MDedge Pediatrics

The drug alpha-difluoromethylornithine (DFMO) may help preserve beta-cell function in people with new-onset type 1 diabetes, new preliminary data suggest.

“I think we have lots of potential to improve people’s quality of life who are living with type 1 diabetes if we can increase their endogenous insulin secretion. ... I think long-term combination therapy is going to be the answer,” study author Emily K. Sims, MD, a pediatric endocrinologist at Indiana University, Indianapolis, said in an interview.

DFMO inhibits the polyamine biosynthesis pathway, which plays a role in the inflammatory responses in autoimmune diseases, including type 1 diabetes. It’s sold under the name eflornithine as an intravenous treatment for African sleeping sickness (trypanosomiasis) and as a cream for unwanted hair growth in women. It also has orphan designations for treating various cancers, including neuroblastoma.

In type 1 diabetes, the immune system destroys insulin-producing pancreatic beta cells. Insulin treatment is required. Recently, the monoclonal antibody teplizumab (Tzield, Sanofi) was approved as a treatment for delaying the onset of type 1 diabetes in people with autoantibodies that signify a preclinical stage of the condition. As yet, no agent has been approved for preserving beta-cell function after the onset of type 1 diabetes, but many are under investigation.

The new safety study by Dr. Sims and colleagues, which was published in Cell Medicine Reports, enrolled 41 people with type 1 diabetes who had been diagnosed within the previous 8 months, including 31 children. Participants were randomly assigned to undergo oral treatment with DFMO at one of five doses or placebo for 3 months, with 3 additional months of follow-up.

Following a mixed-meal tolerance test at 6 months, the C-peptide area under the curve – a measure of beta-cell function – was significantly higher with the three highest DFMO doses compared to placebo (P = .02, .03, and .02 for 125 mg/m², 750 mg/m², and 1,000 mg/m², respectively).

Two individuals dropped out, one because of anaphylaxis. There were no dose-limiting toxicities or serious adverse events, while mild gastrointestinal events, anemia, and headache were common. “Although there’s no [Food and Drug Administration] approval for the oral form right now, there’s a lot of safety data, including in kids from the neuroblastoma studies,” Dr. Sims explained.

There were no differences in C-peptide at 3 months or in hemoglobin A1c at any time point. Glucose areas under the curve were significantly lower for DFMO, compared with placebo in the 125-mg/m² and 750-mg/m² treatment groups at the 6-month time point (P = .03 and .04, respectively).

In their article, Dr. Sims and colleagues also reported confirmatory analyses in mice, as well as testing in the humans showing that there didn’t appear to be significant immune system modulation. “So, we can envision giving DFMO in addition to something that targets the immune system, as a combination therapy,” said Dr. Sims, who also worked on the pivotal study of teplizumab.

“I’m excited. The sample size is small, so I was kind of expecting no efficacy signals. ... It’s definitely worth following up,” she said.

However, she noted, “it wasn’t a slam-dunk huge effect. It was subtle. It seemed that things were kind of more stable compared to placebo over time versus ... a big increase in C-peptide over time.”

But, she added, “I believe that even teplizumab will need to be used in combination. It delays the onset of type 1 diabetes and improves C-peptide, but it didn’t get everyone off insulin. I don’t think we’ve seen any drug that won’t need to be used in combination.”

Dr. Sims pointed to other investigational agents, such as verapamil and various Janus kinase inhibitors, that may also serve in combination to forestall or reduce insulin dependency for people with either new-onset type 1 diabetes or those who have been identified via screening as having type 1 diabetes–related autoantibodies. “I think there are a lot of potential different interventions.”

Dr. Sims and colleagues are now conducting a larger six-center JDRF-funded study of DFMO in early-onset type 1 diabetes that will be fully powered and that will use the highest tolerated doses from the preliminary study.

She believes there will likely be benefit even if the agent doesn’t completely reverse the disease. “The people who are making more insulin are just easier to manage, with more time in range and less hypoglycemia.” Even if the drugs only delay but don’t prevent type 1 diabetes entirely in those at risk, “the improvement in quality of life of being able to delay insulin for a few years is really palpable. ... I’m really optimistic.”

Dr. Sims disclosed no relevant financial relationships. Three other authors are coauthors on a patent application for the use of DFMO for the treatment of beta-cell dysfunction in type 1 diabetes; one of those three authors is an employee of Cancer Prevention Pharmaceuticals.

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

The drug alpha-difluoromethylornithine (DFMO) may help preserve beta-cell function in people with new-onset type 1 diabetes, new preliminary data suggest.

“I think we have lots of potential to improve people’s quality of life who are living with type 1 diabetes if we can increase their endogenous insulin secretion. ... I think long-term combination therapy is going to be the answer,” study author Emily K. Sims, MD, a pediatric endocrinologist at Indiana University, Indianapolis, said in an interview.

DFMO inhibits the polyamine biosynthesis pathway, which plays a role in the inflammatory responses in autoimmune diseases, including type 1 diabetes. It’s sold under the name eflornithine as an intravenous treatment for African sleeping sickness (trypanosomiasis) and as a cream for unwanted hair growth in women. It also has orphan designations for treating various cancers, including neuroblastoma.

In type 1 diabetes, the immune system destroys insulin-producing pancreatic beta cells. Insulin treatment is required. Recently, the monoclonal antibody teplizumab (Tzield, Sanofi) was approved as a treatment for delaying the onset of type 1 diabetes in people with autoantibodies that signify a preclinical stage of the condition. As yet, no agent has been approved for preserving beta-cell function after the onset of type 1 diabetes, but many are under investigation.

The new safety study by Dr. Sims and colleagues, which was published in Cell Medicine Reports, enrolled 41 people with type 1 diabetes who had been diagnosed within the previous 8 months, including 31 children. Participants were randomly assigned to undergo oral treatment with DFMO at one of five doses or placebo for 3 months, with 3 additional months of follow-up.

Following a mixed-meal tolerance test at 6 months, the C-peptide area under the curve – a measure of beta-cell function – was significantly higher with the three highest DFMO doses compared to placebo (P = .02, .03, and .02 for 125 mg/m², 750 mg/m², and 1,000 mg/m², respectively).

Two individuals dropped out, one because of anaphylaxis. There were no dose-limiting toxicities or serious adverse events, while mild gastrointestinal events, anemia, and headache were common. “Although there’s no [Food and Drug Administration] approval for the oral form right now, there’s a lot of safety data, including in kids from the neuroblastoma studies,” Dr. Sims explained.

