing projects often tend have poor diabetes control, with repeated admissions to local hospitals for managing acute/chronic complications of type 1 diabetes,” he said.

The current findings reflect Dr. Khardori’s clinical experience and highlight the need for clinicians to recognize the increased risk for poor glycemic control and poor outcomes in this vulnerable population.

More research is needed to expand the observations of the current study, Dr. Khardori said. Future researchers also should “involve community leaders and politicians to educate and garner more support for mitigation efforts.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Ellis and Dr. Khardori had no financial conflicts to disclose.

Racial residential segregation was significantly associated with poor glycemic control in Black adolescents with type 1 diabetes, according to data from 144 individuals.

Racial residential segregation is considered a form of systemic racism that involves limited access to resources, including health care resources, Deborah A. Ellis, MD, of Wayne State University, Detroit, and colleagues wrote in a poster presented at the annual meeting of the American Diabetes Association.

In the study, the researchers recruited youth aged 10-15 years with type 1 diabetes from seven pediatric clinics in two large U.S. cities. The mean age of the participants was 13.3 years, and the mean hemoglobin A1c was 11.5%.

Diabetes management was based on self-reports using the Diabetes Management Scale (DMS). Racial residential segregation, which refers to the separation of groups within a geographic area, was determined using data from the U.S. Census using Location Quotient (LQ) at the block group level; this showed the ratio of the Black population to the total population, compared with the same ratio in the metropolitan area.

The mean family income was $34,163, and the mean LQ was 3.04, “indicating residence in highly segregated neighborhoods,” the researchers wrote.

Overall, racial residential segregation was significantly associated with A1c (P = .001) but not with DMS (P = .311). The researchers also conducted a stepwise multiple regression analysis including age, insulin delivery method, neighborhood adversity (a 9-item composite with variables including percentage of persons living in poverty, percentage of households with no vehicle), and family income. They found that only age, insulin delivery method, and racial residential segregation had significant impacts of A1c levels.

The study was limited by several factors, including the use of self-reports.

However, the results are consistent with previous studies showing the potential negative health effects of structural racism, the researchers wrote. The findings suggest that racial residential segregation has an independent effect on glycemic control in Black youth with type 1 diabetes, and consequently, “advocacy and policy making to address such inequities could improve diabetes population health.”
 

Location makes a difference

“Poor neighborhoods have been associated with high rates of obesity, hypertension, type 2 diabetes and high cholesterol,” Romesh K. Khardori, MD, professor of medicine at Eastern Virginia Medical School, Norfolk, said in an interview. However, “not much is known about impact of racial segregation on type 1 diabetes,” said Dr. Khardori, who was not involved in the study.

Dr. Khardori was not surprised by the current study findings. “In our practice, Black youth coming from racially segregated or low-income housing projects often tend have poor diabetes control, with repeated admissions to local hospitals for managing acute/chronic complications of type 1 diabetes,” he said.

The current findings reflect Dr. Khardori’s clinical experience and highlight the need for clinicians to recognize the increased risk for poor glycemic control and poor outcomes in this vulnerable population.

More research is needed to expand the observations of the current study, Dr. Khardori said. Future researchers also should “involve community leaders and politicians to educate and garner more support for mitigation efforts.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Ellis and Dr. Khardori had no financial conflicts to disclose.

Racial residential segregation was significantly associated with poor glycemic control in Black adolescents with type 1 diabetes, according to data from 144 individuals.

Racial residential segregation is considered a form of systemic racism that involves limited access to resources, including health care resources, Deborah A. Ellis, MD, of Wayne State University, Detroit, and colleagues wrote in a poster presented at the annual meeting of the American Diabetes Association.

In the study, the researchers recruited youth aged 10-15 years with type 1 diabetes from seven pediatric clinics in two large U.S. cities. The mean age of the participants was 13.3 years, and the mean hemoglobin A1c was 11.5%.

Diabetes management was based on self-reports using the Diabetes Management Scale (DMS). Racial residential segregation, which refers to the separation of groups within a geographic area, was determined using data from the U.S. Census using Location Quotient (LQ) at the block group level; this showed the ratio of the Black population to the total population, compared with the same ratio in the metropolitan area.

The mean family income was $34,163, and the mean LQ was 3.04, “indicating residence in highly segregated neighborhoods,” the researchers wrote.

Overall, racial residential segregation was significantly associated with A1c (P = .001) but not with DMS (P = .311). The researchers also conducted a stepwise multiple regression analysis including age, insulin delivery method, neighborhood adversity (a 9-item composite with variables including percentage of persons living in poverty, percentage of households with no vehicle), and family income. They found that only age, insulin delivery method, and racial residential segregation had significant impacts of A1c levels.

The study was limited by several factors, including the use of self-reports.

However, the results are consistent with previous studies showing the potential negative health effects of structural racism, the researchers wrote. The findings suggest that racial residential segregation has an independent effect on glycemic control in Black youth with type 1 diabetes, and consequently, “advocacy and policy making to address such inequities could improve diabetes population health.”
 

Location makes a difference

“Poor neighborhoods have been associated with high rates of obesity, hypertension, type 2 diabetes and high cholesterol,” Romesh K. Khardori, MD, professor of medicine at Eastern Virginia Medical School, Norfolk, said in an interview. However, “not much is known about impact of racial segregation on type 1 diabetes,” said Dr. Khardori, who was not involved in the study.

Dr. Khardori was not surprised by the current study findings. “In our practice, Black youth coming from racially segregated or low-income housing projects often tend have poor diabetes control, with repeated admissions to local hospitals for managing acute/chronic complications of type 1 diabetes,” he said.

The current findings reflect Dr. Khardori’s clinical experience and highlight the need for clinicians to recognize the increased risk for poor glycemic control and poor outcomes in this vulnerable population.

More research is needed to expand the observations of the current study, Dr. Khardori said. Future researchers also should “involve community leaders and politicians to educate and garner more support for mitigation efforts.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Ellis and Dr. Khardori had no financial conflicts to disclose.

The Food and Drug Administration has changed the warning about the Volara system to a Class I recall, the most severe level of recall, which is reserved for products that may cause injury or death. At the time of the warning, one injury had been associated with the product; as of June 23, there have been two deaths and one complaint, according to the FDA’s release.

Normally, the Volara system is used for breathing treatments that are administered at home. The medical device company that manufactures it, Baxter International, says the product is designed to help expand the airways and clear mucus for patients who use it. But because of recent product malfunctions, patients are at risk of choking on mucus, developing an infection in their lungs that cuts off their ability to take in oxygen, or in the worst cases, developing brain injury and death.

The risk is especially high because Volara is designed to be used in outpatient settings, not in the hospital under the supervision of a health care professional. It’s supposed to require less supervision than other ventilators. But if there is a problem with the device, or if it’s not connected properly, or if no one is available to assist, people are more likely to be harmed.

People who use the Volara ventilator system at home or people who assist in the use of it should be on alert for these problems. But the FDA advises that patients continue using the therapy if the device has been recommended by a doctor. The device should be used with extra precaution, and patients should be monitored for signs of distress, the release says. Problems while using the device should be reported to the FDA’s Medwatch database.

In addition to these reports, Baxter and its subsidiary company Hillrom say they will update the instructions for the device and will dispatch trainers to make home visits for users. The contact information for the company, as well as additional resources, are listed at the bottom of the release.

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

The Food and Drug Administration has changed the warning about the Volara system to a Class I recall, the most severe level of recall, which is reserved for products that may cause injury or death. At the time of the warning, one injury had been associated with the product; as of June 23, there have been two deaths and one complaint, according to the FDA’s release.

Normally, the Volara system is used for breathing treatments that are administered at home. The medical device company that manufactures it, Baxter International, says the product is designed to help expand the airways and clear mucus for patients who use it. But because of recent product malfunctions, patients are at risk of choking on mucus, developing an infection in their lungs that cuts off their ability to take in oxygen, or in the worst cases, developing brain injury and death.

The risk is especially high because Volara is designed to be used in outpatient settings, not in the hospital under the supervision of a health care professional. It’s supposed to require less supervision than other ventilators. But if there is a problem with the device, or if it’s not connected properly, or if no one is available to assist, people are more likely to be harmed.

People who use the Volara ventilator system at home or people who assist in the use of it should be on alert for these problems. But the FDA advises that patients continue using the therapy if the device has been recommended by a doctor. The device should be used with extra precaution, and patients should be monitored for signs of distress, the release says. Problems while using the device should be reported to the FDA’s Medwatch database.

In addition to these reports, Baxter and its subsidiary company Hillrom say they will update the instructions for the device and will dispatch trainers to make home visits for users. The contact information for the company, as well as additional resources, are listed at the bottom of the release.

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

The Food and Drug Administration has changed the warning about the Volara system to a Class I recall, the most severe level of recall, which is reserved for products that may cause injury or death. At the time of the warning, one injury had been associated with the product; as of June 23, there have been two deaths and one complaint, according to the FDA’s release.

Normally, the Volara system is used for breathing treatments that are administered at home. The medical device company that manufactures it, Baxter International, says the product is designed to help expand the airways and clear mucus for patients who use it. But because of recent product malfunctions, patients are at risk of choking on mucus, developing an infection in their lungs that cuts off their ability to take in oxygen, or in the worst cases, developing brain injury and death.

The risk is especially high because Volara is designed to be used in outpatient settings, not in the hospital under the supervision of a health care professional. It’s supposed to require less supervision than other ventilators. But if there is a problem with the device, or if it’s not connected properly, or if no one is available to assist, people are more likely to be harmed.

People who use the Volara ventilator system at home or people who assist in the use of it should be on alert for these problems. But the FDA advises that patients continue using the therapy if the device has been recommended by a doctor. The device should be used with extra precaution, and patients should be monitored for signs of distress, the release says. Problems while using the device should be reported to the FDA’s Medwatch database.

In addition to these reports, Baxter and its subsidiary company Hillrom say they will update the instructions for the device and will dispatch trainers to make home visits for users. The contact information for the company, as well as additional resources, are listed at the bottom of the release.

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

New data and a new documentary called “The Human Trial” together illuminate the hard work, sacrifice, and slow, iterative progress in the long search for a biological cure for type 1 diabetes.

Opening in select theaters on June 24, the film was written by Los Angeles filmmaker Lisa Hepner, who has type 1 diabetes, and codirected by Ms. Hepner and her husband Guy Mossman, who also filmed it. The couple co-own a film production company.

Abramorama

“The Human Trial” follows the personal journeys of two of the first participants in ViaCyte’s early phase 2 trial of stem cell–derived islet cell transplants, as well as those of the investigators and Ms. Hepner herself, who narrates and appears in the film, interweaving her own experience with type 1 diabetes while acting as a “bridge” between the trial’s participants and scientists. The film spans 7 years of the trial.

The timing of the film’s opening happens to follow presentations at two major medical meetings in early June of more recent islet cell transplantation data from ViaCyte and two other companies, Sernova and Vertex. Each is taking a different practical approach, with the most effective and safe technique yet to be determined.

But all are pursuing the same goal: A biological “cure” for type 1 diabetes with the aim of restoring fully functioning islet cells that can produce insulin and keep blood sugar levels in target range. Ultimately, the hope is to eliminate the need for both exogenous insulin and immunosuppression for all people with type 1 diabetes.

“Cell therapy is an attempt to drastically and substantially change the paradigm of how we actually treat type 1 diabetes,” Manasi S. Jaiman, MD, pediatric endocrinologist and chief medical officer at ViaCyte, said during a presentation at the annual meeting of the Endocrine Society.

Transplantation of cadaver-derived pancreatic islet cells to treat type 1 diabetes dates back more than 20 years to the landmark Edmonton Protocol, with many refinements since. About 1,500 recipients have received them, and roughly a quarter has maintained insulin independence after 10 years, Dr. Jaiman said.

More recently, islets derived from stem cells – either embryonic or autologous – have been used to address the supply and quality problems that arise from cadaveric (dead) donors.

Still, though, the need for lifelong immune suppression means the only current recipients are people with type 1 diabetes for whom the risk of diabetes outweighs that of immune suppression, such as those with hypoglycemic unawareness or extreme glucose swings.

Abramorama

Many research efforts are underway to counter the need for immune suppression by a variety of techniques including cell encapsulation or gene modification.

While the data thus far are encouraging, most of the reports align with what Ms. Hepner says in the film: “We all want stories with a beginning, middle, and end where all the loose pieces fit together. But clinical research is messy and hard. It doesn’t fit into a tidy headline, no matter how much you want it to.”
 

Companies use different approaches for transplanting islets

At ENDO 2022, Dr. Jaiman presented results for three patients who received pancreatic precursor (PEC-01) cells derived from ViaCyte’s proprietary pluripotent stem cell line. The cells are housed in an open delivery device about the size of a standard bandage to allow direct vascularization and are implanted in a patient’s forearm. An earlier version of the device was used in the two patients in “The Human Trial.”

All three patients experienced improved blood glucose levels with lower daily insulin doses and a rise from undetectable C-peptide to levels above 0.3 ng/mL. Of the three, the best results were seen in a 52-year-old woman with type 1 diabetes for 36 years complicated by hypoglycemic unawareness. At 1-year post transplant, her hemoglobin A1c dropped from 7.4% to 6.9%, and time in range [of ideal blood glucose] from 55% to 94%, plus she had a reduction in daily exogenous insulin use of 70%. However, at 18 months her time-in-range had dropped to about 75%.

“We are watching very closely to see what this means,” Dr. Jaiman said.

Further optimization of the approach is planned. “We’re still waiting on the bulk of the data and analyzing it ... We do realize this is a journey but we’re very excited by where we are,” she enthused.

In February 2022, ViaCyte announced it had teamed up with CRISPR Therapeutics to develop an allogeneic, gene-edited stem cell-derived product designed to produce insulin while at the same time evading the immune system.

