Federal Practitioner

Delta-9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, remains detectable in breast milk even after weeks of abstinence, new data show. The estimated half-life of THC in breast milk is 17 days, according to the study results, with a projected time to elimination of more than 6 weeks. The clinical importance of the remaining THC is up for debate, according to some experts.

“To limit THC effects on fetal brain development and promote safe breastfeeding, it is critical to emphasize marijuana abstention both early in pregnancy and post partum,” Erica M. Wymore, MD, MPH, an assistant professor of pediatrics and neonatology at the University of Colorado at Denver, Aurora, and colleagues wrote. The group published their results online March 8, 2021, in JAMA Pediatrics.

And while the study was a pharmacokinetic analysis rather than a safety investigation, Dr. Wymore said in an interview that the detectable levels of THC suggest any use is of concern and no safety thresholds have been established. “We wish we had more data on the potential effects on the neurocognitive development of children, but for now we must discourage any use in prepregnancy, pregnancy, and breastfeeding, as our national guidelines recommend.”

Therefore, the findings support current guidelines discouraging any cannabis use in mothers-to-be and breast-feeding mothers issued by national organizations, including those from the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the Academy of Breastfeeding Medicine.

Furthermore, the difficulties many mothers face in abstaining from marijuana, a commonly used drug in pregnancy, and the persistence of THC in maternal milk led the authors to question the feasibility of having women who use marijuana simply discard their breast milk until THC is cleared.

“We report challenges in abstention and prolonged excretion of THC in breast milk greater than 6 weeks among women with prenatal marijuana use,” they wrote. “These findings make the recommendations for mothers to discard breast milk until THC is undetectable unrealistic for mothers committed to breastfeeding.”

However, not all experts are equally concerned about low THC concentrations in breast milk. Neonatal pharmacologist Thomas R. Hale, PhD, a professor of pediatrics at Texas Tech University, Lubbock, said a previous study by his group showed that THC levels in maternal milk peaked within 60 minutes of a moderate dose of inhaled marijuana and fell to quite low levels over the next 4 hours. The highest concentration in maternal milk occurred shortly after the peak in plasma.

“So you can see that, just because a mom is drug screen positive, the clinical dose transferred to the infant is probably exceedingly low,” he said in an interview.

Dr. Hale also stressed that judgments about drugs in this context should weigh the risk of the drug against the risk of not breastfeeding. “All of us caution women not to use cannabis when pregnant or breastfeeding,” Dr. Hale said. “But when the decision has to be made as to whether a mom breastfeeds or not if she is drug screen positive, a lot of other factors must be analyzed to make such a decision.”
 

Study cohort

For the study, Dr. Wymore and colleagues screened 394 women who gave birth between Nov. 1, 2016, and June 30, 2019. Of those, 25 women, with a median age of 26 years, were eligible and enrolled. Inclusion criteria included known prenatal marijuana use, intention to breastfeed, and self-reported abstinence. Prenatal use primarily involved inhaling cannabis more than twice a week.

Of the 25 enrolled mothers, 12 who self-reported marijuana abstinence were in fact found to be abstinent according to the results of plasma analysis. Those who continued to use the substance were younger than the overall sample, with a median age of 21, and were less likely to have attended college (23%) than abstainers (58%).

The researchers prospectively collected data on self-reported marijuana usage and paired maternal plasma and breast milk samples several times a week. All participants had detectable THC in breast milk throughout the study. Initial median THC concentrations were 3.2 ng/mL (interquartile range, 1.2-6.8) within the first week after delivery. These increased to 5.5 ng/mL (IQR, 4.4-16.0) at 2 weeks and declined to 1.9 ng/mL (IQR, 1.1-4.3) at 6 weeks. In terms of ratio, the milk:plasma partition coefficient for THC was approximately 6:1 (IQR, 3.8:1-8.1:1).

Dr. Hale noted that, although THC was detectable in milk, the levels were exceedingly low. “This is where the risk assessment comes in. There’s a lot of hysteria in the cannabis field right now, and we’re going to need time and a lot more studies to really be able to predict any untoward complications.”

Dr. Wymore, however, countered that THC levels were low only in those who abstained and that her concerns relate not just to postpartum breast milk levels but the health effects on children of mothers’ cannabis use over the course of prepregnancy, pregnancy, and lactation. “[Dr. Hale’s] message makes it difficult for clinicians to counsel mothers since it goes against national guidelines,” she said. “We need to be consistent.”

But Dr. Wymore and other experts acknowledge the dilemma faced in that breast milk clearly offers substantial benefits for infant and child health. “The risks of an infant’s exposure to marijuana versus the benefit of breast milk must be considered,” said Amy B. Hair, MD, assistant professor of pediatrics and neonatal medicine at Baylor College of Medicine, Houston, who was not involved in the Colorado study. “And it’s unrealistic, as the study suggests, for mothers to discard breast milk for 6 weeks.”

Nevertheless, calling the findings of THC persistence after abstinence “troublesome,” Dr. Hair said the legalization of marijuana in some states gives the public the impression it’s safe to use marijuana even during pregnancy and lactation. “Research studies, however, are concerning for potential detrimental effects on brain growth and development in infants whose mothers use marijuana during pregnancy and breastfeeding,” she added.

Dr. Wymore stressed that more U.S. cannabis dispensaries must engage in rigorous point-of-sale counseling to women on the potential harms during pregnancy. This is the case in Canada, she noted, where recreational and medicinal cannabis has been legal since 2018 and more than 90% of outlets (vs. two thirds of their U.S. counterparts) advise women not to use cannabis during pregnancy or lactation, even for nausea.

“This is where many women are getting their information on cannabis,” she said. “We learned the hard way with alcohol and we don’t want to make the same mistake with marijuana.”

The study was funded by the Colorado Department of Public Health and Environment, the Children’s Hospital Colorado Research Institute, the Colorado Fetal Care Center, the Colorado Perinatal Clinical and Translational Research Center, and the Children’s Colorado Research Institute. Two study coauthors disclosed relationships with the private sector outside the submitted work. Dr. Hale and Dr. Hair have disclosed no competing interests with regard to their comments.

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

Delta-9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, remains detectable in breast milk even after weeks of abstinence, new data show. The estimated half-life of THC in breast milk is 17 days, according to the study results, with a projected time to elimination of more than 6 weeks. The clinical importance of the remaining THC is up for debate, according to some experts.

“To limit THC effects on fetal brain development and promote safe breastfeeding, it is critical to emphasize marijuana abstention both early in pregnancy and post partum,” Erica M. Wymore, MD, MPH, an assistant professor of pediatrics and neonatology at the University of Colorado at Denver, Aurora, and colleagues wrote. The group published their results online March 8, 2021, in JAMA Pediatrics.

And while the study was a pharmacokinetic analysis rather than a safety investigation, Dr. Wymore said in an interview that the detectable levels of THC suggest any use is of concern and no safety thresholds have been established. “We wish we had more data on the potential effects on the neurocognitive development of children, but for now we must discourage any use in prepregnancy, pregnancy, and breastfeeding, as our national guidelines recommend.”

Therefore, the findings support current guidelines discouraging any cannabis use in mothers-to-be and breast-feeding mothers issued by national organizations, including those from the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the Academy of Breastfeeding Medicine.

Furthermore, the difficulties many mothers face in abstaining from marijuana, a commonly used drug in pregnancy, and the persistence of THC in maternal milk led the authors to question the feasibility of having women who use marijuana simply discard their breast milk until THC is cleared.

“We report challenges in abstention and prolonged excretion of THC in breast milk greater than 6 weeks among women with prenatal marijuana use,” they wrote. “These findings make the recommendations for mothers to discard breast milk until THC is undetectable unrealistic for mothers committed to breastfeeding.”