There were no differences in C-peptide at 3 months or in hemoglobin A1c at any time point. Glucose areas under the curve were significantly lower for DFMO, compared with placebo in the 125-mg/m² and 750-mg/m² treatment groups at the 6-month time point (P = .03 and .04, respectively).

In their article, Dr. Sims and colleagues also reported confirmatory analyses in mice, as well as testing in the humans showing that there didn’t appear to be significant immune system modulation. “So, we can envision giving DFMO in addition to something that targets the immune system, as a combination therapy,” said Dr. Sims, who also worked on the pivotal study of teplizumab.

“I’m excited. The sample size is small, so I was kind of expecting no efficacy signals. ... It’s definitely worth following up,” she said.

However, she noted, “it wasn’t a slam-dunk huge effect. It was subtle. It seemed that things were kind of more stable compared to placebo over time versus ... a big increase in C-peptide over time.”

But, she added, “I believe that even teplizumab will need to be used in combination. It delays the onset of type 1 diabetes and improves C-peptide, but it didn’t get everyone off insulin. I don’t think we’ve seen any drug that won’t need to be used in combination.”

Dr. Sims pointed to other investigational agents, such as verapamil and various Janus kinase inhibitors, that may also serve in combination to forestall or reduce insulin dependency for people with either new-onset type 1 diabetes or those who have been identified via screening as having type 1 diabetes–related autoantibodies. “I think there are a lot of potential different interventions.”

Dr. Sims and colleagues are now conducting a larger six-center JDRF-funded study of DFMO in early-onset type 1 diabetes that will be fully powered and that will use the highest tolerated doses from the preliminary study.

She believes there will likely be benefit even if the agent doesn’t completely reverse the disease. “The people who are making more insulin are just easier to manage, with more time in range and less hypoglycemia.” Even if the drugs only delay but don’t prevent type 1 diabetes entirely in those at risk, “the improvement in quality of life of being able to delay insulin for a few years is really palpable. ... I’m really optimistic.”

Dr. Sims disclosed no relevant financial relationships. Three other authors are coauthors on a patent application for the use of DFMO for the treatment of beta-cell dysfunction in type 1 diabetes; one of those three authors is an employee of Cancer Prevention Pharmaceuticals.

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

The drug alpha-difluoromethylornithine (DFMO) may help preserve beta-cell function in people with new-onset type 1 diabetes, new preliminary data suggest.

“I think we have lots of potential to improve people’s quality of life who are living with type 1 diabetes if we can increase their endogenous insulin secretion. ... I think long-term combination therapy is going to be the answer,” study author Emily K. Sims, MD, a pediatric endocrinologist at Indiana University, Indianapolis, said in an interview.

DFMO inhibits the polyamine biosynthesis pathway, which plays a role in the inflammatory responses in autoimmune diseases, including type 1 diabetes. It’s sold under the name eflornithine as an intravenous treatment for African sleeping sickness (trypanosomiasis) and as a cream for unwanted hair growth in women. It also has orphan designations for treating various cancers, including neuroblastoma.

In type 1 diabetes, the immune system destroys insulin-producing pancreatic beta cells. Insulin treatment is required. Recently, the monoclonal antibody teplizumab (Tzield, Sanofi) was approved as a treatment for delaying the onset of type 1 diabetes in people with autoantibodies that signify a preclinical stage of the condition. As yet, no agent has been approved for preserving beta-cell function after the onset of type 1 diabetes, but many are under investigation.

The new safety study by Dr. Sims and colleagues, which was published in Cell Medicine Reports, enrolled 41 people with type 1 diabetes who had been diagnosed within the previous 8 months, including 31 children. Participants were randomly assigned to undergo oral treatment with DFMO at one of five doses or placebo for 3 months, with 3 additional months of follow-up.

Following a mixed-meal tolerance test at 6 months, the C-peptide area under the curve – a measure of beta-cell function – was significantly higher with the three highest DFMO doses compared to placebo (P = .02, .03, and .02 for 125 mg/m², 750 mg/m², and 1,000 mg/m², respectively).

Two individuals dropped out, one because of anaphylaxis. There were no dose-limiting toxicities or serious adverse events, while mild gastrointestinal events, anemia, and headache were common. “Although there’s no [Food and Drug Administration] approval for the oral form right now, there’s a lot of safety data, including in kids from the neuroblastoma studies,” Dr. Sims explained.

There were no differences in C-peptide at 3 months or in hemoglobin A1c at any time point. Glucose areas under the curve were significantly lower for DFMO, compared with placebo in the 125-mg/m² and 750-mg/m² treatment groups at the 6-month time point (P = .03 and .04, respectively).

In their article, Dr. Sims and colleagues also reported confirmatory analyses in mice, as well as testing in the humans showing that there didn’t appear to be significant immune system modulation. “So, we can envision giving DFMO in addition to something that targets the immune system, as a combination therapy,” said Dr. Sims, who also worked on the pivotal study of teplizumab.

“I’m excited. The sample size is small, so I was kind of expecting no efficacy signals. ... It’s definitely worth following up,” she said.

However, she noted, “it wasn’t a slam-dunk huge effect. It was subtle. It seemed that things were kind of more stable compared to placebo over time versus ... a big increase in C-peptide over time.”

But, she added, “I believe that even teplizumab will need to be used in combination. It delays the onset of type 1 diabetes and improves C-peptide, but it didn’t get everyone off insulin. I don’t think we’ve seen any drug that won’t need to be used in combination.”

Dr. Sims pointed to other investigational agents, such as verapamil and various Janus kinase inhibitors, that may also serve in combination to forestall or reduce insulin dependency for people with either new-onset type 1 diabetes or those who have been identified via screening as having type 1 diabetes–related autoantibodies. “I think there are a lot of potential different interventions.”

Dr. Sims and colleagues are now conducting a larger six-center JDRF-funded study of DFMO in early-onset type 1 diabetes that will be fully powered and that will use the highest tolerated doses from the preliminary study.

She believes there will likely be benefit even if the agent doesn’t completely reverse the disease. “The people who are making more insulin are just easier to manage, with more time in range and less hypoglycemia.” Even if the drugs only delay but don’t prevent type 1 diabetes entirely in those at risk, “the improvement in quality of life of being able to delay insulin for a few years is really palpable. ... I’m really optimistic.”