Preliminary data from another company, Sernova, using a pouch device were presented at the 2022 annual scientific sessions of the American Diabetes Association by Piotr J. Bachul, MD, of the Transplantation Institute at the University of Chicago.

The Sernova Cell Pouch System containing cadaver islets was successfully transplanted into the abdominal wall of six of seven patients. After waiting a month to allow for vascularization, the cells are then placed into the pouch (as opposed to ViaCyte’s method where they are implanted together). The first three patients achieved islet cell graft function – with positive C-peptide – for up to 1 year, although all also required supplemental transplants into the portal vein to achieve insulin independence.

In May 2022, Sernova announced a partnership with Evotec to develop a product that will combine induced pluripotent stem cell (iPSC)-based beta cells for use with the Cell Pouch System.

Clinical testing is scheduled to begin in 2024, a Sernova representative told this news organization.

And as reported earlier in June, findings from Vertex Pharmaceuticals showed success in two patients who received that company›s investigational allogeneic stem-cell derived islets (VX-880), with the first person completely insulin independent 9 months post transplant.

In contrast to the other two companies, Vertex’s approach is to transplant the cells directly to the hepatic portal vein rather than into a subcutaneous pouch.

“The only space that has ever worked efficiently for islets is the liver because they immediately get blood. ... The subcutaneous space is an interesting place, but the problem is it’s not very well vascularized,” James F. Markmann, MD, PhD, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who worked on the Vertex trials, told this news organization.

However, the Sernova representative countered: “With the Cell Pouch transplant, not only can surgeons avoid the risks associated with [hepatic] portal vein infusion – including immediate blood-mediated inflammatory reaction, which is known to kill a large proportion of infused islets – but also liver pathologies.”

Furthermore, the cells remaining in the pouch “may be entirely removed from the patient in the event of a subsequently detected cell quality issue,” which isn’t possible with cells delivered into the portal vein.

“I think it will be interesting how it plays out,” Dr. Markmann said, referring to the field as a whole.

‘The Human Trial’ spotlights the real people behind the data

“The Human Trial” ties together the lives of two young adult study participants: a mother named Maren Badger, who qualified for the study because she regularly experienced severe low blood sugar accompanied by seizures, and Greg Romero, a father who has sight-threatening diabetic retinopathy and other complications, as well as financial hardship.

The film chronicles their experiences over 7 years after receiving the transplant. It’s not easy for either of them to undergo all the implantation and explantation procedures as well as cope with the uncertainty as to whether the transplanted cells are working.

At the same time, the researchers’ emotional and sometimes frustrating journey is shown, as are scenes following company executives to Saudi Arabia and Japan in their pursuit of trial funding.

Ms. Hepner herself is featured pursuing the film’s storyline by frequently questioning company executives, in person and virtually, as well as telling her own story.

A visit to the Banting House Historic Site in London, Ontario, with her young son gives Ms. Hepner the opportunity to explain that after Canadian surgeon Frederick Banting discovered insulin, he sold the patent to the University of Toronto for one dollar.

“One hundred years ago, insulin wasn’t a business. It was a medical breakthrough that saved millions of lives. When Banting accepted his Nobel [Prize], he famously said: ‘Insulin doesn’t belong to me, it belongs to the world.’ ... Now, there’s a $245 billion industry designed to manage our disease,” Ms. Hepner says in the film.

But, she adds: “There’s a catch-22: Biotech needs big pharma’s profits to fund clinical trials. Without that support the researchers wouldn’t have gotten this far. Like most relationships, it’s complicated.”

Nonetheless, the film ultimately uplifts. As one company executive says: “Data show the product is producing insulin in patients for the first time. ... This is a big deal. We know now that the cells work.

“We didn’t know that 5 years ago. All the pieces are there, it’s just a matter of completing the puzzle.”

The ViaCyte work presented by Dr. Jaiman received funding from the European Commission Horizon 2020, the California Institute for Regenerative Medicine, and the JDRF. Jaiman is an employee of ViaCyte. The Sernova work was funded by Sernova and JDRF. Dr. Markmann has reported serving on advisory boards for iTolerance, eGenesis, and Qihan Biotech, and being a consultant for Vertex Pharmaceuticals. Ms. Hepner and Mr. Mossman run LA-based Vox Pop Films, a production company specializing in nonfiction content and commercials. “The Human Trial” was made in collaboration with the nonprofit Beyond Type 1.

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

New data and a new documentary called “The Human Trial” together illuminate the hard work, sacrifice, and slow, iterative progress in the long search for a biological cure for type 1 diabetes.

Opening in select theaters on June 24, the film was written by Los Angeles filmmaker Lisa Hepner, who has type 1 diabetes, and codirected by Ms. Hepner and her husband Guy Mossman, who also filmed it. The couple co-own a film production company.

Abramorama

“The Human Trial” follows the personal journeys of two of the first participants in ViaCyte’s early phase 2 trial of stem cell–derived islet cell transplants, as well as those of the investigators and Ms. Hepner herself, who narrates and appears in the film, interweaving her own experience with type 1 diabetes while acting as a “bridge” between the trial’s participants and scientists. The film spans 7 years of the trial.

The timing of the film’s opening happens to follow presentations at two major medical meetings in early June of more recent islet cell transplantation data from ViaCyte and two other companies, Sernova and Vertex. Each is taking a different practical approach, with the most effective and safe technique yet to be determined.

But all are pursuing the same goal: A biological “cure” for type 1 diabetes with the aim of restoring fully functioning islet cells that can produce insulin and keep blood sugar levels in target range. Ultimately, the hope is to eliminate the need for both exogenous insulin and immunosuppression for all people with type 1 diabetes.

“Cell therapy is an attempt to drastically and substantially change the paradigm of how we actually treat type 1 diabetes,” Manasi S. Jaiman, MD, pediatric endocrinologist and chief medical officer at ViaCyte, said during a presentation at the annual meeting of the Endocrine Society.

Transplantation of cadaver-derived pancreatic islet cells to treat type 1 diabetes dates back more than 20 years to the landmark Edmonton Protocol, with many refinements since. About 1,500 recipients have received them, and roughly a quarter has maintained insulin independence after 10 years, Dr. Jaiman said.

More recently, islets derived from stem cells – either embryonic or autologous – have been used to address the supply and quality problems that arise from cadaveric (dead) donors.

Still, though, the need for lifelong immune suppression means the only current recipients are people with type 1 diabetes for whom the risk of diabetes outweighs that of immune suppression, such as those with hypoglycemic unawareness or extreme glucose swings.

Abramorama

Many research efforts are underway to counter the need for immune suppression by a variety of techniques including cell encapsulation or gene modification.

While the data thus far are encouraging, most of the reports align with what Ms. Hepner says in the film: “We all want stories with a beginning, middle, and end where all the loose pieces fit together. But clinical research is messy and hard. It doesn’t fit into a tidy headline, no matter how much you want it to.”
 

Companies use different approaches for transplanting islets

At ENDO 2022, Dr. Jaiman presented results for three patients who received pancreatic precursor (PEC-01) cells derived from ViaCyte’s proprietary pluripotent stem cell line. The cells are housed in an open delivery device about the size of a standard bandage to allow direct vascularization and are implanted in a patient’s forearm. An earlier version of the device was used in the two patients in “The Human Trial.”

All three patients experienced improved blood glucose levels with lower daily insulin doses and a rise from undetectable C-peptide to levels above 0.3 ng/mL. Of the three, the best results were seen in a 52-year-old woman with type 1 diabetes for 36 years complicated by hypoglycemic unawareness. At 1-year post transplant, her hemoglobin A1c dropped from 7.4% to 6.9%, and time in range [of ideal blood glucose] from 55% to 94%, plus she had a reduction in daily exogenous insulin use of 70%. However, at 18 months her time-in-range had dropped to about 75%.

“We are watching very closely to see what this means,” Dr. Jaiman said.

Further optimization of the approach is planned. “We’re still waiting on the bulk of the data and analyzing it ... We do realize this is a journey but we’re very excited by where we are,” she enthused.

In February 2022, ViaCyte announced it had teamed up with CRISPR Therapeutics to develop an allogeneic, gene-edited stem cell-derived product designed to produce insulin while at the same time evading the immune system.

Preliminary data from another company, Sernova, using a pouch device were presented at the 2022 annual scientific sessions of the American Diabetes Association by Piotr J. Bachul, MD, of the Transplantation Institute at the University of Chicago.

The Sernova Cell Pouch System containing cadaver islets was successfully transplanted into the abdominal wall of six of seven patients. After waiting a month to allow for vascularization, the cells are then placed into the pouch (as opposed to ViaCyte’s method where they are implanted together). The first three patients achieved islet cell graft function – with positive C-peptide – for up to 1 year, although all also required supplemental transplants into the portal vein to achieve insulin independence.

In May 2022, Sernova announced a partnership with Evotec to develop a product that will combine induced pluripotent stem cell (iPSC)-based beta cells for use with the Cell Pouch System.

Clinical testing is scheduled to begin in 2024, a Sernova representative told this news organization.

And as reported earlier in June, findings from Vertex Pharmaceuticals showed success in two patients who received that company›s investigational allogeneic stem-cell derived islets (VX-880), with the first person completely insulin independent 9 months post transplant.

In contrast to the other two companies, Vertex’s approach is to transplant the cells directly to the hepatic portal vein rather than into a subcutaneous pouch.

“The only space that has ever worked efficiently for islets is the liver because they immediately get blood. ... The subcutaneous space is an interesting place, but the problem is it’s not very well vascularized,” James F. Markmann, MD, PhD, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who worked on the Vertex trials, told this news organization.

However, the Sernova representative countered: “With the Cell Pouch transplant, not only can surgeons avoid the risks associated with [hepatic] portal vein infusion – including immediate blood-mediated inflammatory reaction, which is known to kill a large proportion of infused islets – but also liver pathologies.”

Furthermore, the cells remaining in the pouch “may be entirely removed from the patient in the event of a subsequently detected cell quality issue,” which isn’t possible with cells delivered into the portal vein.

“I think it will be interesting how it plays out,” Dr. Markmann said, referring to the field as a whole.

‘The Human Trial’ spotlights the real people behind the data

“The Human Trial” ties together the lives of two young adult study participants: a mother named Maren Badger, who qualified for the study because she regularly experienced severe low blood sugar accompanied by seizures, and Greg Romero, a father who has sight-threatening diabetic retinopathy and other complications, as well as financial hardship.

The film chronicles their experiences over 7 years after receiving the transplant. It’s not easy for either of them to undergo all the implantation and explantation procedures as well as cope with the uncertainty as to whether the transplanted cells are working.

At the same time, the researchers’ emotional and sometimes frustrating journey is shown, as are scenes following company executives to Saudi Arabia and Japan in their pursuit of trial funding.

Ms. Hepner herself is featured pursuing the film’s storyline by frequently questioning company executives, in person and virtually, as well as telling her own story.

A visit to the Banting House Historic Site in London, Ontario, with her young son gives Ms. Hepner the opportunity to explain that after Canadian surgeon Frederick Banting discovered insulin, he sold the patent to the University of Toronto for one dollar.

“One hundred years ago, insulin wasn’t a business. It was a medical breakthrough that saved millions of lives. When Banting accepted his Nobel [Prize], he famously said: ‘Insulin doesn’t belong to me, it belongs to the world.’ ... Now, there’s a $245 billion industry designed to manage our disease,” Ms. Hepner says in the film.

But, she adds: “There’s a catch-22: Biotech needs big pharma’s profits to fund clinical trials. Without that support the researchers wouldn’t have gotten this far. Like most relationships, it’s complicated.”

Nonetheless, the film ultimately uplifts. As one company executive says: “Data show the product is producing insulin in patients for the first time. ... This is a big deal. We know now that the cells work.

“We didn’t know that 5 years ago. All the pieces are there, it’s just a matter of completing the puzzle.”

The ViaCyte work presented by Dr. Jaiman received funding from the European Commission Horizon 2020, the California Institute for Regenerative Medicine, and the JDRF. Jaiman is an employee of ViaCyte. The Sernova work was funded by Sernova and JDRF. Dr. Markmann has reported serving on advisory boards for iTolerance, eGenesis, and Qihan Biotech, and being a consultant for Vertex Pharmaceuticals. Ms. Hepner and Mr. Mossman run LA-based Vox Pop Films, a production company specializing in nonfiction content and commercials. “The Human Trial” was made in collaboration with the nonprofit Beyond Type 1.

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

New data and a new documentary called “The Human Trial” together illuminate the hard work, sacrifice, and slow, iterative progress in the long search for a biological cure for type 1 diabetes.

Opening in select theaters on June 24, the film was written by Los Angeles filmmaker Lisa Hepner, who has type 1 diabetes, and codirected by Ms. Hepner and her husband Guy Mossman, who also filmed it. The couple co-own a film production company.

Abramorama

“The Human Trial” follows the personal journeys of two of the first participants in ViaCyte’s early phase 2 trial of stem cell–derived islet cell transplants, as well as those of the investigators and Ms. Hepner herself, who narrates and appears in the film, interweaving her own experience with type 1 diabetes while acting as a “bridge” between the trial’s participants and scientists. The film spans 7 years of the trial.

The timing of the film’s opening happens to follow presentations at two major medical meetings in early June of more recent islet cell transplantation data from ViaCyte and two other companies, Sernova and Vertex. Each is taking a different practical approach, with the most effective and safe technique yet to be determined.

But all are pursuing the same goal: A biological “cure” for type 1 diabetes with the aim of restoring fully functioning islet cells that can produce insulin and keep blood sugar levels in target range. Ultimately, the hope is to eliminate the need for both exogenous insulin and immunosuppression for all people with type 1 diabetes.