However, not all experts are equally concerned about low THC concentrations in breast milk. Neonatal pharmacologist Thomas R. Hale, PhD, a professor of pediatrics at Texas Tech University, Lubbock, said a previous study by his group showed that THC levels in maternal milk peaked within 60 minutes of a moderate dose of inhaled marijuana and fell to quite low levels over the next 4 hours. The highest concentration in maternal milk occurred shortly after the peak in plasma.

“So you can see that, just because a mom is drug screen positive, the clinical dose transferred to the infant is probably exceedingly low,” he said in an interview.

Dr. Hale also stressed that judgments about drugs in this context should weigh the risk of the drug against the risk of not breastfeeding. “All of us caution women not to use cannabis when pregnant or breastfeeding,” Dr. Hale said. “But when the decision has to be made as to whether a mom breastfeeds or not if she is drug screen positive, a lot of other factors must be analyzed to make such a decision.”
 

Study cohort

For the study, Dr. Wymore and colleagues screened 394 women who gave birth between Nov. 1, 2016, and June 30, 2019. Of those, 25 women, with a median age of 26 years, were eligible and enrolled. Inclusion criteria included known prenatal marijuana use, intention to breastfeed, and self-reported abstinence. Prenatal use primarily involved inhaling cannabis more than twice a week.

Of the 25 enrolled mothers, 12 who self-reported marijuana abstinence were in fact found to be abstinent according to the results of plasma analysis. Those who continued to use the substance were younger than the overall sample, with a median age of 21, and were less likely to have attended college (23%) than abstainers (58%).

The researchers prospectively collected data on self-reported marijuana usage and paired maternal plasma and breast milk samples several times a week. All participants had detectable THC in breast milk throughout the study. Initial median THC concentrations were 3.2 ng/mL (interquartile range, 1.2-6.8) within the first week after delivery. These increased to 5.5 ng/mL (IQR, 4.4-16.0) at 2 weeks and declined to 1.9 ng/mL (IQR, 1.1-4.3) at 6 weeks. In terms of ratio, the milk:plasma partition coefficient for THC was approximately 6:1 (IQR, 3.8:1-8.1:1).

Dr. Hale noted that, although THC was detectable in milk, the levels were exceedingly low. “This is where the risk assessment comes in. There’s a lot of hysteria in the cannabis field right now, and we’re going to need time and a lot more studies to really be able to predict any untoward complications.”

Dr. Wymore, however, countered that THC levels were low only in those who abstained and that her concerns relate not just to postpartum breast milk levels but the health effects on children of mothers’ cannabis use over the course of prepregnancy, pregnancy, and lactation. “[Dr. Hale’s] message makes it difficult for clinicians to counsel mothers since it goes against national guidelines,” she said. “We need to be consistent.”

But Dr. Wymore and other experts acknowledge the dilemma faced in that breast milk clearly offers substantial benefits for infant and child health. “The risks of an infant’s exposure to marijuana versus the benefit of breast milk must be considered,” said Amy B. Hair, MD, assistant professor of pediatrics and neonatal medicine at Baylor College of Medicine, Houston, who was not involved in the Colorado study. “And it’s unrealistic, as the study suggests, for mothers to discard breast milk for 6 weeks.”

Nevertheless, calling the findings of THC persistence after abstinence “troublesome,” Dr. Hair said the legalization of marijuana in some states gives the public the impression it’s safe to use marijuana even during pregnancy and lactation. “Research studies, however, are concerning for potential detrimental effects on brain growth and development in infants whose mothers use marijuana during pregnancy and breastfeeding,” she added.

Dr. Wymore stressed that more U.S. cannabis dispensaries must engage in rigorous point-of-sale counseling to women on the potential harms during pregnancy. This is the case in Canada, she noted, where recreational and medicinal cannabis has been legal since 2018 and more than 90% of outlets (vs. two thirds of their U.S. counterparts) advise women not to use cannabis during pregnancy or lactation, even for nausea.

“This is where many women are getting their information on cannabis,” she said. “We learned the hard way with alcohol and we don’t want to make the same mistake with marijuana.”

The study was funded by the Colorado Department of Public Health and Environment, the Children’s Hospital Colorado Research Institute, the Colorado Fetal Care Center, the Colorado Perinatal Clinical and Translational Research Center, and the Children’s Colorado Research Institute. Two study coauthors disclosed relationships with the private sector outside the submitted work. Dr. Hale and Dr. Hair have disclosed no competing interests with regard to their comments.

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

Delta-9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, remains detectable in breast milk even after weeks of abstinence, new data show. The estimated half-life of THC in breast milk is 17 days, according to the study results, with a projected time to elimination of more than 6 weeks. The clinical importance of the remaining THC is up for debate, according to some experts.

“To limit THC effects on fetal brain development and promote safe breastfeeding, it is critical to emphasize marijuana abstention both early in pregnancy and post partum,” Erica M. Wymore, MD, MPH, an assistant professor of pediatrics and neonatology at the University of Colorado at Denver, Aurora, and colleagues wrote. The group published their results online March 8, 2021, in JAMA Pediatrics.

And while the study was a pharmacokinetic analysis rather than a safety investigation, Dr. Wymore said in an interview that the detectable levels of THC suggest any use is of concern and no safety thresholds have been established. “We wish we had more data on the potential effects on the neurocognitive development of children, but for now we must discourage any use in prepregnancy, pregnancy, and breastfeeding, as our national guidelines recommend.”

Therefore, the findings support current guidelines discouraging any cannabis use in mothers-to-be and breast-feeding mothers issued by national organizations, including those from the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the Academy of Breastfeeding Medicine.

Furthermore, the difficulties many mothers face in abstaining from marijuana, a commonly used drug in pregnancy, and the persistence of THC in maternal milk led the authors to question the feasibility of having women who use marijuana simply discard their breast milk until THC is cleared.

“We report challenges in abstention and prolonged excretion of THC in breast milk greater than 6 weeks among women with prenatal marijuana use,” they wrote. “These findings make the recommendations for mothers to discard breast milk until THC is undetectable unrealistic for mothers committed to breastfeeding.”

However, not all experts are equally concerned about low THC concentrations in breast milk. Neonatal pharmacologist Thomas R. Hale, PhD, a professor of pediatrics at Texas Tech University, Lubbock, said a previous study by his group showed that THC levels in maternal milk peaked within 60 minutes of a moderate dose of inhaled marijuana and fell to quite low levels over the next 4 hours. The highest concentration in maternal milk occurred shortly after the peak in plasma.

“So you can see that, just because a mom is drug screen positive, the clinical dose transferred to the infant is probably exceedingly low,” he said in an interview.

Dr. Hale also stressed that judgments about drugs in this context should weigh the risk of the drug against the risk of not breastfeeding. “All of us caution women not to use cannabis when pregnant or breastfeeding,” Dr. Hale said. “But when the decision has to be made as to whether a mom breastfeeds or not if she is drug screen positive, a lot of other factors must be analyzed to make such a decision.”
 

Study cohort

For the study, Dr. Wymore and colleagues screened 394 women who gave birth between Nov. 1, 2016, and June 30, 2019. Of those, 25 women, with a median age of 26 years, were eligible and enrolled. Inclusion criteria included known prenatal marijuana use, intention to breastfeed, and self-reported abstinence. Prenatal use primarily involved inhaling cannabis more than twice a week.

Of the 25 enrolled mothers, 12 who self-reported marijuana abstinence were in fact found to be abstinent according to the results of plasma analysis. Those who continued to use the substance were younger than the overall sample, with a median age of 21, and were less likely to have attended college (23%) than abstainers (58%).

The researchers prospectively collected data on self-reported marijuana usage and paired maternal plasma and breast milk samples several times a week. All participants had detectable THC in breast milk throughout the study. Initial median THC concentrations were 3.2 ng/mL (interquartile range, 1.2-6.8) within the first week after delivery. These increased to 5.5 ng/mL (IQR, 4.4-16.0) at 2 weeks and declined to 1.9 ng/mL (IQR, 1.1-4.3) at 6 weeks. In terms of ratio, the milk:plasma partition coefficient for THC was approximately 6:1 (IQR, 3.8:1-8.1:1).