Dr. Sims disclosed no relevant financial relationships. Three other authors are coauthors on a patent application for the use of DFMO for the treatment of beta-cell dysfunction in type 1 diabetes; one of those three authors is an employee of Cancer Prevention Pharmaceuticals.

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

For preventing rejection of cardiac transplants in children, the combination of everolimus and low-dose tacrolimus should now be considered an alternative to mycophenolate mofetil (MMF) plus standard-dose tacrolimus, according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.

Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.

Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.

In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
 

Everolimus- vs. MMF-based antirejection

The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m² every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).

In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).

The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).

Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
 

Numerical advantage for everolimus on efficacy

The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.

Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.

On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.

In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).

Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).

Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
 

Study supports safety of everolimus regimen

The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.

However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.

“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.

Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.

He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.

Early mortality based on infection “was not observed in our study,” he said.

The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.

Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,

Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.

For preventing rejection of cardiac transplants in children, the combination of everolimus and low-dose tacrolimus should now be considered an alternative to mycophenolate mofetil (MMF) plus standard-dose tacrolimus, according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.

Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.

Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.

In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
 

Everolimus- vs. MMF-based antirejection

The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m² every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).

In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).

The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).

Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
 

Numerical advantage for everolimus on efficacy

The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.

Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.

On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.

In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).

Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).

Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
 

Study supports safety of everolimus regimen

The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.

However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.

“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.

Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.

He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.

Early mortality based on infection “was not observed in our study,” he said.

The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.

Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,

Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.

For preventing rejection of cardiac transplants in children, the combination of everolimus and low-dose tacrolimus should now be considered an alternative to mycophenolate mofetil (MMF) plus standard-dose tacrolimus, according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.

Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.

Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.

In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
 

Everolimus- vs. MMF-based antirejection

The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m² every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).

In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).

The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).

Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
 

Numerical advantage for everolimus on efficacy

The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.

Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.

On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.

In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).

Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).

Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
 

Study supports safety of everolimus regimen

The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.

However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.

“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.

Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.

He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.

Early mortality based on infection “was not observed in our study,” he said.

The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.

Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,

Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.

In a recently published Medscape report, 26% of American physicians said they were considering a career away from practicing medicine, for various reasons. Becoming a teacher was one of the nonclinical careers that most enthused them. What were the others?

This infographic shows the five potential new careers that most interested U.S. physicians considering a change. For more details, check out the Medscape Physicians and Nonclinical Careers Report 2023.

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

In a recently published Medscape report, 26% of American physicians said they were considering a career away from practicing medicine, for various reasons. Becoming a teacher was one of the nonclinical careers that most enthused them. What were the others?

This infographic shows the five potential new careers that most interested U.S. physicians considering a change. For more details, check out the Medscape Physicians and Nonclinical Careers Report 2023.

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

In a recently published Medscape report, 26% of American physicians said they were considering a career away from practicing medicine, for various reasons. Becoming a teacher was one of the nonclinical careers that most enthused them. What were the others?

This infographic shows the five potential new careers that most interested U.S. physicians considering a change. For more details, check out the Medscape Physicians and Nonclinical Careers Report 2023.

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

Fecal transplants are safe and effective treatments for recurrent Clostridioides difficile infections in children, according to a clinical report released by the American Academy of Pediatrics (AAP).

However, fecal microbiota transplants (FMTs) should not be used to treat other gastrointestinal ailments such as Crohn’s disease or ulcerative colitis, because scientific evidence falls short on effectiveness in treating these conditions, the group said.

C. difficile infections (CDIs) are major contributors to hospital-associated diarrhea and diarrhea caused by antibiotics. An FMT involves introducing the feces of a healthy person into the gastrointestinal tract, usually through a nasogastric tube but sometimes in capsules containing healthy stool. Serious adverse reactions associated with an FMT, such as hospitalization, are rare, occuring in roughly 2% of case, the AAP said.

An FMT “does have a place for treatment of recurrent CDIs in children,” said Maria Oliva-Hemker, MD, a pediatric gastroenterologist at Johns Hopkins University School of Medicine in Baltimore and the lead author of the report, which was online in Pediatrics.

The AAP strongly encourages people not to perform an FMT at home, although caregivers may be tempted due to a lack of medical facilities located nearby to deliver this care.

“People might see a video on YouTube and think they can do this themselves,” Dr. Oliva-Hemker said.

An FMT requires screening of donors for any infections, which involves administering questionnaires and analyzing donor blood and stool, which are tasks better suited for medical facilities than for a living room.

No controlled or prospective clinical trials on the efficacy of FMT for children exist, according to the AAP. But a retrospective study published in 2020 showed that one or two courses of FMT prevented CDI recurrence in children 87% of the time. Researchers defined the eradication of CDIs as no recurrence for at least 2 months after an FMT and noted the success rates in children were comaparable to those reported in adults.

Unlike pediatric data, adult data come from a randomized clinical trial.

“Sometimes, kids are the last people to be enrolled in these trials,” said Maribeth Nicholson, MD, MPH, a pediatric gastroenterologist at Vanderbilt University Medical Center in Nashville, Tenn., an author of the 2020 study. 

Dr. Nicholson, who was not involved in the AAP report, said that the retrospective data are strong enough to justify using FMT to eradicate CDIs in children. But researchers are unclear about the biologic mechanisms that make FMTs work. 

Dr. Nicholson said that many therapeutics meant to produce a healthier microbiome are being studied in clinical trials. Any clinical trials of such products should include children, Dr. Nicholson said. A child’s gastrointestinal microbiome is actively developing, Dr. Nicholson added, compared with the relatively stable microbiome of an adult. 

“When we think about the microbiome it makes sense to target kids, because they’re more apt to respond to these therapies. I worry that somebody will say ‘this doesn’t work in adults,’ and it just stops there,” Dr. Nicholson said.

Though the AAP said that the benefits of FMT for treating CDIs are clear, the data available for treating other conditions such as ulcerative colitis or Crohn’s disease are less convincing. Any child receiving an FMT for these ailments should only do so as part of a clinical trial, the group said.

The AAP report endorses a joint position paper, published in 2019, about the benefits of FMTs for CDIs from North American and European pediatric gastroenterology societies. Dr. Nicholson was an author of this joint statement and hopes that the AAP report raises further awareness among pediatricians that FMTs are a safe and effective treatment for recurrent CDIs.

“This is something that maybe is not as discussed in pediatric circles. Kids need FMTs sometimes,” Dr. Nicholson said.