“Cell therapy is an attempt to drastically and substantially change the paradigm of how we actually treat type 1 diabetes,” Manasi S. Jaiman, MD, pediatric endocrinologist and chief medical officer at ViaCyte, said during a presentation at the annual meeting of the Endocrine Society.

Transplantation of cadaver-derived pancreatic islet cells to treat type 1 diabetes dates back more than 20 years to the landmark Edmonton Protocol, with many refinements since. About 1,500 recipients have received them, and roughly a quarter has maintained insulin independence after 10 years, Dr. Jaiman said.

More recently, islets derived from stem cells – either embryonic or autologous – have been used to address the supply and quality problems that arise from cadaveric (dead) donors.

Still, though, the need for lifelong immune suppression means the only current recipients are people with type 1 diabetes for whom the risk of diabetes outweighs that of immune suppression, such as those with hypoglycemic unawareness or extreme glucose swings.

Abramorama

Many research efforts are underway to counter the need for immune suppression by a variety of techniques including cell encapsulation or gene modification.

While the data thus far are encouraging, most of the reports align with what Ms. Hepner says in the film: “We all want stories with a beginning, middle, and end where all the loose pieces fit together. But clinical research is messy and hard. It doesn’t fit into a tidy headline, no matter how much you want it to.”
 

Companies use different approaches for transplanting islets

At ENDO 2022, Dr. Jaiman presented results for three patients who received pancreatic precursor (PEC-01) cells derived from ViaCyte’s proprietary pluripotent stem cell line. The cells are housed in an open delivery device about the size of a standard bandage to allow direct vascularization and are implanted in a patient’s forearm. An earlier version of the device was used in the two patients in “The Human Trial.”

All three patients experienced improved blood glucose levels with lower daily insulin doses and a rise from undetectable C-peptide to levels above 0.3 ng/mL. Of the three, the best results were seen in a 52-year-old woman with type 1 diabetes for 36 years complicated by hypoglycemic unawareness. At 1-year post transplant, her hemoglobin A1c dropped from 7.4% to 6.9%, and time in range [of ideal blood glucose] from 55% to 94%, plus she had a reduction in daily exogenous insulin use of 70%. However, at 18 months her time-in-range had dropped to about 75%.

“We are watching very closely to see what this means,” Dr. Jaiman said.

Further optimization of the approach is planned. “We’re still waiting on the bulk of the data and analyzing it ... We do realize this is a journey but we’re very excited by where we are,” she enthused.

In February 2022, ViaCyte announced it had teamed up with CRISPR Therapeutics to develop an allogeneic, gene-edited stem cell-derived product designed to produce insulin while at the same time evading the immune system.

Preliminary data from another company, Sernova, using a pouch device were presented at the 2022 annual scientific sessions of the American Diabetes Association by Piotr J. Bachul, MD, of the Transplantation Institute at the University of Chicago.

The Sernova Cell Pouch System containing cadaver islets was successfully transplanted into the abdominal wall of six of seven patients. After waiting a month to allow for vascularization, the cells are then placed into the pouch (as opposed to ViaCyte’s method where they are implanted together). The first three patients achieved islet cell graft function – with positive C-peptide – for up to 1 year, although all also required supplemental transplants into the portal vein to achieve insulin independence.

In May 2022, Sernova announced a partnership with Evotec to develop a product that will combine induced pluripotent stem cell (iPSC)-based beta cells for use with the Cell Pouch System.

Clinical testing is scheduled to begin in 2024, a Sernova representative told this news organization.

And as reported earlier in June, findings from Vertex Pharmaceuticals showed success in two patients who received that company›s investigational allogeneic stem-cell derived islets (VX-880), with the first person completely insulin independent 9 months post transplant.

In contrast to the other two companies, Vertex’s approach is to transplant the cells directly to the hepatic portal vein rather than into a subcutaneous pouch.

“The only space that has ever worked efficiently for islets is the liver because they immediately get blood. ... The subcutaneous space is an interesting place, but the problem is it’s not very well vascularized,” James F. Markmann, MD, PhD, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who worked on the Vertex trials, told this news organization.

However, the Sernova representative countered: “With the Cell Pouch transplant, not only can surgeons avoid the risks associated with [hepatic] portal vein infusion – including immediate blood-mediated inflammatory reaction, which is known to kill a large proportion of infused islets – but also liver pathologies.”

Furthermore, the cells remaining in the pouch “may be entirely removed from the patient in the event of a subsequently detected cell quality issue,” which isn’t possible with cells delivered into the portal vein.

“I think it will be interesting how it plays out,” Dr. Markmann said, referring to the field as a whole.

‘The Human Trial’ spotlights the real people behind the data

“The Human Trial” ties together the lives of two young adult study participants: a mother named Maren Badger, who qualified for the study because she regularly experienced severe low blood sugar accompanied by seizures, and Greg Romero, a father who has sight-threatening diabetic retinopathy and other complications, as well as financial hardship.

The film chronicles their experiences over 7 years after receiving the transplant. It’s not easy for either of them to undergo all the implantation and explantation procedures as well as cope with the uncertainty as to whether the transplanted cells are working.

At the same time, the researchers’ emotional and sometimes frustrating journey is shown, as are scenes following company executives to Saudi Arabia and Japan in their pursuit of trial funding.

Ms. Hepner herself is featured pursuing the film’s storyline by frequently questioning company executives, in person and virtually, as well as telling her own story.

A visit to the Banting House Historic Site in London, Ontario, with her young son gives Ms. Hepner the opportunity to explain that after Canadian surgeon Frederick Banting discovered insulin, he sold the patent to the University of Toronto for one dollar.

“One hundred years ago, insulin wasn’t a business. It was a medical breakthrough that saved millions of lives. When Banting accepted his Nobel [Prize], he famously said: ‘Insulin doesn’t belong to me, it belongs to the world.’ ... Now, there’s a $245 billion industry designed to manage our disease,” Ms. Hepner says in the film.

But, she adds: “There’s a catch-22: Biotech needs big pharma’s profits to fund clinical trials. Without that support the researchers wouldn’t have gotten this far. Like most relationships, it’s complicated.”

Nonetheless, the film ultimately uplifts. As one company executive says: “Data show the product is producing insulin in patients for the first time. ... This is a big deal. We know now that the cells work.

“We didn’t know that 5 years ago. All the pieces are there, it’s just a matter of completing the puzzle.”

The ViaCyte work presented by Dr. Jaiman received funding from the European Commission Horizon 2020, the California Institute for Regenerative Medicine, and the JDRF. Jaiman is an employee of ViaCyte. The Sernova work was funded by Sernova and JDRF. Dr. Markmann has reported serving on advisory boards for iTolerance, eGenesis, and Qihan Biotech, and being a consultant for Vertex Pharmaceuticals. Ms. Hepner and Mr. Mossman run LA-based Vox Pop Films, a production company specializing in nonfiction content and commercials. “The Human Trial” was made in collaboration with the nonprofit Beyond Type 1.

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

Women for whom an intrauterine device is inserted from 4 days to 6 weeks after giving birth, as well as those who are breastfeeding, are at higher risk of the contraceptive device puncturing their uterus, new research shows.

The risk of perforation was nearly seven times higher for patients who received an IUD within that window than for those with an IUD who’d never given birth or who were more than a year out from delivery, the researchers found. Health care providers should make patients aware of the heightened risk and should monitor these patients more closely, according to Susan Reed, MD, an ob.gyn. at the University of Washington, Seattle, lead author of the new study.

“I’m a surgeon, and I like to be able to give people good information and good data about risks and benefits for their choices,” Dr. Reed told this news organization. “Uterine perforations related to IUDs are exceedingly rare, and to get good data or known risk factors, you need huge studies. This was the largest study done that really provided accurate information for patients and providers.” The new study, which appears in a recent issue of The Lancet, also found that the risk of uterine perforation was lower if an IUD had been inserted immediately after delivery.

Dr. Reed and colleagues analyzed data from the health records of 326,658 women younger than 50 years for whom an IUD was inserted between 2001 and 2018 at four health care systems. Nearly 30% of these patients received an IUD after giving birth.

The researchers identified a total of 1,008 uterine perforations, for a cumulative incidence at 5 years of 0.6%. The cumulative incidence of uterine perforations was lowest in the group of women who were considered “nonpostpartum”; these women either received an IUD a full year after giving birth or had not given birth during the study period (0.29%; 95% confidence interval, 0.26-0.34).

Women who received an IUD during the 3 days after delivery had a nearly threefold increased risk of an IUD perforation over nonpostpartum women.

In addition, the cumulative incidence of perforation was almost double among breastfeeding women, compared with women who were not breastfeeding. However, Dr. Reed and coauthors noted that breastfeeding is highly beneficial for babies and that the risk of IUD perforation is relatively small.

Among the women who received an IUD following birth, Dr. Reed’s group found that 673 uterine perforations – of which 62% were complete – occurred in breastfeeding individuals, 37% more than for those who did not breastfeed.

Dr. Reed said the study provided some clarity on previous notions that women who’d never given birth were possibly at higher risk for uterine perforation because of smaller uteruses.

“We used to be concerned that women who had never had a pregnancy at all might be at higher risk because their uterus was smaller, the cervix was tighter, and therefore perhaps they might have greater risks,” Dr. Reed said in an interview. “As a clinician and as a provider, it’s pretty exciting to me to be able to tell our younger women who have never had a pregnancy that indeed their risk is lower than anybody else’s.”

The findings help women to make informed decisions, but overall, the benefits of IUDs outweigh the risks, said Monica V. Dragoman, MD, assistant professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai, New York.

“The likelihood of anyone experiencing these types of complications of that population level remains really low,” Dr. Dragoman said.

The findings also provide guidance for providers as to which patients should come in for additional follow-up visits following insertion, Dr. Reed said.

“These are small risks, but it does tell us where we need to consider if there’s a challenging insertion,” Dr. Reed said. “You’re going to look with the ultrasound and make sure the placement looks right. You’re going to give instructions that if the woman has pain or a change in her bleeding pattern, you want to see her back.”

Patients should be aware of the symptoms of uterine perforation – an abrupt change in bleeding pattern and pelvic pain. Perforation correction typically consists of a minimally invasive surgical procedure.

The study was conducted as a result of an order from the Food and Drug Administration to Bayer Pharmaceuticals to evaluate risks of uterine perforation for women who’d received the company’s Mirena IUD. The findings led the company to update the language on the packaging of the device so as to specify the main symptoms of uterine perforations.

The study authors received research funding from Bayer. Multiple authors are employees of Bayer. One study author has in the past received funding from CooperSurgical, Bayer Healthcare Pharmaceutical, and Merck. Bayer was provided the opportunity to review the manuscript before submission, and comments were advisory only.

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

Women for whom an intrauterine device is inserted from 4 days to 6 weeks after giving birth, as well as those who are breastfeeding, are at higher risk of the contraceptive device puncturing their uterus, new research shows.

The risk of perforation was nearly seven times higher for patients who received an IUD within that window than for those with an IUD who’d never given birth or who were more than a year out from delivery, the researchers found. Health care providers should make patients aware of the heightened risk and should monitor these patients more closely, according to Susan Reed, MD, an ob.gyn. at the University of Washington, Seattle, lead author of the new study.

“I’m a surgeon, and I like to be able to give people good information and good data about risks and benefits for their choices,” Dr. Reed told this news organization. “Uterine perforations related to IUDs are exceedingly rare, and to get good data or known risk factors, you need huge studies. This was the largest study done that really provided accurate information for patients and providers.” The new study, which appears in a recent issue of The Lancet, also found that the risk of uterine perforation was lower if an IUD had been inserted immediately after delivery.

Dr. Reed and colleagues analyzed data from the health records of 326,658 women younger than 50 years for whom an IUD was inserted between 2001 and 2018 at four health care systems. Nearly 30% of these patients received an IUD after giving birth.

The researchers identified a total of 1,008 uterine perforations, for a cumulative incidence at 5 years of 0.6%. The cumulative incidence of uterine perforations was lowest in the group of women who were considered “nonpostpartum”; these women either received an IUD a full year after giving birth or had not given birth during the study period (0.29%; 95% confidence interval, 0.26-0.34).

Women who received an IUD during the 3 days after delivery had a nearly threefold increased risk of an IUD perforation over nonpostpartum women.

In addition, the cumulative incidence of perforation was almost double among breastfeeding women, compared with women who were not breastfeeding. However, Dr. Reed and coauthors noted that breastfeeding is highly beneficial for babies and that the risk of IUD perforation is relatively small.

Among the women who received an IUD following birth, Dr. Reed’s group found that 673 uterine perforations – of which 62% were complete – occurred in breastfeeding individuals, 37% more than for those who did not breastfeed.

Dr. Reed said the study provided some clarity on previous notions that women who’d never given birth were possibly at higher risk for uterine perforation because of smaller uteruses.

“We used to be concerned that women who had never had a pregnancy at all might be at higher risk because their uterus was smaller, the cervix was tighter, and therefore perhaps they might have greater risks,” Dr. Reed said in an interview. “As a clinician and as a provider, it’s pretty exciting to me to be able to tell our younger women who have never had a pregnancy that indeed their risk is lower than anybody else’s.”

The findings help women to make informed decisions, but overall, the benefits of IUDs outweigh the risks, said Monica V. Dragoman, MD, assistant professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai, New York.

“The likelihood of anyone experiencing these types of complications of that population level remains really low,” Dr. Dragoman said.

The findings also provide guidance for providers as to which patients should come in for additional follow-up visits following insertion, Dr. Reed said.

“These are small risks, but it does tell us where we need to consider if there’s a challenging insertion,” Dr. Reed said. “You’re going to look with the ultrasound and make sure the placement looks right. You’re going to give instructions that if the woman has pain or a change in her bleeding pattern, you want to see her back.”