Dr. Hale noted that, although THC was detectable in milk, the levels were exceedingly low. “This is where the risk assessment comes in. There’s a lot of hysteria in the cannabis field right now, and we’re going to need time and a lot more studies to really be able to predict any untoward complications.”

Dr. Wymore, however, countered that THC levels were low only in those who abstained and that her concerns relate not just to postpartum breast milk levels but the health effects on children of mothers’ cannabis use over the course of prepregnancy, pregnancy, and lactation. “[Dr. Hale’s] message makes it difficult for clinicians to counsel mothers since it goes against national guidelines,” she said. “We need to be consistent.”

But Dr. Wymore and other experts acknowledge the dilemma faced in that breast milk clearly offers substantial benefits for infant and child health. “The risks of an infant’s exposure to marijuana versus the benefit of breast milk must be considered,” said Amy B. Hair, MD, assistant professor of pediatrics and neonatal medicine at Baylor College of Medicine, Houston, who was not involved in the Colorado study. “And it’s unrealistic, as the study suggests, for mothers to discard breast milk for 6 weeks.”

Nevertheless, calling the findings of THC persistence after abstinence “troublesome,” Dr. Hair said the legalization of marijuana in some states gives the public the impression it’s safe to use marijuana even during pregnancy and lactation. “Research studies, however, are concerning for potential detrimental effects on brain growth and development in infants whose mothers use marijuana during pregnancy and breastfeeding,” she added.

Dr. Wymore stressed that more U.S. cannabis dispensaries must engage in rigorous point-of-sale counseling to women on the potential harms during pregnancy. This is the case in Canada, she noted, where recreational and medicinal cannabis has been legal since 2018 and more than 90% of outlets (vs. two thirds of their U.S. counterparts) advise women not to use cannabis during pregnancy or lactation, even for nausea.

“This is where many women are getting their information on cannabis,” she said. “We learned the hard way with alcohol and we don’t want to make the same mistake with marijuana.”

The study was funded by the Colorado Department of Public Health and Environment, the Children’s Hospital Colorado Research Institute, the Colorado Fetal Care Center, the Colorado Perinatal Clinical and Translational Research Center, and the Children’s Colorado Research Institute. Two study coauthors disclosed relationships with the private sector outside the submitted work. Dr. Hale and Dr. Hair have disclosed no competing interests with regard to their comments.

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

One year of melatonin, given at 20 mg nightly, after complete resection of non–small cell lung cancer (NSCLC) did not improve disease-free survival (DFS) in a phase 3 trial.

There was a hint of benefit with melatonin among patients with stage III/IV NSCLC. These patients had a hazard reduction of 25% in 5-year DFS. However, the median DFS for patients with advanced disease was the same whether they received melatonin or placebo – 18 months.

In the overall study population, melatonin had no beneficial effects on quality of life, sleep, anxiety, depression, pain, or fatigue, and it did not reduce adverse events from chemotherapy or radiation.

These results were reported in EClinicalMedicine.

“In light of the results, we do not recommend the inclusion of adjuvant melatonin for patients with early-stage NSCLC. Evidence suggests there may be a benefit for those with late-stage disease,” the authors wrote. “However, because of the mixed findings observed, we recommend a follow-up randomized, controlled trial involving a larger population focusing on later-stage resected lung cancer to clarify these results.”

“I would very much like to pursue another controlled study of melatonin specifically in a group of late-stage lung cancer and possibly in other more advanced cancer types,” said lead author Dugald Seely, ND, of the Canadian College of Naturopathic Medicine in Toronto.
 

Study rationale and design

Melatonin has shown promise for treating patients with lung cancer, Dr. Seely and colleagues noted. Melatonin is often recommended by naturopathic doctors following lung cancer surgery, but until now there was no high-level evidence regarding the practice.

For their study, Dr. Seely and colleagues evaluated 709 patients who had undergone NSCLC resection. The patients were randomized to receive placebo (n = 353) or melatonin (n = 356) 1 hour before bedtime for 1 year. A 20-mg melatonin dose was used, which is common in clinical practice and research.

The study arms were well matched, with no “clinically meaningful” differences in demographics, surgery type, cancer type, stage of cancer, or preoperative comorbidities, according to the researchers.

The mean age in both treatment arms was 67 years. Overall, 134 participants received adjuvant chemotherapy (66 melatonin, 68 placebo), and 43 had adjuvant radiation (22 melatonin, 21 placebo).
 

Results

For 2-year DFS, melatonin showed an adjusted relative risk of 1.01 (95% confidence interval, 0.83-1.22; P = .94) versus placebo. The adjusted relative risk in the per-protocol analysis was 1.12 (95% CI, 0.96-1.32; P = .14.)

At 5 years, the median DFS was not reached in either treatment arm. Melatonin showed a hazard ratio of 0.97 (95% CI, 0.86-1.09; P = .84) for 5-year DFS.

Among patients with stage I-II NSCLC, the median DFS was not reached at 5 years in either treatment arm. Among patients with stage III-IV NSCLC, the median DFS was 18 months in both arms.

Melatonin showed a hazard ratio of 0.97 (95% CI, 0.85-1.11; P = .66) in patients with early-stage NSCLC and a hazard reduction of 25% (HR, 0.75; 95% CI, 0.61-0.92; P = .005) in patients with late-stage NSCLC.

For the entire cohort, there were no significant differences between treatment arms in the number, severity, or seriousness of adverse events. Likewise, there were no significant differences between the treatment arms with regard to fatigue, quality of life, or sleep at 1 or 2 years.

Dr. Seely said the most surprising thing about this study was that melatonin didn’t help with sleep.

“Since initiation of the trial, my thinking on the right dose of melatonin to support sleep has changed. Clinically, I see extended-release and, indeed, lower doses to be more effective than 20 mg nightly,” he noted.

Dr. Seely and colleagues also assessed proposed mechanisms for melatonin’s possible benefit in NSCLC but found no effect on natural killer cell cytotoxicity or phenotype and no effect on blood levels of inflammatory cytokines in a substudy of 92 patients.

This research was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation. The researchers had no relevant disclosures.

[email protected]

One year of melatonin, given at 20 mg nightly, after complete resection of non–small cell lung cancer (NSCLC) did not improve disease-free survival (DFS) in a phase 3 trial.

There was a hint of benefit with melatonin among patients with stage III/IV NSCLC. These patients had a hazard reduction of 25% in 5-year DFS. However, the median DFS for patients with advanced disease was the same whether they received melatonin or placebo – 18 months.

In the overall study population, melatonin had no beneficial effects on quality of life, sleep, anxiety, depression, pain, or fatigue, and it did not reduce adverse events from chemotherapy or radiation.

These results were reported in EClinicalMedicine.

“In light of the results, we do not recommend the inclusion of adjuvant melatonin for patients with early-stage NSCLC. Evidence suggests there may be a benefit for those with late-stage disease,” the authors wrote. “However, because of the mixed findings observed, we recommend a follow-up randomized, controlled trial involving a larger population focusing on later-stage resected lung cancer to clarify these results.”

“I would very much like to pursue another controlled study of melatonin specifically in a group of late-stage lung cancer and possibly in other more advanced cancer types,” said lead author Dugald Seely, ND, of the Canadian College of Naturopathic Medicine in Toronto.
 

Study rationale and design

Melatonin has shown promise for treating patients with lung cancer, Dr. Seely and colleagues noted. Melatonin is often recommended by naturopathic doctors following lung cancer surgery, but until now there was no high-level evidence regarding the practice.

For their study, Dr. Seely and colleagues evaluated 709 patients who had undergone NSCLC resection. The patients were randomized to receive placebo (n = 353) or melatonin (n = 356) 1 hour before bedtime for 1 year. A 20-mg melatonin dose was used, which is common in clinical practice and research.