Dr. Oliva-Hemker and Dr. Nicholson report no relevant financial relationships.


A version of this article appeared on Medscape.com.

Fecal transplants are safe and effective treatments for recurrent Clostridioides difficile infections in children, according to a clinical report released by the American Academy of Pediatrics (AAP).

However, fecal microbiota transplants (FMTs) should not be used to treat other gastrointestinal ailments such as Crohn’s disease or ulcerative colitis, because scientific evidence falls short on effectiveness in treating these conditions, the group said.

C. difficile infections (CDIs) are major contributors to hospital-associated diarrhea and diarrhea caused by antibiotics. An FMT involves introducing the feces of a healthy person into the gastrointestinal tract, usually through a nasogastric tube but sometimes in capsules containing healthy stool. Serious adverse reactions associated with an FMT, such as hospitalization, are rare, occuring in roughly 2% of case, the AAP said.

An FMT “does have a place for treatment of recurrent CDIs in children,” said Maria Oliva-Hemker, MD, a pediatric gastroenterologist at Johns Hopkins University School of Medicine in Baltimore and the lead author of the report, which was online in Pediatrics.

The AAP strongly encourages people not to perform an FMT at home, although caregivers may be tempted due to a lack of medical facilities located nearby to deliver this care.

“People might see a video on YouTube and think they can do this themselves,” Dr. Oliva-Hemker said.

An FMT requires screening of donors for any infections, which involves administering questionnaires and analyzing donor blood and stool, which are tasks better suited for medical facilities than for a living room.

No controlled or prospective clinical trials on the efficacy of FMT for children exist, according to the AAP. But a retrospective study published in 2020 showed that one or two courses of FMT prevented CDI recurrence in children 87% of the time. Researchers defined the eradication of CDIs as no recurrence for at least 2 months after an FMT and noted the success rates in children were comaparable to those reported in adults.

Unlike pediatric data, adult data come from a randomized clinical trial.

“Sometimes, kids are the last people to be enrolled in these trials,” said Maribeth Nicholson, MD, MPH, a pediatric gastroenterologist at Vanderbilt University Medical Center in Nashville, Tenn., an author of the 2020 study. 

Dr. Nicholson, who was not involved in the AAP report, said that the retrospective data are strong enough to justify using FMT to eradicate CDIs in children. But researchers are unclear about the biologic mechanisms that make FMTs work. 

Dr. Nicholson said that many therapeutics meant to produce a healthier microbiome are being studied in clinical trials. Any clinical trials of such products should include children, Dr. Nicholson said. A child’s gastrointestinal microbiome is actively developing, Dr. Nicholson added, compared with the relatively stable microbiome of an adult. 

“When we think about the microbiome it makes sense to target kids, because they’re more apt to respond to these therapies. I worry that somebody will say ‘this doesn’t work in adults,’ and it just stops there,” Dr. Nicholson said.

Though the AAP said that the benefits of FMT for treating CDIs are clear, the data available for treating other conditions such as ulcerative colitis or Crohn’s disease are less convincing. Any child receiving an FMT for these ailments should only do so as part of a clinical trial, the group said.

The AAP report endorses a joint position paper, published in 2019, about the benefits of FMTs for CDIs from North American and European pediatric gastroenterology societies. Dr. Nicholson was an author of this joint statement and hopes that the AAP report raises further awareness among pediatricians that FMTs are a safe and effective treatment for recurrent CDIs.

“This is something that maybe is not as discussed in pediatric circles. Kids need FMTs sometimes,” Dr. Nicholson said.

Dr. Oliva-Hemker and Dr. Nicholson report no relevant financial relationships.


A version of this article appeared on Medscape.com.

Fecal transplants are safe and effective treatments for recurrent Clostridioides difficile infections in children, according to a clinical report released by the American Academy of Pediatrics (AAP).

However, fecal microbiota transplants (FMTs) should not be used to treat other gastrointestinal ailments such as Crohn’s disease or ulcerative colitis, because scientific evidence falls short on effectiveness in treating these conditions, the group said.

C. difficile infections (CDIs) are major contributors to hospital-associated diarrhea and diarrhea caused by antibiotics. An FMT involves introducing the feces of a healthy person into the gastrointestinal tract, usually through a nasogastric tube but sometimes in capsules containing healthy stool. Serious adverse reactions associated with an FMT, such as hospitalization, are rare, occuring in roughly 2% of case, the AAP said.

An FMT “does have a place for treatment of recurrent CDIs in children,” said Maria Oliva-Hemker, MD, a pediatric gastroenterologist at Johns Hopkins University School of Medicine in Baltimore and the lead author of the report, which was online in Pediatrics.

The AAP strongly encourages people not to perform an FMT at home, although caregivers may be tempted due to a lack of medical facilities located nearby to deliver this care.

“People might see a video on YouTube and think they can do this themselves,” Dr. Oliva-Hemker said.

An FMT requires screening of donors for any infections, which involves administering questionnaires and analyzing donor blood and stool, which are tasks better suited for medical facilities than for a living room.

No controlled or prospective clinical trials on the efficacy of FMT for children exist, according to the AAP. But a retrospective study published in 2020 showed that one or two courses of FMT prevented CDI recurrence in children 87% of the time. Researchers defined the eradication of CDIs as no recurrence for at least 2 months after an FMT and noted the success rates in children were comaparable to those reported in adults.

Unlike pediatric data, adult data come from a randomized clinical trial.

“Sometimes, kids are the last people to be enrolled in these trials,” said Maribeth Nicholson, MD, MPH, a pediatric gastroenterologist at Vanderbilt University Medical Center in Nashville, Tenn., an author of the 2020 study. 

Dr. Nicholson, who was not involved in the AAP report, said that the retrospective data are strong enough to justify using FMT to eradicate CDIs in children. But researchers are unclear about the biologic mechanisms that make FMTs work. 

Dr. Nicholson said that many therapeutics meant to produce a healthier microbiome are being studied in clinical trials. Any clinical trials of such products should include children, Dr. Nicholson said. A child’s gastrointestinal microbiome is actively developing, Dr. Nicholson added, compared with the relatively stable microbiome of an adult. 

“When we think about the microbiome it makes sense to target kids, because they’re more apt to respond to these therapies. I worry that somebody will say ‘this doesn’t work in adults,’ and it just stops there,” Dr. Nicholson said.