Patients should be aware of the symptoms of uterine perforation – an abrupt change in bleeding pattern and pelvic pain. Perforation correction typically consists of a minimally invasive surgical procedure.

The study was conducted as a result of an order from the Food and Drug Administration to Bayer Pharmaceuticals to evaluate risks of uterine perforation for women who’d received the company’s Mirena IUD. The findings led the company to update the language on the packaging of the device so as to specify the main symptoms of uterine perforations.

The study authors received research funding from Bayer. Multiple authors are employees of Bayer. One study author has in the past received funding from CooperSurgical, Bayer Healthcare Pharmaceutical, and Merck. Bayer was provided the opportunity to review the manuscript before submission, and comments were advisory only.

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

Women for whom an intrauterine device is inserted from 4 days to 6 weeks after giving birth, as well as those who are breastfeeding, are at higher risk of the contraceptive device puncturing their uterus, new research shows.

The risk of perforation was nearly seven times higher for patients who received an IUD within that window than for those with an IUD who’d never given birth or who were more than a year out from delivery, the researchers found. Health care providers should make patients aware of the heightened risk and should monitor these patients more closely, according to Susan Reed, MD, an ob.gyn. at the University of Washington, Seattle, lead author of the new study.

“I’m a surgeon, and I like to be able to give people good information and good data about risks and benefits for their choices,” Dr. Reed told this news organization. “Uterine perforations related to IUDs are exceedingly rare, and to get good data or known risk factors, you need huge studies. This was the largest study done that really provided accurate information for patients and providers.” The new study, which appears in a recent issue of The Lancet, also found that the risk of uterine perforation was lower if an IUD had been inserted immediately after delivery.

Dr. Reed and colleagues analyzed data from the health records of 326,658 women younger than 50 years for whom an IUD was inserted between 2001 and 2018 at four health care systems. Nearly 30% of these patients received an IUD after giving birth.

The researchers identified a total of 1,008 uterine perforations, for a cumulative incidence at 5 years of 0.6%. The cumulative incidence of uterine perforations was lowest in the group of women who were considered “nonpostpartum”; these women either received an IUD a full year after giving birth or had not given birth during the study period (0.29%; 95% confidence interval, 0.26-0.34).

Women who received an IUD during the 3 days after delivery had a nearly threefold increased risk of an IUD perforation over nonpostpartum women.

In addition, the cumulative incidence of perforation was almost double among breastfeeding women, compared with women who were not breastfeeding. However, Dr. Reed and coauthors noted that breastfeeding is highly beneficial for babies and that the risk of IUD perforation is relatively small.

Among the women who received an IUD following birth, Dr. Reed’s group found that 673 uterine perforations – of which 62% were complete – occurred in breastfeeding individuals, 37% more than for those who did not breastfeed.

Dr. Reed said the study provided some clarity on previous notions that women who’d never given birth were possibly at higher risk for uterine perforation because of smaller uteruses.

“We used to be concerned that women who had never had a pregnancy at all might be at higher risk because their uterus was smaller, the cervix was tighter, and therefore perhaps they might have greater risks,” Dr. Reed said in an interview. “As a clinician and as a provider, it’s pretty exciting to me to be able to tell our younger women who have never had a pregnancy that indeed their risk is lower than anybody else’s.”

The findings help women to make informed decisions, but overall, the benefits of IUDs outweigh the risks, said Monica V. Dragoman, MD, assistant professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai, New York.

“The likelihood of anyone experiencing these types of complications of that population level remains really low,” Dr. Dragoman said.

The findings also provide guidance for providers as to which patients should come in for additional follow-up visits following insertion, Dr. Reed said.

“These are small risks, but it does tell us where we need to consider if there’s a challenging insertion,” Dr. Reed said. “You’re going to look with the ultrasound and make sure the placement looks right. You’re going to give instructions that if the woman has pain or a change in her bleeding pattern, you want to see her back.”

Patients should be aware of the symptoms of uterine perforation – an abrupt change in bleeding pattern and pelvic pain. Perforation correction typically consists of a minimally invasive surgical procedure.

The study was conducted as a result of an order from the Food and Drug Administration to Bayer Pharmaceuticals to evaluate risks of uterine perforation for women who’d received the company’s Mirena IUD. The findings led the company to update the language on the packaging of the device so as to specify the main symptoms of uterine perforations.

The study authors received research funding from Bayer. Multiple authors are employees of Bayer. One study author has in the past received funding from CooperSurgical, Bayer Healthcare Pharmaceutical, and Merck. Bayer was provided the opportunity to review the manuscript before submission, and comments were advisory only.

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

Endometrial cancer (EC) is the most common gynecologic malignancy and is the fourth most common cancer seen in U.S. women. It is the only major cancer that has continued to see a rise in incidence and mortality for the past 2 decades, and it is anticipated that nearly 66,000 new cases of EC will be diagnosed this year with 12,550 deaths.¹ Given that the well-established risk factors for developing EC including obesity, diabetes, and insulin resistance, the obesity epidemic is indisputably playing a significant role in the increasing incidence.

Historically, White women were thought to have the highest incidence of EC; however, this incidence rate did not account for hysterectomy prevalence, which can vary widely by numerous factors including age, race, ethnicity, and geographic region. When correcting EC incidence rates for prevalence of hysterectomy, Black women have had the highest incidence of EC since 2007, and rates continue to climb.² In fact, the average annual percent change (APC) in EC incidence from 2000 to 2015 was stable for White women at 0.2% while Black women had a near order of magnitude greater APC at 2.1%.²

Differing incidence rates of EC can also be seen by histologic subtype. Endometrioid EC is the more common and less lethal histology of EC that often coincides with the type I classification of EC. These tumors are estrogen driven; therefore, they are associated with conditions resulting in excess estrogen (for example, anovulation, obesity, and hyperlipidemia). Nonendometrioid histologies, primarily composed of serous tumors, are more rare, are typically more aggressive, are not estrogen driven, and are commonly classified as type II tumors. Racial differences between type I and type II tumors are seen with White women more commonly being diagnosed with type I tumors while Black women more typically have type II tumors. White women have the greatest incidence rate of endometrioid EC with an APC that remained relatively unchanged from 2000 to 2015. Black women’s APC in incidence rate of endometrioid EC has increased during this same period at 1.3%. For nonendometrioid tumors, an increasing incidence is seen in all races and ethnicities; however, Black women have a much higher incidence of these tumors, with a rate that continues to increase at an APC of 3.2%.²

EC incidence is increasing with a particularly concerning rise in those who report Black race, but are these same disparities being seen in EC mortality? Unfortunately, drastic disparities are seen in survival data for Black women afflicted with EC. Black patients are more likely to be diagnosed with advanced or metastatic EC and less likely to be diagnosed with localized tumors. While being diagnosed with a more advanced stage of disease does affect survival in EC, Black patients have worse survival regardless of stage of disease at the time of diagnosis.¹ As discussed earlier, the more aggressive type II tumors are composed of nonendometrioid histologies and are more common in Black women. This could lead to the false assumption that these higher-risk tumors are why Black women are disproportionately dying from EC; however, when examining survival by histologic subtype, Black women are more frequently dying from the lower-risk endometrioid EC regardless of stage of disease. The same disparate survival outcomes are also seen in nonendometrioid histologies.² Thus, Black patients have the lowest survival rates irrespective of stage at diagnosis or histologic subtype.

The disparities seen in EC mortality are not new. They can be seen in data for over 30 years and are only widening. While there has been an increase in mortality rates from EC across all races and ethnicities from 2015 to 2019 compared with 1990 to 1994, the mortality rate ratio for Black women compared with White women has increased from 1.83 in 1990-1994 to 1.98 in 2015-2019.³ In the early 1990s, the risk of death from ovarian cancer was twice that of EC. The mortality of EC is now similar to that of ovarian cancer. This threshold in mortality ratio of EC to ovarian cancer has already been seen in Black women, who have experienced greater mortality in EC compared with ovarian cancer since 2005. In fact, the EC mortality of Black women in 2019 was similar to the mortality of White women with ovarian cancer nearly 30 years ago.³

Decades of data have demonstrated the glaring racial disparities seen in EC, and yet, no significant progress has been made in addressing this inequity. Oncology research is now beginning to move beyond describing these differences to a strategy of achieving equitable cancer care. While the study frameworks and novel investigations aimed at addressing the disparities in EC is outside the scope of this article, disparities in clinical trial enrollment continue to exist.

A recent example can be seen in the practice-changing KEYNOTE-775 trial, which led to the Food and Drug Administration approval of lenvatinib plus pembrolizumab in EC treatment.⁴ A total of 827 patients with EC that progressed or recurred following treatment with platinum-based chemotherapy were enrolled in this multinational, multicenter trial. Thirty-one (3.7%) of the patients enrolled were Black. Of those who were enrolled in the United States, 14% were Black. The authors report that this proportion of Black patients in the United States is consistent with 2020 census data, which reported 13.4% of people identified as Black. However, using census data as a benchmark for equitable enrollment is inappropriate. Certain demographic groups are historically more difficult to count, and the COVID-19 pandemic exacerbated the challenge in obtaining an accurate count through job loss, government distrust, and access restrictions resulting in an estimated net undercount of 2.45% in those who report Black race.⁵ Composition of trial enrollment should mirror the population that will be affected by the study results. As advanced EC disproportionately affects Black patients, their enrollment must be higher in these pivotal trials. How else are we to know if these novel therapeutics will work in the population that is most afflicted by EC?

Future studies must account for socioeconomic factors while acknowledging the role of social determinants of health. It is imperative that we use the knowledge that race is a social construct created to control access to power and that there are biologic responses to environmental stresses, including that of racism, affecting health and disease. Changes at every level, from individual practitioners up to federal policies, will need to be enacted or else the unacceptable status quo will continue.
 

Dr. Burkett is a clinical fellow in the division of gynecologic oncology, department of obstetrics and gynecology, at the University of North Carolina at Chapel Hill.

References

1. Siegel RL et al. CA Cancer J Clin. 2022;72:7-33.

2. Clarke MA et al. J Clin Oncol. 2019;37:1895-908.

3. Giaquinto AN et al. Obstet Gynecol. 2022;139:440-2.

4. Makker V et al. N Engl J Med. 2022;386:437-48.

5. Elliott D et al. Simulating the 2020 Census: Miscounts and the fairness of outcomes. Urban Institute; 2021.

Endometrial cancer (EC) is the most common gynecologic malignancy and is the fourth most common cancer seen in U.S. women. It is the only major cancer that has continued to see a rise in incidence and mortality for the past 2 decades, and it is anticipated that nearly 66,000 new cases of EC will be diagnosed this year with 12,550 deaths.¹ Given that the well-established risk factors for developing EC including obesity, diabetes, and insulin resistance, the obesity epidemic is indisputably playing a significant role in the increasing incidence.

Historically, White women were thought to have the highest incidence of EC; however, this incidence rate did not account for hysterectomy prevalence, which can vary widely by numerous factors including age, race, ethnicity, and geographic region. When correcting EC incidence rates for prevalence of hysterectomy, Black women have had the highest incidence of EC since 2007, and rates continue to climb.² In fact, the average annual percent change (APC) in EC incidence from 2000 to 2015 was stable for White women at 0.2% while Black women had a near order of magnitude greater APC at 2.1%.²

Differing incidence rates of EC can also be seen by histologic subtype. Endometrioid EC is the more common and less lethal histology of EC that often coincides with the type I classification of EC. These tumors are estrogen driven; therefore, they are associated with conditions resulting in excess estrogen (for example, anovulation, obesity, and hyperlipidemia). Nonendometrioid histologies, primarily composed of serous tumors, are more rare, are typically more aggressive, are not estrogen driven, and are commonly classified as type II tumors. Racial differences between type I and type II tumors are seen with White women more commonly being diagnosed with type I tumors while Black women more typically have type II tumors. White women have the greatest incidence rate of endometrioid EC with an APC that remained relatively unchanged from 2000 to 2015. Black women’s APC in incidence rate of endometrioid EC has increased during this same period at 1.3%. For nonendometrioid tumors, an increasing incidence is seen in all races and ethnicities; however, Black women have a much higher incidence of these tumors, with a rate that continues to increase at an APC of 3.2%.²

EC incidence is increasing with a particularly concerning rise in those who report Black race, but are these same disparities being seen in EC mortality? Unfortunately, drastic disparities are seen in survival data for Black women afflicted with EC. Black patients are more likely to be diagnosed with advanced or metastatic EC and less likely to be diagnosed with localized tumors. While being diagnosed with a more advanced stage of disease does affect survival in EC, Black patients have worse survival regardless of stage of disease at the time of diagnosis.¹ As discussed earlier, the more aggressive type II tumors are composed of nonendometrioid histologies and are more common in Black women. This could lead to the false assumption that these higher-risk tumors are why Black women are disproportionately dying from EC; however, when examining survival by histologic subtype, Black women are more frequently dying from the lower-risk endometrioid EC regardless of stage of disease. The same disparate survival outcomes are also seen in nonendometrioid histologies.² Thus, Black patients have the lowest survival rates irrespective of stage at diagnosis or histologic subtype.

The disparities seen in EC mortality are not new. They can be seen in data for over 30 years and are only widening. While there has been an increase in mortality rates from EC across all races and ethnicities from 2015 to 2019 compared with 1990 to 1994, the mortality rate ratio for Black women compared with White women has increased from 1.83 in 1990-1994 to 1.98 in 2015-2019.³ In the early 1990s, the risk of death from ovarian cancer was twice that of EC. The mortality of EC is now similar to that of ovarian cancer. This threshold in mortality ratio of EC to ovarian cancer has already been seen in Black women, who have experienced greater mortality in EC compared with ovarian cancer since 2005. In fact, the EC mortality of Black women in 2019 was similar to the mortality of White women with ovarian cancer nearly 30 years ago.³

Decades of data have demonstrated the glaring racial disparities seen in EC, and yet, no significant progress has been made in addressing this inequity. Oncology research is now beginning to move beyond describing these differences to a strategy of achieving equitable cancer care. While the study frameworks and novel investigations aimed at addressing the disparities in EC is outside the scope of this article, disparities in clinical trial enrollment continue to exist.