The study arms were well matched, with no “clinically meaningful” differences in demographics, surgery type, cancer type, stage of cancer, or preoperative comorbidities, according to the researchers.

The mean age in both treatment arms was 67 years. Overall, 134 participants received adjuvant chemotherapy (66 melatonin, 68 placebo), and 43 had adjuvant radiation (22 melatonin, 21 placebo).
 

Results

For 2-year DFS, melatonin showed an adjusted relative risk of 1.01 (95% confidence interval, 0.83-1.22; P = .94) versus placebo. The adjusted relative risk in the per-protocol analysis was 1.12 (95% CI, 0.96-1.32; P = .14.)

At 5 years, the median DFS was not reached in either treatment arm. Melatonin showed a hazard ratio of 0.97 (95% CI, 0.86-1.09; P = .84) for 5-year DFS.

Among patients with stage I-II NSCLC, the median DFS was not reached at 5 years in either treatment arm. Among patients with stage III-IV NSCLC, the median DFS was 18 months in both arms.

Melatonin showed a hazard ratio of 0.97 (95% CI, 0.85-1.11; P = .66) in patients with early-stage NSCLC and a hazard reduction of 25% (HR, 0.75; 95% CI, 0.61-0.92; P = .005) in patients with late-stage NSCLC.

For the entire cohort, there were no significant differences between treatment arms in the number, severity, or seriousness of adverse events. Likewise, there were no significant differences between the treatment arms with regard to fatigue, quality of life, or sleep at 1 or 2 years.

Dr. Seely said the most surprising thing about this study was that melatonin didn’t help with sleep.

“Since initiation of the trial, my thinking on the right dose of melatonin to support sleep has changed. Clinically, I see extended-release and, indeed, lower doses to be more effective than 20 mg nightly,” he noted.

Dr. Seely and colleagues also assessed proposed mechanisms for melatonin’s possible benefit in NSCLC but found no effect on natural killer cell cytotoxicity or phenotype and no effect on blood levels of inflammatory cytokines in a substudy of 92 patients.

This research was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation. The researchers had no relevant disclosures.

[email protected]

One year of melatonin, given at 20 mg nightly, after complete resection of non–small cell lung cancer (NSCLC) did not improve disease-free survival (DFS) in a phase 3 trial.

There was a hint of benefit with melatonin among patients with stage III/IV NSCLC. These patients had a hazard reduction of 25% in 5-year DFS. However, the median DFS for patients with advanced disease was the same whether they received melatonin or placebo – 18 months.

In the overall study population, melatonin had no beneficial effects on quality of life, sleep, anxiety, depression, pain, or fatigue, and it did not reduce adverse events from chemotherapy or radiation.

These results were reported in EClinicalMedicine.

“In light of the results, we do not recommend the inclusion of adjuvant melatonin for patients with early-stage NSCLC. Evidence suggests there may be a benefit for those with late-stage disease,” the authors wrote. “However, because of the mixed findings observed, we recommend a follow-up randomized, controlled trial involving a larger population focusing on later-stage resected lung cancer to clarify these results.”

“I would very much like to pursue another controlled study of melatonin specifically in a group of late-stage lung cancer and possibly in other more advanced cancer types,” said lead author Dugald Seely, ND, of the Canadian College of Naturopathic Medicine in Toronto.
 

Study rationale and design

Melatonin has shown promise for treating patients with lung cancer, Dr. Seely and colleagues noted. Melatonin is often recommended by naturopathic doctors following lung cancer surgery, but until now there was no high-level evidence regarding the practice.

For their study, Dr. Seely and colleagues evaluated 709 patients who had undergone NSCLC resection. The patients were randomized to receive placebo (n = 353) or melatonin (n = 356) 1 hour before bedtime for 1 year. A 20-mg melatonin dose was used, which is common in clinical practice and research.

The study arms were well matched, with no “clinically meaningful” differences in demographics, surgery type, cancer type, stage of cancer, or preoperative comorbidities, according to the researchers.

The mean age in both treatment arms was 67 years. Overall, 134 participants received adjuvant chemotherapy (66 melatonin, 68 placebo), and 43 had adjuvant radiation (22 melatonin, 21 placebo).
 

Results

For 2-year DFS, melatonin showed an adjusted relative risk of 1.01 (95% confidence interval, 0.83-1.22; P = .94) versus placebo. The adjusted relative risk in the per-protocol analysis was 1.12 (95% CI, 0.96-1.32; P = .14.)

At 5 years, the median DFS was not reached in either treatment arm. Melatonin showed a hazard ratio of 0.97 (95% CI, 0.86-1.09; P = .84) for 5-year DFS.

Among patients with stage I-II NSCLC, the median DFS was not reached at 5 years in either treatment arm. Among patients with stage III-IV NSCLC, the median DFS was 18 months in both arms.

Melatonin showed a hazard ratio of 0.97 (95% CI, 0.85-1.11; P = .66) in patients with early-stage NSCLC and a hazard reduction of 25% (HR, 0.75; 95% CI, 0.61-0.92; P = .005) in patients with late-stage NSCLC.

For the entire cohort, there were no significant differences between treatment arms in the number, severity, or seriousness of adverse events. Likewise, there were no significant differences between the treatment arms with regard to fatigue, quality of life, or sleep at 1 or 2 years.

Dr. Seely said the most surprising thing about this study was that melatonin didn’t help with sleep.

“Since initiation of the trial, my thinking on the right dose of melatonin to support sleep has changed. Clinically, I see extended-release and, indeed, lower doses to be more effective than 20 mg nightly,” he noted.

Dr. Seely and colleagues also assessed proposed mechanisms for melatonin’s possible benefit in NSCLC but found no effect on natural killer cell cytotoxicity or phenotype and no effect on blood levels of inflammatory cytokines in a substudy of 92 patients.

This research was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation. The researchers had no relevant disclosures.

[email protected]

ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.

Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.

“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.

The study was published online March 10, 2021, in JAMA Psychiatry.
 

Antihypertensives and mental illness

Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.

Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.

In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).

The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.

The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
 

Could ACE inhibitors worsen symptoms or trigger episodes?

In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.

“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.

Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”

“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.

“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
 

Caution warranted

Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.

“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.

“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.

That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, we should be looking at people we’re treating with these drugs to see – might we be tipping some of them into illness states that they otherwise wouldn’t experience?”

Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.

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

ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.

Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.

“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.

The study was published online March 10, 2021, in JAMA Psychiatry.
 

Antihypertensives and mental illness

Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.

Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.

In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).

The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.

The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
 

Could ACE inhibitors worsen symptoms or trigger episodes?

In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.

“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.

Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”

“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.

“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
 

Caution warranted

Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.

“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.

“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.

That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, we should be looking at people we’re treating with these drugs to see – might we be tipping some of them into illness states that they otherwise wouldn’t experience?”

Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.

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

ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.

Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.

“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.

The study was published online March 10, 2021, in JAMA Psychiatry.
 

Antihypertensives and mental illness

Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.

Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.

In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).

The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.

The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
 

Could ACE inhibitors worsen symptoms or trigger episodes?

In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.

“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.

Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”

“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.

“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
 

Caution warranted

Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.

“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.

“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.

That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, we should be looking at people we’re treating with these drugs to see – might we be tipping some of them into illness states that they otherwise wouldn’t experience?”

Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.

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

Women with polycystic ovary syndrome (PCOS) face an almost 30% increased risk for COVID-19 compared with unaffected women, even after adjusting for cardiometabolic and other related factors, suggests an analysis of United Kingdom primary care data.

“Our research has highlighted that women with PCOS are an often overlooked and potentially high-risk population for contracting COVID-19,” said joint senior author Wiebke Arlt, MD, PhD, director of the Institute of Metabolism and Systems Research at the University of Birmingham (England), in a press release.

“Before the onset of the COVID-19 pandemic, women with PCOS consistently report fragmented care, delayed diagnosis and a perception of poor clinician understanding of their condition,” added co-author Michael W. O’Reilly, MD, PhD, University of Medicine and Health Sciences, Dublin.