Though the AAP said that the benefits of FMT for treating CDIs are clear, the data available for treating other conditions such as ulcerative colitis or Crohn’s disease are less convincing. Any child receiving an FMT for these ailments should only do so as part of a clinical trial, the group said.

The AAP report endorses a joint position paper, published in 2019, about the benefits of FMTs for CDIs from North American and European pediatric gastroenterology societies. Dr. Nicholson was an author of this joint statement and hopes that the AAP report raises further awareness among pediatricians that FMTs are a safe and effective treatment for recurrent CDIs.

“This is something that maybe is not as discussed in pediatric circles. Kids need FMTs sometimes,” Dr. Nicholson said.

Dr. Oliva-Hemker and Dr. Nicholson report no relevant financial relationships.


A version of this article appeared on Medscape.com.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

Money talks.

The United States faces a serious shortage of primary care physicians for many reasons, but one, in particular, is inescapable: compensation.

Substantial disparities between what primary care physicians earn relative to specialists like orthopedists and cardiologists can weigh into medical students’ decisions about which field to choose. Plus, the system that Medicare and other health plans use to pay doctors generally places more value on doing procedures like replacing a knee or inserting a stent than on delivering the whole-person, long-term health care management that primary care physicians provide.

As a result of those pay disparities, and the punishing workload typically faced by primary care physicians, more new doctors are becoming specialists, often leaving patients with fewer choices for primary care.

“There is a public out there that is dissatisfied with the lack of access to a routine source of care,” said Christopher Koller, president of the Milbank Memorial Fund, a foundation that focuses on improving population health and health equity. “That’s not going to be addressed until we pay for it.”

Primary care is the foundation of our health care system, the only area in which providing more services – such as childhood vaccines and regular blood pressure screenings – is linked to better population health and more equitable outcomes, according to the National Academies of Sciences, Engineering, and Medicine, in a recently published report on how to rebuild primary care. Without it, the national academies wrote, “minor health problems can spiral into chronic disease,” with poor disease management, ED overuse, and unsustainable costs. Yet for decades, the United States has underinvested in primary care. It accounted for less than 5% of health care spending in 2020 – significantly less than the average spending by countries that are members of the Organization for Economic Cooperation and Development, according to the report.

A $26 billion piece of bipartisan legislation proposed last month by Sen. Bernie Sanders (I-Vt.), chair of the Senate Health, Education, Labor, and Pensions Committee, and Sen. Roger Marshall (R-Kan.) would bolster primary care by increasing training opportunities for doctors and nurses and expanding access to community health centers. Policy experts say the bill would provide important support, but it’s not enough. It doesn’t touch compensation.

“We need primary care to be paid differently and to be paid more, and that starts with Medicare,” Mr. Koller said.
 

How Medicare drives payment

Medicare, which covers 65 million people who are 65 and older or who have certain long-term disabilities, finances more than a fifth of all health care spending — giving it significant muscle in the health care market. Private health plans typically base their payment amounts on the Medicare system, so what Medicare pays is crucial.

Under the Medicare payment system, the amount the program pays for a medical service is determined by three geographically weighted components: a physician’s work, including time and intensity; the practice’s expense, such as overhead and equipment; and professional insurance. It tends to reward specialties that emphasize procedures, such as repairing a hernia or removing a tumor, more than primary care, where the focus is on talking with patients, answering questions, and educating them about managing their chronic conditions.

Medical students may not be familiar with the particulars of how the payment system works, but their clinical training exposes them to a punishing workload and burnout that is contributing to the shortage of primary care physicians, projected to reach up to 48,000 by 2034, according to estimates from the Association of American Medical Colleges.

The earnings differential between primary care and other specialists is also not lost on them. Average annual compensation for doctors who focus on primary care – family medicine, internists, and pediatricians – ranges from an average of about $250,000 to $275,000, according to Medscape’s annual physician compensation report. Many specialists make more than twice as much: Plastic surgeons top the compensation list at $619,000 annually, followed by orthopedists ($573,000) and cardiologists ($507,000).

“I think the major issues in terms of the primary care physician pipeline are the compensation and the work of primary care,” said Russ Phillips, MD, an internist and the director of the Harvard Medical School Center for Primary Care, Boston. “You have to really want to be a primary care physician when that student will make one-third of what students going into dermatology will make.”

According to statistics from the National Resident Matching Program, which tracks the number of residency slots available for graduating medical students and the number of slots filled, 89% of 5,088 family medicine residency slots were filled in 2023, compared with a 93% residency fill rate overall. Internists had a higher fill rate, 96%, but a significant proportion of internal medicine residents eventually practice in a specialty area rather than in primary care.

No one would claim that doctors are poorly paid, but with the average medical student graduating with just over $200,000 in medical school debt, making a good salary matters.
 

Not in it for the money

Still, it’s a misperception that student debt always drives the decision whether to go into primary care, said Len Marquez, senior director of government relations and legislative advocacy at the Association of American Medical Colleges.

For Anitza Quintero, 24, a second-year medical student at the Geisinger Commonwealth School of Medicine in rural Pennsylvania, primary care is a logical extension of her interest in helping children and immigrants. Ms. Quintero’s family came to the United States on a raft from Cuba before she was born. She plans to focus on internal medicine and pediatrics.

“I want to keep going to help my family and other families,” Ms. Quintero said. “There’s obviously something attractive about having a specialty and a high pay grade,” Still, she wants to work “where the whole body is involved,” she said, adding that long-term doctor-patient relationships are “also attractive.”

Ms. Quintero is part of the Abigail Geisinger Scholars Program, which aims to recruit primary care physicians and psychiatrists to the rural health system in part with a promise of medical school loan forgiveness. Health care shortages tend to be more acute in rural areas.

These students’ education costs are covered, and they receive a $2,000 monthly stipend. They can do their residency elsewhere, but upon completing it they return to Geisinger for a primary care job with the health care system. Every year of work there erases one year of the debt covered by their award. If they don’t take a job with the health care system, they must repay the amount they received.
 

Payment imbalances a source of tension

In recent years, the Centers for Medicare & Medicaid Services, which administers the Medicare program, has made changes to address some of the payment imbalances between primary care and specialist services. The agency has expanded the office visit services for which providers can bill to manage their patients, including adding nonprocedural billing codes for providing transitional care, chronic care management, and advance care planning.

In 2024’s final physician fee schedule, the agency plans to allow another new code to take effect, G2211. It would let physicians bill for complex patient evaluation and management services. Any physician could use the code, but it is expected that primary care physicians would use it more frequently than specialists. Congress has delayed implementation of the code since 2021.