A recent example can be seen in the practice-changing KEYNOTE-775 trial, which led to the Food and Drug Administration approval of lenvatinib plus pembrolizumab in EC treatment.⁴ A total of 827 patients with EC that progressed or recurred following treatment with platinum-based chemotherapy were enrolled in this multinational, multicenter trial. Thirty-one (3.7%) of the patients enrolled were Black. Of those who were enrolled in the United States, 14% were Black. The authors report that this proportion of Black patients in the United States is consistent with 2020 census data, which reported 13.4% of people identified as Black. However, using census data as a benchmark for equitable enrollment is inappropriate. Certain demographic groups are historically more difficult to count, and the COVID-19 pandemic exacerbated the challenge in obtaining an accurate count through job loss, government distrust, and access restrictions resulting in an estimated net undercount of 2.45% in those who report Black race.⁵ Composition of trial enrollment should mirror the population that will be affected by the study results. As advanced EC disproportionately affects Black patients, their enrollment must be higher in these pivotal trials. How else are we to know if these novel therapeutics will work in the population that is most afflicted by EC?

Future studies must account for socioeconomic factors while acknowledging the role of social determinants of health. It is imperative that we use the knowledge that race is a social construct created to control access to power and that there are biologic responses to environmental stresses, including that of racism, affecting health and disease. Changes at every level, from individual practitioners up to federal policies, will need to be enacted or else the unacceptable status quo will continue.
 

Dr. Burkett is a clinical fellow in the division of gynecologic oncology, department of obstetrics and gynecology, at the University of North Carolina at Chapel Hill.

References

1. Siegel RL et al. CA Cancer J Clin. 2022;72:7-33.

2. Clarke MA et al. J Clin Oncol. 2019;37:1895-908.

3. Giaquinto AN et al. Obstet Gynecol. 2022;139:440-2.

4. Makker V et al. N Engl J Med. 2022;386:437-48.

5. Elliott D et al. Simulating the 2020 Census: Miscounts and the fairness of outcomes. Urban Institute; 2021.

Endometrial cancer (EC) is the most common gynecologic malignancy and is the fourth most common cancer seen in U.S. women. It is the only major cancer that has continued to see a rise in incidence and mortality for the past 2 decades, and it is anticipated that nearly 66,000 new cases of EC will be diagnosed this year with 12,550 deaths.¹ Given that the well-established risk factors for developing EC including obesity, diabetes, and insulin resistance, the obesity epidemic is indisputably playing a significant role in the increasing incidence.

Historically, White women were thought to have the highest incidence of EC; however, this incidence rate did not account for hysterectomy prevalence, which can vary widely by numerous factors including age, race, ethnicity, and geographic region. When correcting EC incidence rates for prevalence of hysterectomy, Black women have had the highest incidence of EC since 2007, and rates continue to climb.² In fact, the average annual percent change (APC) in EC incidence from 2000 to 2015 was stable for White women at 0.2% while Black women had a near order of magnitude greater APC at 2.1%.²

Differing incidence rates of EC can also be seen by histologic subtype. Endometrioid EC is the more common and less lethal histology of EC that often coincides with the type I classification of EC. These tumors are estrogen driven; therefore, they are associated with conditions resulting in excess estrogen (for example, anovulation, obesity, and hyperlipidemia). Nonendometrioid histologies, primarily composed of serous tumors, are more rare, are typically more aggressive, are not estrogen driven, and are commonly classified as type II tumors. Racial differences between type I and type II tumors are seen with White women more commonly being diagnosed with type I tumors while Black women more typically have type II tumors. White women have the greatest incidence rate of endometrioid EC with an APC that remained relatively unchanged from 2000 to 2015. Black women’s APC in incidence rate of endometrioid EC has increased during this same period at 1.3%. For nonendometrioid tumors, an increasing incidence is seen in all races and ethnicities; however, Black women have a much higher incidence of these tumors, with a rate that continues to increase at an APC of 3.2%.²

EC incidence is increasing with a particularly concerning rise in those who report Black race, but are these same disparities being seen in EC mortality? Unfortunately, drastic disparities are seen in survival data for Black women afflicted with EC. Black patients are more likely to be diagnosed with advanced or metastatic EC and less likely to be diagnosed with localized tumors. While being diagnosed with a more advanced stage of disease does affect survival in EC, Black patients have worse survival regardless of stage of disease at the time of diagnosis.¹ As discussed earlier, the more aggressive type II tumors are composed of nonendometrioid histologies and are more common in Black women. This could lead to the false assumption that these higher-risk tumors are why Black women are disproportionately dying from EC; however, when examining survival by histologic subtype, Black women are more frequently dying from the lower-risk endometrioid EC regardless of stage of disease. The same disparate survival outcomes are also seen in nonendometrioid histologies.² Thus, Black patients have the lowest survival rates irrespective of stage at diagnosis or histologic subtype.

The disparities seen in EC mortality are not new. They can be seen in data for over 30 years and are only widening. While there has been an increase in mortality rates from EC across all races and ethnicities from 2015 to 2019 compared with 1990 to 1994, the mortality rate ratio for Black women compared with White women has increased from 1.83 in 1990-1994 to 1.98 in 2015-2019.³ In the early 1990s, the risk of death from ovarian cancer was twice that of EC. The mortality of EC is now similar to that of ovarian cancer. This threshold in mortality ratio of EC to ovarian cancer has already been seen in Black women, who have experienced greater mortality in EC compared with ovarian cancer since 2005. In fact, the EC mortality of Black women in 2019 was similar to the mortality of White women with ovarian cancer nearly 30 years ago.³

Decades of data have demonstrated the glaring racial disparities seen in EC, and yet, no significant progress has been made in addressing this inequity. Oncology research is now beginning to move beyond describing these differences to a strategy of achieving equitable cancer care. While the study frameworks and novel investigations aimed at addressing the disparities in EC is outside the scope of this article, disparities in clinical trial enrollment continue to exist.

A recent example can be seen in the practice-changing KEYNOTE-775 trial, which led to the Food and Drug Administration approval of lenvatinib plus pembrolizumab in EC treatment.⁴ A total of 827 patients with EC that progressed or recurred following treatment with platinum-based chemotherapy were enrolled in this multinational, multicenter trial. Thirty-one (3.7%) of the patients enrolled were Black. Of those who were enrolled in the United States, 14% were Black. The authors report that this proportion of Black patients in the United States is consistent with 2020 census data, which reported 13.4% of people identified as Black. However, using census data as a benchmark for equitable enrollment is inappropriate. Certain demographic groups are historically more difficult to count, and the COVID-19 pandemic exacerbated the challenge in obtaining an accurate count through job loss, government distrust, and access restrictions resulting in an estimated net undercount of 2.45% in those who report Black race.⁵ Composition of trial enrollment should mirror the population that will be affected by the study results. As advanced EC disproportionately affects Black patients, their enrollment must be higher in these pivotal trials. How else are we to know if these novel therapeutics will work in the population that is most afflicted by EC?

Future studies must account for socioeconomic factors while acknowledging the role of social determinants of health. It is imperative that we use the knowledge that race is a social construct created to control access to power and that there are biologic responses to environmental stresses, including that of racism, affecting health and disease. Changes at every level, from individual practitioners up to federal policies, will need to be enacted or else the unacceptable status quo will continue.
 

Dr. Burkett is a clinical fellow in the division of gynecologic oncology, department of obstetrics and gynecology, at the University of North Carolina at Chapel Hill.

References

1. Siegel RL et al. CA Cancer J Clin. 2022;72:7-33.

2. Clarke MA et al. J Clin Oncol. 2019;37:1895-908.

3. Giaquinto AN et al. Obstet Gynecol. 2022;139:440-2.

4. Makker V et al. N Engl J Med. 2022;386:437-48.

5. Elliott D et al. Simulating the 2020 Census: Miscounts and the fairness of outcomes. Urban Institute; 2021.

The Food and Drug Administration has ordered Juul Labs to stop selling e-cigarettes and vaping products on the U.S. market, the agency announced June 23.

The marketing denial order covers all the company’s products in the United States, which means Juul must stop distributing the products and remove everything on the market. That includes the Juul device and flavor replacement pods in the tobacco and menthol flavors.

“Today’s action is further progress on the FDA’s commitment to ensuring that all e-cigarette and electronic nicotine delivery system products currently being marketed to consumers meet our public health standards,” Robert Califf, MD, the FDA commissioner, said in the announcement.

“The agency has dedicated significant resources to review products from the companies that account for most of the U.S. market,” he said. “We recognize these make up a significant part of the available products and many have played a disproportionate role in the rise in youth vaping.”

The marketing denial order covers only the commercial distribution and retail sale of Juul’s products and doesn’t restrict consumer possession or use. The FDA “cannot and will not” enforce actions against consumers, the agency said.

The order comes after a 2-year review of the company’s application seeking authorization to continue selling non–fruit-flavored products, such as menthol and tobacco. The FDA determined the application “lacked sufficient evidence regarding the toxicological profile of the products to demonstrate that marketing of the products would be appropriate for the protection of the public health.”

Some of Juul’s study findings raised concerns because of “insufficient and conflicting data,” the FDA said, including potentially harmful chemicals leaching from the Juul liquid replacement pods.

“To date, the FDA has not received clinical information to suggest an immediate hazard associated with the use of the JUUL device or JUUL pods,” the agency said. “However, the [orders] issued today reflect FDA’s determination that there is insufficient evidence to assess the potential toxicological risks of using the JUUL products.”

Juul is expected to appeal the FDA’s decision, according to The New York Times.

In recent years, the FDA has reviewed marketing applications from Juul and other e-cigarette companies as anti-tobacco groups have called for new rules to limit products that led to a surge in youth vaping during the past decade. At the same time, advocates of e-cigarettes and nicotine-delivery devices have said the products help adult smokers to quit cigarettes and other tobacco products.

Juul, in particular, has been blamed for fueling the surge in underage vaping due to fruity flavors and hip marketing, according to The Wall Street Journal. The company removed sweet and fruity flavors from shelves in 2019 and has been trying to repair its reputation by limiting its marketing and focusing on adult cigarette smokers.

In 2020, all e-cigarette manufacturers in the United States were required to submit their products for FDA review to stay on the market, the newspaper reported. The agency has been weighing the potential benefits for adult cigarette smokers against the harms for young people.

The FDA banned the sale of fruit- and mint-flavored cartridges and juice pods in 2020, but menthol and tobacco-flavored products were left on the market, according to USA Today. In September 2021, the agency also banned the sale of hundreds of thousands of vaping and e-cigarette products but didn’t rule on Juul.

Meanwhile, the FDA has cleared Reynolds American and NJOY Holdings – two of Juul’s biggest rivals – to keep tobacco-flavored products on the market. Industry experts expected Juul to receive similar clearance, the Journal reported.

Juul, which was at the top of the U.S. e-cigarette market in 2018, has moved to second place behind Reynolds’s Vuse brand, the newspaper reported. The United States represents most of the company’s revenue, though its products are also available in Canada, the United Kingdom, France, Italy, and the Philippines.

Underage vaping has fallen in the United States since federal restrictions raised the legal purchase age for tobacco products to 21 and banned the sale of sweet and fruity cartridges, according to the Journal. Juul’s popularity has also dropped among youth, with other products such as Puff Bar, Vuse, and Smok becoming more popular among e-cigarette users in high school.

In a separate decision announced this week, the FDA is also moving forward with a plan to reduce the amount of nicotine in cigarettes. The decision, which has been years in the making, is aimed at prompting millions of cigarette users to quit smoking or switch to alternatives such as e-cigarettes, as well as limit the number of users who pick up smoking at an early age.

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

The Food and Drug Administration has ordered Juul Labs to stop selling e-cigarettes and vaping products on the U.S. market, the agency announced June 23.

The marketing denial order covers all the company’s products in the United States, which means Juul must stop distributing the products and remove everything on the market. That includes the Juul device and flavor replacement pods in the tobacco and menthol flavors.

“Today’s action is further progress on the FDA’s commitment to ensuring that all e-cigarette and electronic nicotine delivery system products currently being marketed to consumers meet our public health standards,” Robert Califf, MD, the FDA commissioner, said in the announcement.

“The agency has dedicated significant resources to review products from the companies that account for most of the U.S. market,” he said. “We recognize these make up a significant part of the available products and many have played a disproportionate role in the rise in youth vaping.”

The marketing denial order covers only the commercial distribution and retail sale of Juul’s products and doesn’t restrict consumer possession or use. The FDA “cannot and will not” enforce actions against consumers, the agency said.

The order comes after a 2-year review of the company’s application seeking authorization to continue selling non–fruit-flavored products, such as menthol and tobacco. The FDA determined the application “lacked sufficient evidence regarding the toxicological profile of the products to demonstrate that marketing of the products would be appropriate for the protection of the public health.”

Some of Juul’s study findings raised concerns because of “insufficient and conflicting data,” the FDA said, including potentially harmful chemicals leaching from the Juul liquid replacement pods.

“To date, the FDA has not received clinical information to suggest an immediate hazard associated with the use of the JUUL device or JUUL pods,” the agency said. “However, the [orders] issued today reflect FDA’s determination that there is insufficient evidence to assess the potential toxicological risks of using the JUUL products.”

Juul is expected to appeal the FDA’s decision, according to The New York Times.