“Women suffering from this condition may fear, with some degree of justification, that an enhanced risk of COVID-19 infection will further compromise timely access to health care and serve to increase the sense of disenfranchisement currently experienced by many patients,” he added.

Consequently, “these findings need to be considered when designing public health policy and advice as our understanding of COVID-19 evolves,” noted first author Anuradhaa Subramanian, PhD Student, Institute of Applied Health Research, University of Birmingham.

The research was published by the European Journal of Endocrinology on March 9.
 

Women with PCOS: A distinct subgroup?

PCOS, which is thought to affect up to 16% of women, is associated with a significantly increased risk for type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, all which have been linked to more severe COVID-19.

The condition is more prevalent in Black and South Asian women, who also appear to have an increased risk for severe COVID-19 vs. their White counterparts.

However, women and younger people in general have a lower overall risk for severe COVID-19 and mortality compared with older people and men.

Women with PCOS may therefore “represent a distinct subgroup of women at higher than average [on the basis of their sex and age] risk of adverse COVID-19–related outcomes,” the researchers note.

To investigate further, they collated data from The Health Improvement Network primary care database, which includes information from 365 active general practices in the U.K. for the period Jan. 31, 2020, to July 22, 2020.

They identified women with PCOS or a coded diagnosis of polycystic ovaries (PCO), and then for each woman randomly selected four unaffected controls matched for age and general practice location.

They included 21,292 women with PCOS/PCO and 78,310 controls, who had a mean age at study entry of 39.3 years and 39.5 years, respectively. The mean age at diagnosis of PCOS was 27 years, and the mean duration of the condition was 12.4 years.

The crude incidence of COVID-19 was 18.1 per 1000 person-years among women with PCOS vs. 11.9 per 1000 person-years in those without.

Cox regression analysis adjusted for age indicated that women with PCOS faced a significantly increased risk for COVID-19 than those without, at a hazard ratio of 1.51 (P < .001).

Further adjustment for body mass index (BMI) and age reduced the hazard ratio to 1.36 (P = .001).

In the fully adjusted model, which also took into account impaired glucose regulation, androgen excess, anovulation, hypertension, and other PCOS-related factors, the hazard ratio remained significant, at 1.28 (P = .015).
 

For shielding, balance benefits with impact on mental health

Joint senior author Krishnarajah Nirantharakumar, MD, PhD, also of the University of Birmingham, commented that, despite the increased risks, shielding strategies for COVID-19 need to take into account the impact of PCOS on women’s mental health.

“The risk of mental health problems, including low self-esteem, anxiety, and depression, is significantly higher in women with PCOS,” he said, “and advice on strict adherence to social distancing needs to be tempered by the associated risk of exacerbating these underlying problems.”

Arlt also pointed out that the study only looked at the incidence of COVID-19 infection, rather than outcomes.

“Our study does not provide information on the risk of a severe course of the COVID-19 infection or on the risk of COVID-19–related long-term complications [in women with PCOS], and further research is required,” she concluded.

The study was funded by Health Data Research UK and supported by the Wellcome Trust, the Health Research Board, and the National Institute for Health Research Birmingham Biomedical Research Centre based at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. The study authors have disclosed no relevant financial relationships.

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

Women with polycystic ovary syndrome (PCOS) face an almost 30% increased risk for COVID-19 compared with unaffected women, even after adjusting for cardiometabolic and other related factors, suggests an analysis of United Kingdom primary care data.

“Our research has highlighted that women with PCOS are an often overlooked and potentially high-risk population for contracting COVID-19,” said joint senior author Wiebke Arlt, MD, PhD, director of the Institute of Metabolism and Systems Research at the University of Birmingham (England), in a press release.

“Before the onset of the COVID-19 pandemic, women with PCOS consistently report fragmented care, delayed diagnosis and a perception of poor clinician understanding of their condition,” added co-author Michael W. O’Reilly, MD, PhD, University of Medicine and Health Sciences, Dublin.

“Women suffering from this condition may fear, with some degree of justification, that an enhanced risk of COVID-19 infection will further compromise timely access to health care and serve to increase the sense of disenfranchisement currently experienced by many patients,” he added.

Consequently, “these findings need to be considered when designing public health policy and advice as our understanding of COVID-19 evolves,” noted first author Anuradhaa Subramanian, PhD Student, Institute of Applied Health Research, University of Birmingham.

The research was published by the European Journal of Endocrinology on March 9.
 

Women with PCOS: A distinct subgroup?

PCOS, which is thought to affect up to 16% of women, is associated with a significantly increased risk for type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, all which have been linked to more severe COVID-19.

The condition is more prevalent in Black and South Asian women, who also appear to have an increased risk for severe COVID-19 vs. their White counterparts.

However, women and younger people in general have a lower overall risk for severe COVID-19 and mortality compared with older people and men.

Women with PCOS may therefore “represent a distinct subgroup of women at higher than average [on the basis of their sex and age] risk of adverse COVID-19–related outcomes,” the researchers note.

To investigate further, they collated data from The Health Improvement Network primary care database, which includes information from 365 active general practices in the U.K. for the period Jan. 31, 2020, to July 22, 2020.

They identified women with PCOS or a coded diagnosis of polycystic ovaries (PCO), and then for each woman randomly selected four unaffected controls matched for age and general practice location.

They included 21,292 women with PCOS/PCO and 78,310 controls, who had a mean age at study entry of 39.3 years and 39.5 years, respectively. The mean age at diagnosis of PCOS was 27 years, and the mean duration of the condition was 12.4 years.

The crude incidence of COVID-19 was 18.1 per 1000 person-years among women with PCOS vs. 11.9 per 1000 person-years in those without.

Cox regression analysis adjusted for age indicated that women with PCOS faced a significantly increased risk for COVID-19 than those without, at a hazard ratio of 1.51 (P < .001).

Further adjustment for body mass index (BMI) and age reduced the hazard ratio to 1.36 (P = .001).

In the fully adjusted model, which also took into account impaired glucose regulation, androgen excess, anovulation, hypertension, and other PCOS-related factors, the hazard ratio remained significant, at 1.28 (P = .015).
 

For shielding, balance benefits with impact on mental health

Joint senior author Krishnarajah Nirantharakumar, MD, PhD, also of the University of Birmingham, commented that, despite the increased risks, shielding strategies for COVID-19 need to take into account the impact of PCOS on women’s mental health.

“The risk of mental health problems, including low self-esteem, anxiety, and depression, is significantly higher in women with PCOS,” he said, “and advice on strict adherence to social distancing needs to be tempered by the associated risk of exacerbating these underlying problems.”

Arlt also pointed out that the study only looked at the incidence of COVID-19 infection, rather than outcomes.

“Our study does not provide information on the risk of a severe course of the COVID-19 infection or on the risk of COVID-19–related long-term complications [in women with PCOS], and further research is required,” she concluded.

The study was funded by Health Data Research UK and supported by the Wellcome Trust, the Health Research Board, and the National Institute for Health Research Birmingham Biomedical Research Centre based at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. The study authors have disclosed no relevant financial relationships.

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

Women with polycystic ovary syndrome (PCOS) face an almost 30% increased risk for COVID-19 compared with unaffected women, even after adjusting for cardiometabolic and other related factors, suggests an analysis of United Kingdom primary care data.

“Our research has highlighted that women with PCOS are an often overlooked and potentially high-risk population for contracting COVID-19,” said joint senior author Wiebke Arlt, MD, PhD, director of the Institute of Metabolism and Systems Research at the University of Birmingham (England), in a press release.

“Before the onset of the COVID-19 pandemic, women with PCOS consistently report fragmented care, delayed diagnosis and a perception of poor clinician understanding of their condition,” added co-author Michael W. O’Reilly, MD, PhD, University of Medicine and Health Sciences, Dublin.

“Women suffering from this condition may fear, with some degree of justification, that an enhanced risk of COVID-19 infection will further compromise timely access to health care and serve to increase the sense of disenfranchisement currently experienced by many patients,” he added.