The new code is a tiny piece of overall payment reform, “but it is critically important, and it is our top priority on the Hill right now,” said Shari Erickson, chief advocacy officer for the American College of Physicians.

It also triggered a tussle that highlights ongoing tension in Medicare physician payment rules.

The American College of Surgeons and 18 other specialty groups published a statement describing the new code as “unnecessary.” They oppose its implementation because it would primarily benefit primary care providers who, they say, already have the flexibility to bill more for more complex visits.

But the real issue is that, under federal law, changes to Medicare physician payments must preserve budget neutrality, a zero-sum arrangement in which payment increases for primary care providers mean payment decreases elsewhere.

“If they want to keep it, they need to pay for it,” said Christian Shalgian, director of the division of advocacy and health policy for the American College of Surgeons, noting that his organization will continue to oppose implementation otherwise.

Still, there’s general agreement that strengthening the primary care system through payment reform won’t be accomplished by tinkering with billing codes.

The current fee-for-service system doesn’t fully accommodate the time and effort primary care physicians put into “small-ticket” activities like emails and phone calls, reviews of lab results, and consultation reports. A better arrangement, they say, would be to pay primary care physicians a set monthly amount per patient to provide all their care, a system called capitation.

“We’re much better off paying on a per capita basis, get that monthly payment paid in advance plus some extra amount for other things,” said Paul Ginsburg, PhD, a senior fellow at the University of Southern California Schaeffer Center for Health Policy and Economics and former commissioner of the Medicare Payment Advisory Commission.

But if adding a single five-character code to Medicare’s payment rules has proved challenging, imagine the heavy lift involved in overhauling the program’s entire physician payment system. MedPAC and the national academies, both of which provide advice to Congress, have weighed in on the broad outlines of what such a transformation might look like. And there are targeted efforts in Congress: For instance, a bill that would add an annual inflation update to Medicare physician payments and a proposal to address budget neutrality. But it’s unclear whether lawmakers have strong interest in taking action.

“The fact that Medicare has been squeezing physician payment rates for 2 decades is making reforming their structure more difficult,” said Dr. Ginsburg. “The losers are more sensitive to reductions in the rates for the procedures they do.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Money talks.

The United States faces a serious shortage of primary care physicians for many reasons, but one, in particular, is inescapable: compensation.

Substantial disparities between what primary care physicians earn relative to specialists like orthopedists and cardiologists can weigh into medical students’ decisions about which field to choose. Plus, the system that Medicare and other health plans use to pay doctors generally places more value on doing procedures like replacing a knee or inserting a stent than on delivering the whole-person, long-term health care management that primary care physicians provide.

As a result of those pay disparities, and the punishing workload typically faced by primary care physicians, more new doctors are becoming specialists, often leaving patients with fewer choices for primary care.

“There is a public out there that is dissatisfied with the lack of access to a routine source of care,” said Christopher Koller, president of the Milbank Memorial Fund, a foundation that focuses on improving population health and health equity. “That’s not going to be addressed until we pay for it.”

Primary care is the foundation of our health care system, the only area in which providing more services – such as childhood vaccines and regular blood pressure screenings – is linked to better population health and more equitable outcomes, according to the National Academies of Sciences, Engineering, and Medicine, in a recently published report on how to rebuild primary care. Without it, the national academies wrote, “minor health problems can spiral into chronic disease,” with poor disease management, ED overuse, and unsustainable costs. Yet for decades, the United States has underinvested in primary care. It accounted for less than 5% of health care spending in 2020 – significantly less than the average spending by countries that are members of the Organization for Economic Cooperation and Development, according to the report.

A $26 billion piece of bipartisan legislation proposed last month by Sen. Bernie Sanders (I-Vt.), chair of the Senate Health, Education, Labor, and Pensions Committee, and Sen. Roger Marshall (R-Kan.) would bolster primary care by increasing training opportunities for doctors and nurses and expanding access to community health centers. Policy experts say the bill would provide important support, but it’s not enough. It doesn’t touch compensation.

“We need primary care to be paid differently and to be paid more, and that starts with Medicare,” Mr. Koller said.
 

How Medicare drives payment

Medicare, which covers 65 million people who are 65 and older or who have certain long-term disabilities, finances more than a fifth of all health care spending — giving it significant muscle in the health care market. Private health plans typically base their payment amounts on the Medicare system, so what Medicare pays is crucial.

Under the Medicare payment system, the amount the program pays for a medical service is determined by three geographically weighted components: a physician’s work, including time and intensity; the practice’s expense, such as overhead and equipment; and professional insurance. It tends to reward specialties that emphasize procedures, such as repairing a hernia or removing a tumor, more than primary care, where the focus is on talking with patients, answering questions, and educating them about managing their chronic conditions.

Medical students may not be familiar with the particulars of how the payment system works, but their clinical training exposes them to a punishing workload and burnout that is contributing to the shortage of primary care physicians, projected to reach up to 48,000 by 2034, according to estimates from the Association of American Medical Colleges.

The earnings differential between primary care and other specialists is also not lost on them. Average annual compensation for doctors who focus on primary care – family medicine, internists, and pediatricians – ranges from an average of about $250,000 to $275,000, according to Medscape’s annual physician compensation report. Many specialists make more than twice as much: Plastic surgeons top the compensation list at $619,000 annually, followed by orthopedists ($573,000) and cardiologists ($507,000).

“I think the major issues in terms of the primary care physician pipeline are the compensation and the work of primary care,” said Russ Phillips, MD, an internist and the director of the Harvard Medical School Center for Primary Care, Boston. “You have to really want to be a primary care physician when that student will make one-third of what students going into dermatology will make.”

According to statistics from the National Resident Matching Program, which tracks the number of residency slots available for graduating medical students and the number of slots filled, 89% of 5,088 family medicine residency slots were filled in 2023, compared with a 93% residency fill rate overall. Internists had a higher fill rate, 96%, but a significant proportion of internal medicine residents eventually practice in a specialty area rather than in primary care.

No one would claim that doctors are poorly paid, but with the average medical student graduating with just over $200,000 in medical school debt, making a good salary matters.
 

Not in it for the money

Still, it’s a misperception that student debt always drives the decision whether to go into primary care, said Len Marquez, senior director of government relations and legislative advocacy at the Association of American Medical Colleges.