In recent years, the FDA has reviewed marketing applications from Juul and other e-cigarette companies as anti-tobacco groups have called for new rules to limit products that led to a surge in youth vaping during the past decade. At the same time, advocates of e-cigarettes and nicotine-delivery devices have said the products help adult smokers to quit cigarettes and other tobacco products.

Juul, in particular, has been blamed for fueling the surge in underage vaping due to fruity flavors and hip marketing, according to The Wall Street Journal. The company removed sweet and fruity flavors from shelves in 2019 and has been trying to repair its reputation by limiting its marketing and focusing on adult cigarette smokers.

In 2020, all e-cigarette manufacturers in the United States were required to submit their products for FDA review to stay on the market, the newspaper reported. The agency has been weighing the potential benefits for adult cigarette smokers against the harms for young people.

The FDA banned the sale of fruit- and mint-flavored cartridges and juice pods in 2020, but menthol and tobacco-flavored products were left on the market, according to USA Today. In September 2021, the agency also banned the sale of hundreds of thousands of vaping and e-cigarette products but didn’t rule on Juul.

Meanwhile, the FDA has cleared Reynolds American and NJOY Holdings – two of Juul’s biggest rivals – to keep tobacco-flavored products on the market. Industry experts expected Juul to receive similar clearance, the Journal reported.

Juul, which was at the top of the U.S. e-cigarette market in 2018, has moved to second place behind Reynolds’s Vuse brand, the newspaper reported. The United States represents most of the company’s revenue, though its products are also available in Canada, the United Kingdom, France, Italy, and the Philippines.

Underage vaping has fallen in the United States since federal restrictions raised the legal purchase age for tobacco products to 21 and banned the sale of sweet and fruity cartridges, according to the Journal. Juul’s popularity has also dropped among youth, with other products such as Puff Bar, Vuse, and Smok becoming more popular among e-cigarette users in high school.

In a separate decision announced this week, the FDA is also moving forward with a plan to reduce the amount of nicotine in cigarettes. The decision, which has been years in the making, is aimed at prompting millions of cigarette users to quit smoking or switch to alternatives such as e-cigarettes, as well as limit the number of users who pick up smoking at an early age.

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

The Food and Drug Administration has ordered Juul Labs to stop selling e-cigarettes and vaping products on the U.S. market, the agency announced June 23.

The marketing denial order covers all the company’s products in the United States, which means Juul must stop distributing the products and remove everything on the market. That includes the Juul device and flavor replacement pods in the tobacco and menthol flavors.

“Today’s action is further progress on the FDA’s commitment to ensuring that all e-cigarette and electronic nicotine delivery system products currently being marketed to consumers meet our public health standards,” Robert Califf, MD, the FDA commissioner, said in the announcement.

“The agency has dedicated significant resources to review products from the companies that account for most of the U.S. market,” he said. “We recognize these make up a significant part of the available products and many have played a disproportionate role in the rise in youth vaping.”

The marketing denial order covers only the commercial distribution and retail sale of Juul’s products and doesn’t restrict consumer possession or use. The FDA “cannot and will not” enforce actions against consumers, the agency said.

The order comes after a 2-year review of the company’s application seeking authorization to continue selling non–fruit-flavored products, such as menthol and tobacco. The FDA determined the application “lacked sufficient evidence regarding the toxicological profile of the products to demonstrate that marketing of the products would be appropriate for the protection of the public health.”

Some of Juul’s study findings raised concerns because of “insufficient and conflicting data,” the FDA said, including potentially harmful chemicals leaching from the Juul liquid replacement pods.

“To date, the FDA has not received clinical information to suggest an immediate hazard associated with the use of the JUUL device or JUUL pods,” the agency said. “However, the [orders] issued today reflect FDA’s determination that there is insufficient evidence to assess the potential toxicological risks of using the JUUL products.”

Juul is expected to appeal the FDA’s decision, according to The New York Times.

In recent years, the FDA has reviewed marketing applications from Juul and other e-cigarette companies as anti-tobacco groups have called for new rules to limit products that led to a surge in youth vaping during the past decade. At the same time, advocates of e-cigarettes and nicotine-delivery devices have said the products help adult smokers to quit cigarettes and other tobacco products.

Juul, in particular, has been blamed for fueling the surge in underage vaping due to fruity flavors and hip marketing, according to The Wall Street Journal. The company removed sweet and fruity flavors from shelves in 2019 and has been trying to repair its reputation by limiting its marketing and focusing on adult cigarette smokers.

In 2020, all e-cigarette manufacturers in the United States were required to submit their products for FDA review to stay on the market, the newspaper reported. The agency has been weighing the potential benefits for adult cigarette smokers against the harms for young people.

The FDA banned the sale of fruit- and mint-flavored cartridges and juice pods in 2020, but menthol and tobacco-flavored products were left on the market, according to USA Today. In September 2021, the agency also banned the sale of hundreds of thousands of vaping and e-cigarette products but didn’t rule on Juul.

Meanwhile, the FDA has cleared Reynolds American and NJOY Holdings – two of Juul’s biggest rivals – to keep tobacco-flavored products on the market. Industry experts expected Juul to receive similar clearance, the Journal reported.

Juul, which was at the top of the U.S. e-cigarette market in 2018, has moved to second place behind Reynolds’s Vuse brand, the newspaper reported. The United States represents most of the company’s revenue, though its products are also available in Canada, the United Kingdom, France, Italy, and the Philippines.

Underage vaping has fallen in the United States since federal restrictions raised the legal purchase age for tobacco products to 21 and banned the sale of sweet and fruity cartridges, according to the Journal. Juul’s popularity has also dropped among youth, with other products such as Puff Bar, Vuse, and Smok becoming more popular among e-cigarette users in high school.

In a separate decision announced this week, the FDA is also moving forward with a plan to reduce the amount of nicotine in cigarettes. The decision, which has been years in the making, is aimed at prompting millions of cigarette users to quit smoking or switch to alternatives such as e-cigarettes, as well as limit the number of users who pick up smoking at an early age.

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

Thanks to effective treatment, people with HIV are living longer. But as they age, they face higher rates of age-related comorbidities and hospitalizations, according to a recent study of hospitalized patients.

Decision-makers will need to allocate resources, train providers, and plan ways to manage chronic diseases, such as diabetes and cancer, among geriatric HIV inpatients, according to the authors.

“There will be more [HIV] patients with age-related chronic conditions at an earlier age and who will utilize or will have a unique need for [health care for] these geriatric conditions,” first author Khairul A. Siddiqi, PhD, University of Florida, Gainesville, said in an interview. “Eventually, that may increase inpatient resource utilization and costs.”

The study was published online in HIV Medicine.
 

Aging with HIV

Analyzing the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project, the authors compared characteristics and comorbidities linked to hospital stays among people with HIV (HSWH) to those linked to hospital stays among people without HIV (HSWOH).

The NIS is a database of hospital records that captures 20% of discharges in the United States and covers all payers. Data in this analysis covered the years 2003-2015.

Among HSWH, patients aged 50 or older accounted for an increasing proportion over time, from fewer than 25% in 2003 to over 50% by 2015, the authors found. The subgroup aged 65-80 had risen from 2.39% to 8.63% by 2015.

The authors also studied rates of eight comorbidities, termed HIV-associated non-AIDS (HANA) conditions: cardiovascular, lung, liver, neurologic, and kidney diseases; diabetes; cancer; and bone loss.

The average number of these conditions among both HSWH and HSWOH rose over time. But this change was disproportionately high among HSWH aged 50-64 and those aged 65 and older.

Over the study period, among patients aged 65 or older, six of the eight age-related conditions the researchers studied rose disproportionately among HSWH in comparison with HSWOH; among those aged 50-64, five conditions did so.

The researchers are now building on the current study of HSWH by examining rates of resource utilization, such as MRIs and procedures, Dr. Siddiqi said.

Study limitations included a lack of data from long-term facilities, potential skewing by patients hospitalized multiple times, and the inherent limitations of administrative data.
 

A unique group of older people

Among people with HIV (PWH) in the United States, nearly half are aged 50 or older. By 2030, this group is expected to account for some 70% of PWH.

“We need to pay attention to what we know about aging generally. It is also important to study aging in this special population, because we don’t necessarily know a lot about that,” Amy Justice, MD, PhD, professor of medicine and of public health at Yale University, New Haven, Conn., said in an interview. Dr. Justice was not involved in the study.

The HIV epidemic has disproportionately affected people of color, men who have sex with men, and people with a history of injection drug use, Dr. Justice said.

“We don’t know about aging with [a] past history of injection drug use. We don’t even know much about aging with hepatitis C, necessarily,” she said. “So there are lots of reasons to pay some attention to this population to try to optimize their care.”

In addition, compared with their non–HIV-affected counterparts, these individuals are more susceptible to HANA comorbidities. They may experience these conditions at a younger age or more severely. Chronic inflammation and polypharmacy may be to blame, said Dr. Justice.

Given the burden of comorbidities and polypharmacy in this patient population, Dr. Siddiqi said, policy makers will need to focus on developing chronic disease management interventions for them.

However, Dr. Justice added, the risk for multimorbidity is higher among people with HIV throughout the age cycle: “It’s not like I turn 50 with HIV and all of a sudden all the wheels come off. There are ways to successfully age with HIV.”
 

Geriatric HIV expertise needed

Dr. Justice called the study’s analysis a useful addition to the literature and noted its implications for training.

“One of the biggest challenges with this large bolus of folks who are aging with HIV,” she said, “is to what extent should they be cared for by the people who have been caring for them – largely infectious disease docs – and to what extent should we really be transitioning their care to people with more experience with aging.”

Another key question, Dr. Justice said, relates to nursing homes and assisted-living facilities, whose staff may lack experience caring for HIV patients. Training them and hospital-based providers is crucial, in part to avoid key errors, such as missed antiretroviral doses, she said: “We need to really think about how to get non-HIV providers up to speed.”

That may begin by simply making it clear that this population is here.

“A decade ago, HIV patients used to have a lower life expectancy, so all HIV studies used to use 50 years as the cutoff point for [the] older population,” Dr. Siddiqi said. “Now we know they’re living longer.”

Added Dr. Justice: “Previously, people thought aging and HIV were not coincident findings.”

The study was funded by the Office of the Vice President for Research at the University of South Carolina. The authors and Dr. Justice disclosed no relevant financial relationships.

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

Thanks to effective treatment, people with HIV are living longer. But as they age, they face higher rates of age-related comorbidities and hospitalizations, according to a recent study of hospitalized patients.

Decision-makers will need to allocate resources, train providers, and plan ways to manage chronic diseases, such as diabetes and cancer, among geriatric HIV inpatients, according to the authors.

“There will be more [HIV] patients with age-related chronic conditions at an earlier age and who will utilize or will have a unique need for [health care for] these geriatric conditions,” first author Khairul A. Siddiqi, PhD, University of Florida, Gainesville, said in an interview. “Eventually, that may increase inpatient resource utilization and costs.”

The study was published online in HIV Medicine.
 

Aging with HIV

Analyzing the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project, the authors compared characteristics and comorbidities linked to hospital stays among people with HIV (HSWH) to those linked to hospital stays among people without HIV (HSWOH).

The NIS is a database of hospital records that captures 20% of discharges in the United States and covers all payers. Data in this analysis covered the years 2003-2015.

Among HSWH, patients aged 50 or older accounted for an increasing proportion over time, from fewer than 25% in 2003 to over 50% by 2015, the authors found. The subgroup aged 65-80 had risen from 2.39% to 8.63% by 2015.

The authors also studied rates of eight comorbidities, termed HIV-associated non-AIDS (HANA) conditions: cardiovascular, lung, liver, neurologic, and kidney diseases; diabetes; cancer; and bone loss.

The average number of these conditions among both HSWH and HSWOH rose over time. But this change was disproportionately high among HSWH aged 50-64 and those aged 65 and older.

Over the study period, among patients aged 65 or older, six of the eight age-related conditions the researchers studied rose disproportionately among HSWH in comparison with HSWOH; among those aged 50-64, five conditions did so.

The researchers are now building on the current study of HSWH by examining rates of resource utilization, such as MRIs and procedures, Dr. Siddiqi said.

Study limitations included a lack of data from long-term facilities, potential skewing by patients hospitalized multiple times, and the inherent limitations of administrative data.
 

A unique group of older people

Among people with HIV (PWH) in the United States, nearly half are aged 50 or older. By 2030, this group is expected to account for some 70% of PWH.

“We need to pay attention to what we know about aging generally. It is also important to study aging in this special population, because we don’t necessarily know a lot about that,” Amy Justice, MD, PhD, professor of medicine and of public health at Yale University, New Haven, Conn., said in an interview. Dr. Justice was not involved in the study.

The HIV epidemic has disproportionately affected people of color, men who have sex with men, and people with a history of injection drug use, Dr. Justice said.

“We don’t know about aging with [a] past history of injection drug use. We don’t even know much about aging with hepatitis C, necessarily,” she said. “So there are lots of reasons to pay some attention to this population to try to optimize their care.”

In addition, compared with their non–HIV-affected counterparts, these individuals are more susceptible to HANA comorbidities. They may experience these conditions at a younger age or more severely. Chronic inflammation and polypharmacy may be to blame, said Dr. Justice.

Given the burden of comorbidities and polypharmacy in this patient population, Dr. Siddiqi said, policy makers will need to focus on developing chronic disease management interventions for them.

However, Dr. Justice added, the risk for multimorbidity is higher among people with HIV throughout the age cycle: “It’s not like I turn 50 with HIV and all of a sudden all the wheels come off. There are ways to successfully age with HIV.”
 

Geriatric HIV expertise needed

Dr. Justice called the study’s analysis a useful addition to the literature and noted its implications for training.