Consequently, “these findings need to be considered when designing public health policy and advice as our understanding of COVID-19 evolves,” noted first author Anuradhaa Subramanian, PhD Student, Institute of Applied Health Research, University of Birmingham.

The research was published by the European Journal of Endocrinology on March 9.
 

Women with PCOS: A distinct subgroup?

PCOS, which is thought to affect up to 16% of women, is associated with a significantly increased risk for type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, all which have been linked to more severe COVID-19.

The condition is more prevalent in Black and South Asian women, who also appear to have an increased risk for severe COVID-19 vs. their White counterparts.

However, women and younger people in general have a lower overall risk for severe COVID-19 and mortality compared with older people and men.

Women with PCOS may therefore “represent a distinct subgroup of women at higher than average [on the basis of their sex and age] risk of adverse COVID-19–related outcomes,” the researchers note.

To investigate further, they collated data from The Health Improvement Network primary care database, which includes information from 365 active general practices in the U.K. for the period Jan. 31, 2020, to July 22, 2020.

They identified women with PCOS or a coded diagnosis of polycystic ovaries (PCO), and then for each woman randomly selected four unaffected controls matched for age and general practice location.

They included 21,292 women with PCOS/PCO and 78,310 controls, who had a mean age at study entry of 39.3 years and 39.5 years, respectively. The mean age at diagnosis of PCOS was 27 years, and the mean duration of the condition was 12.4 years.

The crude incidence of COVID-19 was 18.1 per 1000 person-years among women with PCOS vs. 11.9 per 1000 person-years in those without.

Cox regression analysis adjusted for age indicated that women with PCOS faced a significantly increased risk for COVID-19 than those without, at a hazard ratio of 1.51 (P < .001).

Further adjustment for body mass index (BMI) and age reduced the hazard ratio to 1.36 (P = .001).

In the fully adjusted model, which also took into account impaired glucose regulation, androgen excess, anovulation, hypertension, and other PCOS-related factors, the hazard ratio remained significant, at 1.28 (P = .015).
 

For shielding, balance benefits with impact on mental health

Joint senior author Krishnarajah Nirantharakumar, MD, PhD, also of the University of Birmingham, commented that, despite the increased risks, shielding strategies for COVID-19 need to take into account the impact of PCOS on women’s mental health.

“The risk of mental health problems, including low self-esteem, anxiety, and depression, is significantly higher in women with PCOS,” he said, “and advice on strict adherence to social distancing needs to be tempered by the associated risk of exacerbating these underlying problems.”

Arlt also pointed out that the study only looked at the incidence of COVID-19 infection, rather than outcomes.

“Our study does not provide information on the risk of a severe course of the COVID-19 infection or on the risk of COVID-19–related long-term complications [in women with PCOS], and further research is required,” she concluded.

The study was funded by Health Data Research UK and supported by the Wellcome Trust, the Health Research Board, and the National Institute for Health Research Birmingham Biomedical Research Centre based at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. The study authors have disclosed no relevant financial relationships.

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

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

Family physician Mitchell A. Kaminski, MD, MBA, was still awash in feelings of joy and relief at recently being vaccinated against COVID-19 when a patient’s comments stopped him cold. The patient, a middle-aged man with several comorbidities had just declined the pneumonia vaccine – and he added, without prompting, that he wouldn’t be getting the COVID vaccine either. This patient had heard getting vaccinated could kill him.

Dr. Kaminski countered with medical facts, including that the very rare side effects hadn’t killed anyone in the United States but COVID was killing thousands of people every day. “Well then, I’ll just risk getting COVID,” Dr. Kaminski recalled the patient saying. Conversation over.

That experience caused Dr. Kaminski, who is program director for population health at Thomas Jefferson University, Philadelphia, to rethink the way he talks to patients who are uncertain or skeptical about getting a COVID-19 vaccine. Now, if he saw that patient who seemed fearful of dying from a vaccination, Dr. Kaminski said he would be more curious.

Instead of outright contradicting the beliefs of a patient who is reluctant to get vaccinated, Dr. Kaminski now gently asks about the reasons for their discomfort and offers information about the vaccines. But mostly, he listens.

©Sean Warren/iStockphoto.com

Conversations between physicians and patients about the risks that come with getting a COVID-19 vaccine are becoming more common in general as eligibility for immunizations expands. Physicians are using a variety of methods to communicate about the safety and importance of getting vaccinated that they think will lead to more of their patients getting a COVID-19 vaccine.

About 80% of Americans say that they are most likely to turn to doctors, nurses and other health professionals for help in deciding whether to get the COVID vaccine, according to research by the Kaiser Family Foundation.
 

Getting beyond the distrust

While patients often feel a strong connection with their health providers, distrust in the medical establishment still exists, especially among some populations. The Kaiser Family Foundation reported that a third of Black respondents are taking a “wait-and-see” approach, while 23% said they will get it only if it’s required – or not at all.

Distrust persists from historical racist events in medicine, such as the infamous Tuskegee experiments in which treatment was withheld from Black men with syphilis. But physicians shouldn’t assume that all Black patients have the same reasons for vaccine hesitancy, said Krys Foster, MD, MPH, a family physician at Thomas Jefferson University.

“In my experience caring for patients who are uncertain or have concerns about receiving the vaccine, I’ve learned that many are just seeking more information, or even my approval to say that it is safe to proceed given their medical history,” she said.

Sources such as the COVID Racial Data Tracker have found that Black Americans have a higher COVID death rate than other racial or ethnic groups, making vaccination even more vital. Yet fear of the vaccine could be triggered by misinformation that can be found in various places online, Dr. Foster said.

To encourage people to get vaccinated and dispel false information, Dr. Foster takes time to discuss how safe it is to get a COVID-19 vaccine and the vaccines’ side effects, then quickly pivots to discussing how to get vaccinated.

It can be difficult for some people to find appointments or access testing sites. The failure to get the vaccine shouldn’t automatically be attributed to “hesitancy,” she said. “The onus is on the medical community to help fix the health injustices inflicted on communities of color by providing equitable information and access and stop placing blame on them for having the ‘wrong’ vaccine attitude.”
 

Give your testimonial

Jamie Loehr, MD, of Cayuga Family Medicine in Ithaca, N.Y., said he has always had a higher-than-average number of patients who refused or delayed their children’s vaccines. He does not kick them out of his practice but politely continues to educate them about the vaccines.

When patients ask Dr. Loehr if he trusts the vaccine, he responds with confidence: “I not only believe in it, I got it and I recommend it to anyone who can possibly get it.”

He was surprised recently when a mother who has expressed reluctance to vaccinate her young children came for a checkup and told him she had already received a COVID vaccine. “She made the decision on her own that this was important enough that she wanted to get it,” he said.
 

Health care worker hesitancy

Some health care workers’ unease about being at the front of the line for vaccines may be another source of vaccine hesitancy among members of the general population that physicians need to address. In a survey of almost 3,500 health care workers conducted in October and November 2020 and published in January 2021 in Vaccines, only about a third (36%) said they would get the vaccine as soon as it became available. By mid- to late-February, 54% of health care workers reported having been vaccinated and another 10% planned to get the vaccine as soon as possible, according to the Kaiser Family Foundation COVID-19 Vaccine Monitor.

Resolving doubts about the vaccines requires a thoughtful approach toward health care colleagues, said Eileen Barrett, MD, MPH, an internist and hospitalist who was a coauthor of the Vaccines paper and who serves on the editorial advisory board of Internal Medicine News. “We should meet people where they are and do our best to hear their concerns, listening thoughtfully without condescension. Validate how important their role is in endorsing vaccination and also validate asking questions.”

There’s power in the strong personal testimonial of physicians and other health care workers – not just to influence patients, but as a model for fellow health professionals, as well, noted Dr. Barrett, who cares for COVID-19 patients and is associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.
 