For Anitza Quintero, 24, a second-year medical student at the Geisinger Commonwealth School of Medicine in rural Pennsylvania, primary care is a logical extension of her interest in helping children and immigrants. Ms. Quintero’s family came to the United States on a raft from Cuba before she was born. She plans to focus on internal medicine and pediatrics.

“I want to keep going to help my family and other families,” Ms. Quintero said. “There’s obviously something attractive about having a specialty and a high pay grade,” Still, she wants to work “where the whole body is involved,” she said, adding that long-term doctor-patient relationships are “also attractive.”

Ms. Quintero is part of the Abigail Geisinger Scholars Program, which aims to recruit primary care physicians and psychiatrists to the rural health system in part with a promise of medical school loan forgiveness. Health care shortages tend to be more acute in rural areas.

These students’ education costs are covered, and they receive a $2,000 monthly stipend. They can do their residency elsewhere, but upon completing it they return to Geisinger for a primary care job with the health care system. Every year of work there erases one year of the debt covered by their award. If they don’t take a job with the health care system, they must repay the amount they received.
 

Payment imbalances a source of tension

In recent years, the Centers for Medicare & Medicaid Services, which administers the Medicare program, has made changes to address some of the payment imbalances between primary care and specialist services. The agency has expanded the office visit services for which providers can bill to manage their patients, including adding nonprocedural billing codes for providing transitional care, chronic care management, and advance care planning.

In 2024’s final physician fee schedule, the agency plans to allow another new code to take effect, G2211. It would let physicians bill for complex patient evaluation and management services. Any physician could use the code, but it is expected that primary care physicians would use it more frequently than specialists. Congress has delayed implementation of the code since 2021.

The new code is a tiny piece of overall payment reform, “but it is critically important, and it is our top priority on the Hill right now,” said Shari Erickson, chief advocacy officer for the American College of Physicians.

It also triggered a tussle that highlights ongoing tension in Medicare physician payment rules.

The American College of Surgeons and 18 other specialty groups published a statement describing the new code as “unnecessary.” They oppose its implementation because it would primarily benefit primary care providers who, they say, already have the flexibility to bill more for more complex visits.

But the real issue is that, under federal law, changes to Medicare physician payments must preserve budget neutrality, a zero-sum arrangement in which payment increases for primary care providers mean payment decreases elsewhere.

“If they want to keep it, they need to pay for it,” said Christian Shalgian, director of the division of advocacy and health policy for the American College of Surgeons, noting that his organization will continue to oppose implementation otherwise.

Still, there’s general agreement that strengthening the primary care system through payment reform won’t be accomplished by tinkering with billing codes.

The current fee-for-service system doesn’t fully accommodate the time and effort primary care physicians put into “small-ticket” activities like emails and phone calls, reviews of lab results, and consultation reports. A better arrangement, they say, would be to pay primary care physicians a set monthly amount per patient to provide all their care, a system called capitation.

“We’re much better off paying on a per capita basis, get that monthly payment paid in advance plus some extra amount for other things,” said Paul Ginsburg, PhD, a senior fellow at the University of Southern California Schaeffer Center for Health Policy and Economics and former commissioner of the Medicare Payment Advisory Commission.

But if adding a single five-character code to Medicare’s payment rules has proved challenging, imagine the heavy lift involved in overhauling the program’s entire physician payment system. MedPAC and the national academies, both of which provide advice to Congress, have weighed in on the broad outlines of what such a transformation might look like. And there are targeted efforts in Congress: For instance, a bill that would add an annual inflation update to Medicare physician payments and a proposal to address budget neutrality. But it’s unclear whether lawmakers have strong interest in taking action.

“The fact that Medicare has been squeezing physician payment rates for 2 decades is making reforming their structure more difficult,” said Dr. Ginsburg. “The losers are more sensitive to reductions in the rates for the procedures they do.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Money talks.

The United States faces a serious shortage of primary care physicians for many reasons, but one, in particular, is inescapable: compensation.

Substantial disparities between what primary care physicians earn relative to specialists like orthopedists and cardiologists can weigh into medical students’ decisions about which field to choose. Plus, the system that Medicare and other health plans use to pay doctors generally places more value on doing procedures like replacing a knee or inserting a stent than on delivering the whole-person, long-term health care management that primary care physicians provide.

As a result of those pay disparities, and the punishing workload typically faced by primary care physicians, more new doctors are becoming specialists, often leaving patients with fewer choices for primary care.

“There is a public out there that is dissatisfied with the lack of access to a routine source of care,” said Christopher Koller, president of the Milbank Memorial Fund, a foundation that focuses on improving population health and health equity. “That’s not going to be addressed until we pay for it.”

Primary care is the foundation of our health care system, the only area in which providing more services – such as childhood vaccines and regular blood pressure screenings – is linked to better population health and more equitable outcomes, according to the National Academies of Sciences, Engineering, and Medicine, in a recently published report on how to rebuild primary care. Without it, the national academies wrote, “minor health problems can spiral into chronic disease,” with poor disease management, ED overuse, and unsustainable costs. Yet for decades, the United States has underinvested in primary care. It accounted for less than 5% of health care spending in 2020 – significantly less than the average spending by countries that are members of the Organization for Economic Cooperation and Development, according to the report.

A $26 billion piece of bipartisan legislation proposed last month by Sen. Bernie Sanders (I-Vt.), chair of the Senate Health, Education, Labor, and Pensions Committee, and Sen. Roger Marshall (R-Kan.) would bolster primary care by increasing training opportunities for doctors and nurses and expanding access to community health centers. Policy experts say the bill would provide important support, but it’s not enough. It doesn’t touch compensation.

“We need primary care to be paid differently and to be paid more, and that starts with Medicare,” Mr. Koller said.
 

How Medicare drives payment

Medicare, which covers 65 million people who are 65 and older or who have certain long-term disabilities, finances more than a fifth of all health care spending — giving it significant muscle in the health care market. Private health plans typically base their payment amounts on the Medicare system, so what Medicare pays is crucial.

Under the Medicare payment system, the amount the program pays for a medical service is determined by three geographically weighted components: a physician’s work, including time and intensity; the practice’s expense, such as overhead and equipment; and professional insurance. It tends to reward specialties that emphasize procedures, such as repairing a hernia or removing a tumor, more than primary care, where the focus is on talking with patients, answering questions, and educating them about managing their chronic conditions.