“One of the biggest challenges with this large bolus of folks who are aging with HIV,” she said, “is to what extent should they be cared for by the people who have been caring for them – largely infectious disease docs – and to what extent should we really be transitioning their care to people with more experience with aging.”

Another key question, Dr. Justice said, relates to nursing homes and assisted-living facilities, whose staff may lack experience caring for HIV patients. Training them and hospital-based providers is crucial, in part to avoid key errors, such as missed antiretroviral doses, she said: “We need to really think about how to get non-HIV providers up to speed.”

That may begin by simply making it clear that this population is here.

“A decade ago, HIV patients used to have a lower life expectancy, so all HIV studies used to use 50 years as the cutoff point for [the] older population,” Dr. Siddiqi said. “Now we know they’re living longer.”

Added Dr. Justice: “Previously, people thought aging and HIV were not coincident findings.”

The study was funded by the Office of the Vice President for Research at the University of South Carolina. The authors and Dr. Justice disclosed no relevant financial relationships.

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

Thanks to effective treatment, people with HIV are living longer. But as they age, they face higher rates of age-related comorbidities and hospitalizations, according to a recent study of hospitalized patients.

Decision-makers will need to allocate resources, train providers, and plan ways to manage chronic diseases, such as diabetes and cancer, among geriatric HIV inpatients, according to the authors.

“There will be more [HIV] patients with age-related chronic conditions at an earlier age and who will utilize or will have a unique need for [health care for] these geriatric conditions,” first author Khairul A. Siddiqi, PhD, University of Florida, Gainesville, said in an interview. “Eventually, that may increase inpatient resource utilization and costs.”

The study was published online in HIV Medicine.
 

Aging with HIV

Analyzing the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project, the authors compared characteristics and comorbidities linked to hospital stays among people with HIV (HSWH) to those linked to hospital stays among people without HIV (HSWOH).

The NIS is a database of hospital records that captures 20% of discharges in the United States and covers all payers. Data in this analysis covered the years 2003-2015.

Among HSWH, patients aged 50 or older accounted for an increasing proportion over time, from fewer than 25% in 2003 to over 50% by 2015, the authors found. The subgroup aged 65-80 had risen from 2.39% to 8.63% by 2015.

The authors also studied rates of eight comorbidities, termed HIV-associated non-AIDS (HANA) conditions: cardiovascular, lung, liver, neurologic, and kidney diseases; diabetes; cancer; and bone loss.

The average number of these conditions among both HSWH and HSWOH rose over time. But this change was disproportionately high among HSWH aged 50-64 and those aged 65 and older.

Over the study period, among patients aged 65 or older, six of the eight age-related conditions the researchers studied rose disproportionately among HSWH in comparison with HSWOH; among those aged 50-64, five conditions did so.

The researchers are now building on the current study of HSWH by examining rates of resource utilization, such as MRIs and procedures, Dr. Siddiqi said.

Study limitations included a lack of data from long-term facilities, potential skewing by patients hospitalized multiple times, and the inherent limitations of administrative data.
 

A unique group of older people

Among people with HIV (PWH) in the United States, nearly half are aged 50 or older. By 2030, this group is expected to account for some 70% of PWH.

“We need to pay attention to what we know about aging generally. It is also important to study aging in this special population, because we don’t necessarily know a lot about that,” Amy Justice, MD, PhD, professor of medicine and of public health at Yale University, New Haven, Conn., said in an interview. Dr. Justice was not involved in the study.

The HIV epidemic has disproportionately affected people of color, men who have sex with men, and people with a history of injection drug use, Dr. Justice said.

“We don’t know about aging with [a] past history of injection drug use. We don’t even know much about aging with hepatitis C, necessarily,” she said. “So there are lots of reasons to pay some attention to this population to try to optimize their care.”

In addition, compared with their non–HIV-affected counterparts, these individuals are more susceptible to HANA comorbidities. They may experience these conditions at a younger age or more severely. Chronic inflammation and polypharmacy may be to blame, said Dr. Justice.

Given the burden of comorbidities and polypharmacy in this patient population, Dr. Siddiqi said, policy makers will need to focus on developing chronic disease management interventions for them.

However, Dr. Justice added, the risk for multimorbidity is higher among people with HIV throughout the age cycle: “It’s not like I turn 50 with HIV and all of a sudden all the wheels come off. There are ways to successfully age with HIV.”
 

Geriatric HIV expertise needed

Dr. Justice called the study’s analysis a useful addition to the literature and noted its implications for training.

“One of the biggest challenges with this large bolus of folks who are aging with HIV,” she said, “is to what extent should they be cared for by the people who have been caring for them – largely infectious disease docs – and to what extent should we really be transitioning their care to people with more experience with aging.”

Another key question, Dr. Justice said, relates to nursing homes and assisted-living facilities, whose staff may lack experience caring for HIV patients. Training them and hospital-based providers is crucial, in part to avoid key errors, such as missed antiretroviral doses, she said: “We need to really think about how to get non-HIV providers up to speed.”

That may begin by simply making it clear that this population is here.

“A decade ago, HIV patients used to have a lower life expectancy, so all HIV studies used to use 50 years as the cutoff point for [the] older population,” Dr. Siddiqi said. “Now we know they’re living longer.”

Added Dr. Justice: “Previously, people thought aging and HIV were not coincident findings.”

The study was funded by the Office of the Vice President for Research at the University of South Carolina. The authors and Dr. Justice disclosed no relevant financial relationships.

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

DENVER – Monoclonal antibodies, antivirals, immunomodulators, and pulmonary arterial vasodilators top the list of drugs that were most frequently implicated as causes of headaches in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.

“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.

Drugs most frequently linked to headaches

The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”

After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.

The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).

Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.

“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
 

Is the data useful?

Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.

“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”

When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.

No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
 

DENVER – Monoclonal antibodies, antivirals, immunomodulators, and pulmonary arterial vasodilators top the list of drugs that were most frequently implicated as causes of headaches in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.

“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.

Drugs most frequently linked to headaches

The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”

After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.

The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).

Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.

“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
 

Is the data useful?

Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.

“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”

When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.

No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
 

DENVER – Monoclonal antibodies, antivirals, immunomodulators, and pulmonary arterial vasodilators top the list of drugs that were most frequently implicated as causes of headaches in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.

“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.

Drugs most frequently linked to headaches

The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”

After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.

The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).

Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.

“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
 

Is the data useful?

Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.

“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”

When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.

No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
 

Human papilloma virus (HPV) vaccination coverage of at least one dose significantly increased in U.S. adolescents from 56.1% in 2015 to 75.4% in 2020, according to the National Immunization Survey–Teen (NIS-Teen).

The telephone survey, conducted among the parents or guardians of children ages 13-17, found a faster increase in coverage among males than females: 4.7 percentage points annually versus 2.7 percentage points annually. With yearly overall survey samples ranging from 21,875 to 17,970, these coverage differences between males and females narrowed over the 5 years of the survey period.

The difference between coverage among males and females decreased from 13 to 3 percentage points. Traditionally, parents of boys have been less likely to vaccinate their sons against HPV.

Despite the increase in uptake, however, in 2020 about 25% of adolescents had not received at least one dose of HPV vaccine. “Targeted strategies are needed to increase coverage and narrow down inequalities,” Peng-jun Lu, MD, PhD, of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention in Atlanta, and colleagues wrote in Pediatrics.

In other NIS-Teen findings:

• Coverage in 2020 was 73.7% for males and 76.8% for females (P < .05).
• Coverage rose to 80.7% for those with a provider recommendation but was only 51.7% for those without one (P < .05).
• The rate was 80.3% for those with a well-child visit at age 11-12 years and 64.8% for those without (P < .05).
• In multivariable logistic regression, the main characteristics independently associated with a higher likelihood of vaccination included a provider recommendation, age 16-17 years, and being non-Hispanic Black, Hispanic, American Indian, or Alaskan Native.
• Other predictors of vaccination included having Medicaid insurance and having a mother who was widowed, divorced, or separated, or had no more than a high school education.
• Also predictive was having two or more provider contacts in the past 12 months, a well-child visit at age 11-12 years, and one or two vaccine providers (P < .05).
• Coverage among adolescents living in non-metropolitan statistical areas was significantly lower than those living in MSA principal cities in all years assessed (P < .05).

Provider recommendation remains significant and has historically been highly associated with HPV vaccination. In the 2012 NIS-Teen, for example, 15% of parents not intending to have their daughters vaccinated in the next 12 months cited the lack of a provider recommendation.

“To increase HPV vaccination coverage and further reduce HPV-related morbidity and mortality, providers, parents, and adolescents should use every health care visit as a chance to review vaccination histories and ensure that every adolescent receives the HPV vaccine and other needed vaccines,” Dr. Lu and associates wrote. But 18.5% of parents in the survey received no provider recommendation.

“Of note, we found that teenagers who had mothers with more education or who live in more rural communities had a lower likelihood of receiving vaccination against HPV,” Dr. Lu told this news organization. “Further research should be conducted to better understand these findings.”

According to Margaret E. Thew, DNP, FNP-BC, director of adolescent medicine at the Medical College of Wisconsin in Milwaukee, several studies have highlighted resistance to the vaccine among better-educated parents. “Parents with higher education associate the HPV vaccine with sexual activity and consequently refuse,” said Ms. Thew, who was not involved in the NIS-Teen study. “They mistakenly assume that their children are not sexually active and they lack the understanding that HPV is one of the biggest causes of oral cancer.”

Human papilloma virus (HPV) vaccination coverage of at least one dose significantly increased in U.S. adolescents from 56.1% in 2015 to 75.4% in 2020, according to the National Immunization Survey–Teen (NIS-Teen).

The telephone survey, conducted among the parents or guardians of children ages 13-17, found a faster increase in coverage among males than females: 4.7 percentage points annually versus 2.7 percentage points annually. With yearly overall survey samples ranging from 21,875 to 17,970, these coverage differences between males and females narrowed over the 5 years of the survey period.

The difference between coverage among males and females decreased from 13 to 3 percentage points. Traditionally, parents of boys have been less likely to vaccinate their sons against HPV.

Despite the increase in uptake, however, in 2020 about 25% of adolescents had not received at least one dose of HPV vaccine. “Targeted strategies are needed to increase coverage and narrow down inequalities,” Peng-jun Lu, MD, PhD, of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention in Atlanta, and colleagues wrote in Pediatrics.

In other NIS-Teen findings:

• Coverage in 2020 was 73.7% for males and 76.8% for females (P < .05).
• Coverage rose to 80.7% for those with a provider recommendation but was only 51.7% for those without one (P < .05).
• The rate was 80.3% for those with a well-child visit at age 11-12 years and 64.8% for those without (P < .05).
• In multivariable logistic regression, the main characteristics independently associated with a higher likelihood of vaccination included a provider recommendation, age 16-17 years, and being non-Hispanic Black, Hispanic, American Indian, or Alaskan Native.
• Other predictors of vaccination included having Medicaid insurance and having a mother who was widowed, divorced, or separated, or had no more than a high school education.
• Also predictive was having two or more provider contacts in the past 12 months, a well-child visit at age 11-12 years, and one or two vaccine providers (P < .05).
• Coverage among adolescents living in non-metropolitan statistical areas was significantly lower than those living in MSA principal cities in all years assessed (P < .05).

Provider recommendation remains significant and has historically been highly associated with HPV vaccination. In the 2012 NIS-Teen, for example, 15% of parents not intending to have their daughters vaccinated in the next 12 months cited the lack of a provider recommendation.

“To increase HPV vaccination coverage and further reduce HPV-related morbidity and mortality, providers, parents, and adolescents should use every health care visit as a chance to review vaccination histories and ensure that every adolescent receives the HPV vaccine and other needed vaccines,” Dr. Lu and associates wrote. But 18.5% of parents in the survey received no provider recommendation.

“Of note, we found that teenagers who had mothers with more education or who live in more rural communities had a lower likelihood of receiving vaccination against HPV,” Dr. Lu told this news organization. “Further research should be conducted to better understand these findings.”

According to Margaret E. Thew, DNP, FNP-BC, director of adolescent medicine at the Medical College of Wisconsin in Milwaukee, several studies have highlighted resistance to the vaccine among better-educated parents. “Parents with higher education associate the HPV vaccine with sexual activity and consequently refuse,” said Ms. Thew, who was not involved in the NIS-Teen study. “They mistakenly assume that their children are not sexually active and they lack the understanding that HPV is one of the biggest causes of oral cancer.”

Human papilloma virus (HPV) vaccination coverage of at least one dose significantly increased in U.S. adolescents from 56.1% in 2015 to 75.4% in 2020, according to the National Immunization Survey–Teen (NIS-Teen).

The telephone survey, conducted among the parents or guardians of children ages 13-17, found a faster increase in coverage among males than females: 4.7 percentage points annually versus 2.7 percentage points annually. With yearly overall survey samples ranging from 21,875 to 17,970, these coverage differences between males and females narrowed over the 5 years of the survey period.

The difference between coverage among males and females decreased from 13 to 3 percentage points. Traditionally, parents of boys have been less likely to vaccinate their sons against HPV.

Despite the increase in uptake, however, in 2020 about 25% of adolescents had not received at least one dose of HPV vaccine. “Targeted strategies are needed to increase coverage and narrow down inequalities,” Peng-jun Lu, MD, PhD, of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention in Atlanta, and colleagues wrote in Pediatrics.

In other NIS-Teen findings:

• Coverage in 2020 was 73.7% for males and 76.8% for females (P < .05).
• Coverage rose to 80.7% for those with a provider recommendation but was only 51.7% for those without one (P < .05).
• The rate was 80.3% for those with a well-child visit at age 11-12 years and 64.8% for those without (P < .05).
• In multivariable logistic regression, the main characteristics independently associated with a higher likelihood of vaccination included a provider recommendation, age 16-17 years, and being non-Hispanic Black, Hispanic, American Indian, or Alaskan Native.
• Other predictors of vaccination included having Medicaid insurance and having a mother who was widowed, divorced, or separated, or had no more than a high school education.
• Also predictive was having two or more provider contacts in the past 12 months, a well-child visit at age 11-12 years, and one or two vaccine providers (P < .05).
• Coverage among adolescents living in non-metropolitan statistical areas was significantly lower than those living in MSA principal cities in all years assessed (P < .05).