‘Do it for your loved ones’

The Reagan-Udall Foundation, a nonprofit organization created by Congress to support the Food and Drug Administration, tested some messaging with focus groups. Participants responded favorably to this statement about why the vaccines were developed so quickly: “Vaccine development moved faster than normal because everyone’s making it their highest priority.”

People did not feel motivated to get the vaccine out of a sense of civic duty, said Susan Winckler, RPh, Esq, who is CEO of the foundation. But they did think the following was a good reason to get vaccinated: “By getting a vaccine, I could protect my children, my parents, and other loved ones.”

Physicians also can work with community influencers, such as faith leaders, to build confidence in vaccines. That’s part of the strategy of Roll Up Your Sleeves, a campaign spearheaded by agilon health, a company that partners with physician practices to develop value-based care for Medicare Advantage patients.

For example, Wilmington Health in North Carolina answered questions about the vaccines in Facebook Live events and created a Spanish-language video to boost vaccine confidence in the Latinx community. Additionally, PriMED Physicians in Dayton, Ohio, reached out to Black churches to provide a vaccine-awareness video and a PriMED doctor participated in a webinar sponsored by the Nigerian Women Cultural Organization to help dispel myths about COVID-19 and the vaccines.

“This is a way to deepen our relationship with our patients,” said Ben Kornitzer, MD, chief medical officer of agilon. “It’s helping to walk them through this door where on one side is the pandemic and social isolation and on the other side is a return to their life and loved ones.”

The messages provided by primary care physicians can be powerful and affirming, said Ms. Winckler.

“The path forward is to make a space for people to ask questions,” she continued, noting that the Reagan-Udall Foundation provides charts that show how the timeline for vaccine development was compressed without skipping any steps.

Strategies and background information on how to reinforce confidence in COVID-19 vaccines are also available on a page of the Centers for Disease Control and Prevention’s website.

None of the experts interviewed reported any relevant conflicts of interest. The Reagan-Udall Foundation has received sponsorships from Johnson & Johnson and AstraZeneca and has had a safety surveillance contract with Pfizer.

Family physician Mitchell A. Kaminski, MD, MBA, was still awash in feelings of joy and relief at recently being vaccinated against COVID-19 when a patient’s comments stopped him cold. The patient, a middle-aged man with several comorbidities had just declined the pneumonia vaccine – and he added, without prompting, that he wouldn’t be getting the COVID vaccine either. This patient had heard getting vaccinated could kill him.

Dr. Kaminski countered with medical facts, including that the very rare side effects hadn’t killed anyone in the United States but COVID was killing thousands of people every day. “Well then, I’ll just risk getting COVID,” Dr. Kaminski recalled the patient saying. Conversation over.

That experience caused Dr. Kaminski, who is program director for population health at Thomas Jefferson University, Philadelphia, to rethink the way he talks to patients who are uncertain or skeptical about getting a COVID-19 vaccine. Now, if he saw that patient who seemed fearful of dying from a vaccination, Dr. Kaminski said he would be more curious.

Instead of outright contradicting the beliefs of a patient who is reluctant to get vaccinated, Dr. Kaminski now gently asks about the reasons for their discomfort and offers information about the vaccines. But mostly, he listens.

©Sean Warren/iStockphoto.com

Conversations between physicians and patients about the risks that come with getting a COVID-19 vaccine are becoming more common in general as eligibility for immunizations expands. Physicians are using a variety of methods to communicate about the safety and importance of getting vaccinated that they think will lead to more of their patients getting a COVID-19 vaccine.

About 80% of Americans say that they are most likely to turn to doctors, nurses and other health professionals for help in deciding whether to get the COVID vaccine, according to research by the Kaiser Family Foundation.
 

Getting beyond the distrust

While patients often feel a strong connection with their health providers, distrust in the medical establishment still exists, especially among some populations. The Kaiser Family Foundation reported that a third of Black respondents are taking a “wait-and-see” approach, while 23% said they will get it only if it’s required – or not at all.

Distrust persists from historical racist events in medicine, such as the infamous Tuskegee experiments in which treatment was withheld from Black men with syphilis. But physicians shouldn’t assume that all Black patients have the same reasons for vaccine hesitancy, said Krys Foster, MD, MPH, a family physician at Thomas Jefferson University.

“In my experience caring for patients who are uncertain or have concerns about receiving the vaccine, I’ve learned that many are just seeking more information, or even my approval to say that it is safe to proceed given their medical history,” she said.

Sources such as the COVID Racial Data Tracker have found that Black Americans have a higher COVID death rate than other racial or ethnic groups, making vaccination even more vital. Yet fear of the vaccine could be triggered by misinformation that can be found in various places online, Dr. Foster said.

To encourage people to get vaccinated and dispel false information, Dr. Foster takes time to discuss how safe it is to get a COVID-19 vaccine and the vaccines’ side effects, then quickly pivots to discussing how to get vaccinated.

It can be difficult for some people to find appointments or access testing sites. The failure to get the vaccine shouldn’t automatically be attributed to “hesitancy,” she said. “The onus is on the medical community to help fix the health injustices inflicted on communities of color by providing equitable information and access and stop placing blame on them for having the ‘wrong’ vaccine attitude.”
 

Give your testimonial

Jamie Loehr, MD, of Cayuga Family Medicine in Ithaca, N.Y., said he has always had a higher-than-average number of patients who refused or delayed their children’s vaccines. He does not kick them out of his practice but politely continues to educate them about the vaccines.

When patients ask Dr. Loehr if he trusts the vaccine, he responds with confidence: “I not only believe in it, I got it and I recommend it to anyone who can possibly get it.”

He was surprised recently when a mother who has expressed reluctance to vaccinate her young children came for a checkup and told him she had already received a COVID vaccine. “She made the decision on her own that this was important enough that she wanted to get it,” he said.
 

Health care worker hesitancy

Some health care workers’ unease about being at the front of the line for vaccines may be another source of vaccine hesitancy among members of the general population that physicians need to address. In a survey of almost 3,500 health care workers conducted in October and November 2020 and published in January 2021 in Vaccines, only about a third (36%) said they would get the vaccine as soon as it became available. By mid- to late-February, 54% of health care workers reported having been vaccinated and another 10% planned to get the vaccine as soon as possible, according to the Kaiser Family Foundation COVID-19 Vaccine Monitor.

Resolving doubts about the vaccines requires a thoughtful approach toward health care colleagues, said Eileen Barrett, MD, MPH, an internist and hospitalist who was a coauthor of the Vaccines paper and who serves on the editorial advisory board of Internal Medicine News. “We should meet people where they are and do our best to hear their concerns, listening thoughtfully without condescension. Validate how important their role is in endorsing vaccination and also validate asking questions.”

There’s power in the strong personal testimonial of physicians and other health care workers – not just to influence patients, but as a model for fellow health professionals, as well, noted Dr. Barrett, who cares for COVID-19 patients and is associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.
 

‘Do it for your loved ones’

The Reagan-Udall Foundation, a nonprofit organization created by Congress to support the Food and Drug Administration, tested some messaging with focus groups. Participants responded favorably to this statement about why the vaccines were developed so quickly: “Vaccine development moved faster than normal because everyone’s making it their highest priority.”

People did not feel motivated to get the vaccine out of a sense of civic duty, said Susan Winckler, RPh, Esq, who is CEO of the foundation. But they did think the following was a good reason to get vaccinated: “By getting a vaccine, I could protect my children, my parents, and other loved ones.”

Physicians also can work with community influencers, such as faith leaders, to build confidence in vaccines. That’s part of the strategy of Roll Up Your Sleeves, a campaign spearheaded by agilon health, a company that partners with physician practices to develop value-based care for Medicare Advantage patients.

For example, Wilmington Health in North Carolina answered questions about the vaccines in Facebook Live events and created a Spanish-language video to boost vaccine confidence in the Latinx community. Additionally, PriMED Physicians in Dayton, Ohio, reached out to Black churches to provide a vaccine-awareness video and a PriMED doctor participated in a webinar sponsored by the Nigerian Women Cultural Organization to help dispel myths about COVID-19 and the vaccines.

“This is a way to deepen our relationship with our patients,” said Ben Kornitzer, MD, chief medical officer of agilon. “It’s helping to walk them through this door where on one side is the pandemic and social isolation and on the other side is a return to their life and loved ones.”

The messages provided by primary care physicians can be powerful and affirming, said Ms. Winckler.

“The path forward is to make a space for people to ask questions,” she continued, noting that the Reagan-Udall Foundation provides charts that show how the timeline for vaccine development was compressed without skipping any steps.

Strategies and background information on how to reinforce confidence in COVID-19 vaccines are also available on a page of the Centers for Disease Control and Prevention’s website.

None of the experts interviewed reported any relevant conflicts of interest. The Reagan-Udall Foundation has received sponsorships from Johnson & Johnson and AstraZeneca and has had a safety surveillance contract with Pfizer.

Family physician Mitchell A. Kaminski, MD, MBA, was still awash in feelings of joy and relief at recently being vaccinated against COVID-19 when a patient’s comments stopped him cold. The patient, a middle-aged man with several comorbidities had just declined the pneumonia vaccine – and he added, without prompting, that he wouldn’t be getting the COVID vaccine either. This patient had heard getting vaccinated could kill him.

Dr. Kaminski countered with medical facts, including that the very rare side effects hadn’t killed anyone in the United States but COVID was killing thousands of people every day. “Well then, I’ll just risk getting COVID,” Dr. Kaminski recalled the patient saying. Conversation over.

That experience caused Dr. Kaminski, who is program director for population health at Thomas Jefferson University, Philadelphia, to rethink the way he talks to patients who are uncertain or skeptical about getting a COVID-19 vaccine. Now, if he saw that patient who seemed fearful of dying from a vaccination, Dr. Kaminski said he would be more curious.

Instead of outright contradicting the beliefs of a patient who is reluctant to get vaccinated, Dr. Kaminski now gently asks about the reasons for their discomfort and offers information about the vaccines. But mostly, he listens.

©Sean Warren/iStockphoto.com

Conversations between physicians and patients about the risks that come with getting a COVID-19 vaccine are becoming more common in general as eligibility for immunizations expands. Physicians are using a variety of methods to communicate about the safety and importance of getting vaccinated that they think will lead to more of their patients getting a COVID-19 vaccine.

About 80% of Americans say that they are most likely to turn to doctors, nurses and other health professionals for help in deciding whether to get the COVID vaccine, according to research by the Kaiser Family Foundation.
 

Getting beyond the distrust

While patients often feel a strong connection with their health providers, distrust in the medical establishment still exists, especially among some populations. The Kaiser Family Foundation reported that a third of Black respondents are taking a “wait-and-see” approach, while 23% said they will get it only if it’s required – or not at all.

Distrust persists from historical racist events in medicine, such as the infamous Tuskegee experiments in which treatment was withheld from Black men with syphilis. But physicians shouldn’t assume that all Black patients have the same reasons for vaccine hesitancy, said Krys Foster, MD, MPH, a family physician at Thomas Jefferson University.

“In my experience caring for patients who are uncertain or have concerns about receiving the vaccine, I’ve learned that many are just seeking more information, or even my approval to say that it is safe to proceed given their medical history,” she said.

Sources such as the COVID Racial Data Tracker have found that Black Americans have a higher COVID death rate than other racial or ethnic groups, making vaccination even more vital. Yet fear of the vaccine could be triggered by misinformation that can be found in various places online, Dr. Foster said.

To encourage people to get vaccinated and dispel false information, Dr. Foster takes time to discuss how safe it is to get a COVID-19 vaccine and the vaccines’ side effects, then quickly pivots to discussing how to get vaccinated.

It can be difficult for some people to find appointments or access testing sites. The failure to get the vaccine shouldn’t automatically be attributed to “hesitancy,” she said. “The onus is on the medical community to help fix the health injustices inflicted on communities of color by providing equitable information and access and stop placing blame on them for having the ‘wrong’ vaccine attitude.”
 

Give your testimonial

Jamie Loehr, MD, of Cayuga Family Medicine in Ithaca, N.Y., said he has always had a higher-than-average number of patients who refused or delayed their children’s vaccines. He does not kick them out of his practice but politely continues to educate them about the vaccines.

When patients ask Dr. Loehr if he trusts the vaccine, he responds with confidence: “I not only believe in it, I got it and I recommend it to anyone who can possibly get it.”

He was surprised recently when a mother who has expressed reluctance to vaccinate her young children came for a checkup and told him she had already received a COVID vaccine. “She made the decision on her own that this was important enough that she wanted to get it,” he said.
 

Health care worker hesitancy

Some health care workers’ unease about being at the front of the line for vaccines may be another source of vaccine hesitancy among members of the general population that physicians need to address. In a survey of almost 3,500 health care workers conducted in October and November 2020 and published in January 2021 in Vaccines, only about a third (36%) said they would get the vaccine as soon as it became available. By mid- to late-February, 54% of health care workers reported having been vaccinated and another 10% planned to get the vaccine as soon as possible, according to the Kaiser Family Foundation COVID-19 Vaccine Monitor.

Resolving doubts about the vaccines requires a thoughtful approach toward health care colleagues, said Eileen Barrett, MD, MPH, an internist and hospitalist who was a coauthor of the Vaccines paper and who serves on the editorial advisory board of Internal Medicine News. “We should meet people where they are and do our best to hear their concerns, listening thoughtfully without condescension. Validate how important their role is in endorsing vaccination and also validate asking questions.”

There’s power in the strong personal testimonial of physicians and other health care workers – not just to influence patients, but as a model for fellow health professionals, as well, noted Dr. Barrett, who cares for COVID-19 patients and is associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.
 

‘Do it for your loved ones’

The Reagan-Udall Foundation, a nonprofit organization created by Congress to support the Food and Drug Administration, tested some messaging with focus groups. Participants responded favorably to this statement about why the vaccines were developed so quickly: “Vaccine development moved faster than normal because everyone’s making it their highest priority.”

People did not feel motivated to get the vaccine out of a sense of civic duty, said Susan Winckler, RPh, Esq, who is CEO of the foundation. But they did think the following was a good reason to get vaccinated: “By getting a vaccine, I could protect my children, my parents, and other loved ones.”

Physicians also can work with community influencers, such as faith leaders, to build confidence in vaccines. That’s part of the strategy of Roll Up Your Sleeves, a campaign spearheaded by agilon health, a company that partners with physician practices to develop value-based care for Medicare Advantage patients.

For example, Wilmington Health in North Carolina answered questions about the vaccines in Facebook Live events and created a Spanish-language video to boost vaccine confidence in the Latinx community. Additionally, PriMED Physicians in Dayton, Ohio, reached out to Black churches to provide a vaccine-awareness video and a PriMED doctor participated in a webinar sponsored by the Nigerian Women Cultural Organization to help dispel myths about COVID-19 and the vaccines.

“This is a way to deepen our relationship with our patients,” said Ben Kornitzer, MD, chief medical officer of agilon. “It’s helping to walk them through this door where on one side is the pandemic and social isolation and on the other side is a return to their life and loved ones.”

The messages provided by primary care physicians can be powerful and affirming, said Ms. Winckler.

“The path forward is to make a space for people to ask questions,” she continued, noting that the Reagan-Udall Foundation provides charts that show how the timeline for vaccine development was compressed without skipping any steps.

Strategies and background information on how to reinforce confidence in COVID-19 vaccines are also available on a page of the Centers for Disease Control and Prevention’s website.

None of the experts interviewed reported any relevant conflicts of interest. The Reagan-Udall Foundation has received sponsorships from Johnson & Johnson and AstraZeneca and has had a safety surveillance contract with Pfizer.