Provider recommendation remains significant and has historically been highly associated with HPV vaccination. In the 2012 NIS-Teen, for example, 15% of parents not intending to have their daughters vaccinated in the next 12 months cited the lack of a provider recommendation.

“To increase HPV vaccination coverage and further reduce HPV-related morbidity and mortality, providers, parents, and adolescents should use every health care visit as a chance to review vaccination histories and ensure that every adolescent receives the HPV vaccine and other needed vaccines,” Dr. Lu and associates wrote. But 18.5% of parents in the survey received no provider recommendation.

“Of note, we found that teenagers who had mothers with more education or who live in more rural communities had a lower likelihood of receiving vaccination against HPV,” Dr. Lu told this news organization. “Further research should be conducted to better understand these findings.”

According to Margaret E. Thew, DNP, FNP-BC, director of adolescent medicine at the Medical College of Wisconsin in Milwaukee, several studies have highlighted resistance to the vaccine among better-educated parents. “Parents with higher education associate the HPV vaccine with sexual activity and consequently refuse,” said Ms. Thew, who was not involved in the NIS-Teen study. “They mistakenly assume that their children are not sexually active and they lack the understanding that HPV is one of the biggest causes of oral cancer.”

For generally healthy patients taking isotretinoin for acne and who have no underlying abnormalities or preexisting conditions that warrant further examination, it is sufficient to test ALT and triglycerides once at baseline, ideally within a month prior to the start of treatment, and a second time at peak dose.

Other tests such as complete blood cell counts and basic metabolic panels as well as specific laboratory tests such as LDL and HDL cholesterol should not be routinely monitored.

Those are key conclusions from a Delphi consensus study that included 22 acne experts from five continents and was published in JAMA Dermatology.

“Our results apply findings from recent literature and are in accordance with recent studies that have recommended against excessive laboratory monitoring,” senior corresponding author Arash Mostaghimi, MD, MPA, MPH, and coauthors wrote. “For instance, several studies in both teenagers and adults have shown that routine complete blood cell count laboratory tests are unnecessary without suspicion of an underlying abnormality and that rare abnormalities, if present, either resolved or remained stable without clinical impact on treatment. Likewise, liver function tests and lipid panels ordered at baseline and after 2 months of therapy were deemed sufficient if the clinical context and results do not suggest potential abnormalities.”

The authors also noted that, while published acne management guidelines exist, such as the American Academy of Dermatology work group guidelines and the National Institute for Health and Care Excellence guideline, “the specific recommendations surrounding laboratory monitoring frequency are nonstandardized and often nonspecific.”

To establish a consensus for isotretinoin laboratory monitoring, Dr. Mostaghimi, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to administer four rounds of electronic surveys to 22 board-certified dermatologists between 2021 and 2022. The primary outcome measured was whether participants could reach consensus on key isotretinoin lab monitoring parameters. Responses that failed to reach a threshold of 70% indicated no consensus.

The surveyed dermatologists had been in practice for a mean of 23.7 years, 54.5% were female, 54.5% practiced in an academic setting, and 63.9% were based in North America. They reached consensus for checking ALT within a month prior to initiation (89.5%) and at peak dose (89.5%), but not checking monthly (76.2%) or after completing treatment (73.7%). They also reached consensus on checking triglycerides within a month prior to initiation (89.5%) and at peak dose (78.9%) but not to check monthly (84.2%) or after completing treatment (73.7%).

Meanwhile, consensus was achieved for not checking complete blood cell count or basic metabolic panel parameters at any point during isotretinoin treatment (all > 70%), as well as not checking gamma-glutamyl transferase (78.9%), bilirubin (81.0%), albumin (72.7%), total protein (72.7%), LDL cholesterol (73.7%), HDL cholesterol (73.7%), or C-reactive protein (77.3%).

“Additional research is required to determine best practices for laboratory measures that did not reach consensus,” the authors wrote. The study results “are intended to guide appropriate clinical decision-making,” they added. “Although our recommendations cannot replace clinical judgment based on the unique circumstances of individual patients, we believe they provide a framework for management of a typical, otherwise healthy patient being treated with isotretinoin for acne. More routine monitoring, or reduced monitoring, should be considered on a case-by-case basis accounting for the unique medical history, circumstances, and baseline abnormalities, if present, of each patient.”

“Practicing dermatologists, including myself, routinely check blood laboratory values during isotretinoin treatment,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “Even though just a small number of U.S.-based and international acne researchers were involved in this Delphi consensus statement, this article still makes us practicing clinicians feel more comfortable in checking fewer lab chemistries and also less frequently checking labs when we use isotretinoin.

“That said, I don’t think most of us are ready, because of legal reasons, to do that infrequent monitoring” during isotretinoin therapy, Dr. Green added. “I think most dermatologists do not routinely perform CBCs anymore, but we still feel obligated to check triglycerides and liver function more frequently” than recommended in the new study.

Dr. Mostaghimi reported receiving grants and personal fees from Pfizer, personal fees from Eli Lilly, personal fees and licensing from Concert, personal fees from Bioniz, holds equity and advisory board membership from Hims & Hers and Figure 1, personal fees from Digital Diagnostics, and personal fees from AbbVie outside the submitted work. Other authors reported serving as an adviser, a speaker consultant, investigator, and/or board member, or having received honoraria from different pharmaceutical companies; several authors had no disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

For generally healthy patients taking isotretinoin for acne and who have no underlying abnormalities or preexisting conditions that warrant further examination, it is sufficient to test ALT and triglycerides once at baseline, ideally within a month prior to the start of treatment, and a second time at peak dose.

Other tests such as complete blood cell counts and basic metabolic panels as well as specific laboratory tests such as LDL and HDL cholesterol should not be routinely monitored.

Those are key conclusions from a Delphi consensus study that included 22 acne experts from five continents and was published in JAMA Dermatology.

“Our results apply findings from recent literature and are in accordance with recent studies that have recommended against excessive laboratory monitoring,” senior corresponding author Arash Mostaghimi, MD, MPA, MPH, and coauthors wrote. “For instance, several studies in both teenagers and adults have shown that routine complete blood cell count laboratory tests are unnecessary without suspicion of an underlying abnormality and that rare abnormalities, if present, either resolved or remained stable without clinical impact on treatment. Likewise, liver function tests and lipid panels ordered at baseline and after 2 months of therapy were deemed sufficient if the clinical context and results do not suggest potential abnormalities.”

The authors also noted that, while published acne management guidelines exist, such as the American Academy of Dermatology work group guidelines and the National Institute for Health and Care Excellence guideline, “the specific recommendations surrounding laboratory monitoring frequency are nonstandardized and often nonspecific.”

To establish a consensus for isotretinoin laboratory monitoring, Dr. Mostaghimi, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to administer four rounds of electronic surveys to 22 board-certified dermatologists between 2021 and 2022. The primary outcome measured was whether participants could reach consensus on key isotretinoin lab monitoring parameters. Responses that failed to reach a threshold of 70% indicated no consensus.

The surveyed dermatologists had been in practice for a mean of 23.7 years, 54.5% were female, 54.5% practiced in an academic setting, and 63.9% were based in North America. They reached consensus for checking ALT within a month prior to initiation (89.5%) and at peak dose (89.5%), but not checking monthly (76.2%) or after completing treatment (73.7%). They also reached consensus on checking triglycerides within a month prior to initiation (89.5%) and at peak dose (78.9%) but not to check monthly (84.2%) or after completing treatment (73.7%).

Meanwhile, consensus was achieved for not checking complete blood cell count or basic metabolic panel parameters at any point during isotretinoin treatment (all > 70%), as well as not checking gamma-glutamyl transferase (78.9%), bilirubin (81.0%), albumin (72.7%), total protein (72.7%), LDL cholesterol (73.7%), HDL cholesterol (73.7%), or C-reactive protein (77.3%).

“Additional research is required to determine best practices for laboratory measures that did not reach consensus,” the authors wrote. The study results “are intended to guide appropriate clinical decision-making,” they added. “Although our recommendations cannot replace clinical judgment based on the unique circumstances of individual patients, we believe they provide a framework for management of a typical, otherwise healthy patient being treated with isotretinoin for acne. More routine monitoring, or reduced monitoring, should be considered on a case-by-case basis accounting for the unique medical history, circumstances, and baseline abnormalities, if present, of each patient.”

“Practicing dermatologists, including myself, routinely check blood laboratory values during isotretinoin treatment,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “Even though just a small number of U.S.-based and international acne researchers were involved in this Delphi consensus statement, this article still makes us practicing clinicians feel more comfortable in checking fewer lab chemistries and also less frequently checking labs when we use isotretinoin.

“That said, I don’t think most of us are ready, because of legal reasons, to do that infrequent monitoring” during isotretinoin therapy, Dr. Green added. “I think most dermatologists do not routinely perform CBCs anymore, but we still feel obligated to check triglycerides and liver function more frequently” than recommended in the new study.

Dr. Mostaghimi reported receiving grants and personal fees from Pfizer, personal fees from Eli Lilly, personal fees and licensing from Concert, personal fees from Bioniz, holds equity and advisory board membership from Hims & Hers and Figure 1, personal fees from Digital Diagnostics, and personal fees from AbbVie outside the submitted work. Other authors reported serving as an adviser, a speaker consultant, investigator, and/or board member, or having received honoraria from different pharmaceutical companies; several authors had no disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

For generally healthy patients taking isotretinoin for acne and who have no underlying abnormalities or preexisting conditions that warrant further examination, it is sufficient to test ALT and triglycerides once at baseline, ideally within a month prior to the start of treatment, and a second time at peak dose.

Other tests such as complete blood cell counts and basic metabolic panels as well as specific laboratory tests such as LDL and HDL cholesterol should not be routinely monitored.

Those are key conclusions from a Delphi consensus study that included 22 acne experts from five continents and was published in JAMA Dermatology.

“Our results apply findings from recent literature and are in accordance with recent studies that have recommended against excessive laboratory monitoring,” senior corresponding author Arash Mostaghimi, MD, MPA, MPH, and coauthors wrote. “For instance, several studies in both teenagers and adults have shown that routine complete blood cell count laboratory tests are unnecessary without suspicion of an underlying abnormality and that rare abnormalities, if present, either resolved or remained stable without clinical impact on treatment. Likewise, liver function tests and lipid panels ordered at baseline and after 2 months of therapy were deemed sufficient if the clinical context and results do not suggest potential abnormalities.”

The authors also noted that, while published acne management guidelines exist, such as the American Academy of Dermatology work group guidelines and the National Institute for Health and Care Excellence guideline, “the specific recommendations surrounding laboratory monitoring frequency are nonstandardized and often nonspecific.”

To establish a consensus for isotretinoin laboratory monitoring, Dr. Mostaghimi, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to administer four rounds of electronic surveys to 22 board-certified dermatologists between 2021 and 2022. The primary outcome measured was whether participants could reach consensus on key isotretinoin lab monitoring parameters. Responses that failed to reach a threshold of 70% indicated no consensus.

The surveyed dermatologists had been in practice for a mean of 23.7 years, 54.5% were female, 54.5% practiced in an academic setting, and 63.9% were based in North America. They reached consensus for checking ALT within a month prior to initiation (89.5%) and at peak dose (89.5%), but not checking monthly (76.2%) or after completing treatment (73.7%). They also reached consensus on checking triglycerides within a month prior to initiation (89.5%) and at peak dose (78.9%) but not to check monthly (84.2%) or after completing treatment (73.7%).

Meanwhile, consensus was achieved for not checking complete blood cell count or basic metabolic panel parameters at any point during isotretinoin treatment (all > 70%), as well as not checking gamma-glutamyl transferase (78.9%), bilirubin (81.0%), albumin (72.7%), total protein (72.7%), LDL cholesterol (73.7%), HDL cholesterol (73.7%), or C-reactive protein (77.3%).

“Additional research is required to determine best practices for laboratory measures that did not reach consensus,” the authors wrote. The study results “are intended to guide appropriate clinical decision-making,” they added. “Although our recommendations cannot replace clinical judgment based on the unique circumstances of individual patients, we believe they provide a framework for management of a typical, otherwise healthy patient being treated with isotretinoin for acne. More routine monitoring, or reduced monitoring, should be considered on a case-by-case basis accounting for the unique medical history, circumstances, and baseline abnormalities, if present, of each patient.”

“Practicing dermatologists, including myself, routinely check blood laboratory values during isotretinoin treatment,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “Even though just a small number of U.S.-based and international acne researchers were involved in this Delphi consensus statement, this article still makes us practicing clinicians feel more comfortable in checking fewer lab chemistries and also less frequently checking labs when we use isotretinoin.

“That said, I don’t think most of us are ready, because of legal reasons, to do that infrequent monitoring” during isotretinoin therapy, Dr. Green added. “I think most dermatologists do not routinely perform CBCs anymore, but we still feel obligated to check triglycerides and liver function more frequently” than recommended in the new study.

Dr. Mostaghimi reported receiving grants and personal fees from Pfizer, personal fees from Eli Lilly, personal fees and licensing from Concert, personal fees from Bioniz, holds equity and advisory board membership from Hims & Hers and Figure 1, personal fees from Digital Diagnostics, and personal fees from AbbVie outside the submitted work. Other authors reported serving as an adviser, a speaker consultant, investigator, and/or board member, or having received honoraria from different pharmaceutical companies; several authors had no disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.