Medical students may not be familiar with the particulars of how the payment system works, but their clinical training exposes them to a punishing workload and burnout that is contributing to the shortage of primary care physicians, projected to reach up to 48,000 by 2034, according to estimates from the Association of American Medical Colleges.

The earnings differential between primary care and other specialists is also not lost on them. Average annual compensation for doctors who focus on primary care – family medicine, internists, and pediatricians – ranges from an average of about $250,000 to $275,000, according to Medscape’s annual physician compensation report. Many specialists make more than twice as much: Plastic surgeons top the compensation list at $619,000 annually, followed by orthopedists ($573,000) and cardiologists ($507,000).

“I think the major issues in terms of the primary care physician pipeline are the compensation and the work of primary care,” said Russ Phillips, MD, an internist and the director of the Harvard Medical School Center for Primary Care, Boston. “You have to really want to be a primary care physician when that student will make one-third of what students going into dermatology will make.”

According to statistics from the National Resident Matching Program, which tracks the number of residency slots available for graduating medical students and the number of slots filled, 89% of 5,088 family medicine residency slots were filled in 2023, compared with a 93% residency fill rate overall. Internists had a higher fill rate, 96%, but a significant proportion of internal medicine residents eventually practice in a specialty area rather than in primary care.

No one would claim that doctors are poorly paid, but with the average medical student graduating with just over $200,000 in medical school debt, making a good salary matters.
 

Not in it for the money

Still, it’s a misperception that student debt always drives the decision whether to go into primary care, said Len Marquez, senior director of government relations and legislative advocacy at the Association of American Medical Colleges.

For Anitza Quintero, 24, a second-year medical student at the Geisinger Commonwealth School of Medicine in rural Pennsylvania, primary care is a logical extension of her interest in helping children and immigrants. Ms. Quintero’s family came to the United States on a raft from Cuba before she was born. She plans to focus on internal medicine and pediatrics.

“I want to keep going to help my family and other families,” Ms. Quintero said. “There’s obviously something attractive about having a specialty and a high pay grade,” Still, she wants to work “where the whole body is involved,” she said, adding that long-term doctor-patient relationships are “also attractive.”

Ms. Quintero is part of the Abigail Geisinger Scholars Program, which aims to recruit primary care physicians and psychiatrists to the rural health system in part with a promise of medical school loan forgiveness. Health care shortages tend to be more acute in rural areas.

These students’ education costs are covered, and they receive a $2,000 monthly stipend. They can do their residency elsewhere, but upon completing it they return to Geisinger for a primary care job with the health care system. Every year of work there erases one year of the debt covered by their award. If they don’t take a job with the health care system, they must repay the amount they received.
 

Payment imbalances a source of tension

In recent years, the Centers for Medicare & Medicaid Services, which administers the Medicare program, has made changes to address some of the payment imbalances between primary care and specialist services. The agency has expanded the office visit services for which providers can bill to manage their patients, including adding nonprocedural billing codes for providing transitional care, chronic care management, and advance care planning.

In 2024’s final physician fee schedule, the agency plans to allow another new code to take effect, G2211. It would let physicians bill for complex patient evaluation and management services. Any physician could use the code, but it is expected that primary care physicians would use it more frequently than specialists. Congress has delayed implementation of the code since 2021.

The new code is a tiny piece of overall payment reform, “but it is critically important, and it is our top priority on the Hill right now,” said Shari Erickson, chief advocacy officer for the American College of Physicians.

It also triggered a tussle that highlights ongoing tension in Medicare physician payment rules.

The American College of Surgeons and 18 other specialty groups published a statement describing the new code as “unnecessary.” They oppose its implementation because it would primarily benefit primary care providers who, they say, already have the flexibility to bill more for more complex visits.

But the real issue is that, under federal law, changes to Medicare physician payments must preserve budget neutrality, a zero-sum arrangement in which payment increases for primary care providers mean payment decreases elsewhere.

“If they want to keep it, they need to pay for it,” said Christian Shalgian, director of the division of advocacy and health policy for the American College of Surgeons, noting that his organization will continue to oppose implementation otherwise.

Still, there’s general agreement that strengthening the primary care system through payment reform won’t be accomplished by tinkering with billing codes.

The current fee-for-service system doesn’t fully accommodate the time and effort primary care physicians put into “small-ticket” activities like emails and phone calls, reviews of lab results, and consultation reports. A better arrangement, they say, would be to pay primary care physicians a set monthly amount per patient to provide all their care, a system called capitation.

“We’re much better off paying on a per capita basis, get that monthly payment paid in advance plus some extra amount for other things,” said Paul Ginsburg, PhD, a senior fellow at the University of Southern California Schaeffer Center for Health Policy and Economics and former commissioner of the Medicare Payment Advisory Commission.

But if adding a single five-character code to Medicare’s payment rules has proved challenging, imagine the heavy lift involved in overhauling the program’s entire physician payment system. MedPAC and the national academies, both of which provide advice to Congress, have weighed in on the broad outlines of what such a transformation might look like. And there are targeted efforts in Congress: For instance, a bill that would add an annual inflation update to Medicare physician payments and a proposal to address budget neutrality. But it’s unclear whether lawmakers have strong interest in taking action.

“The fact that Medicare has been squeezing physician payment rates for 2 decades is making reforming their structure more difficult,” said Dr. Ginsburg. “The losers are more sensitive to reductions in the rates for the procedures they do.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

WASHINGTON – Black children had 2.5 greater odds than White children of dying from sepsis in the hospital, despite no significantly different rates of clinical interventions, according to research presented at the annual meeting of the American Academy of Pediatrics.

The only other difference between Black and White pediatric patients was the length of hospital stay and the length of time in the ICU among those who died. In both cases, Black children who died spent more time in the hospital and in the ICU, reported Michael H. Stroud, MD, a pediatric critical care physician at the University of Arkansas for Medical Sciences in Little Rock, and his colleagues.

“Further investigations are needed to identify biases, conscious and unconscious, potential socioeconomic factors, and genetic predispositions leading to racial disparities in outcomes of children with pediatric sepsis, severe sepsis, and septic shock,” Dr Stroud and his colleagues said.

Nathan T. Chomilo, MD, adjunct assistant professor of pediatrics at the University of Minnesota, Minneapolis, who was not involved in the study but reviewed it, said the research “builds upon existing evidence that our health care system has work to do to meet its goal of treating patients equitably and provide everyone the opportunity for health.” He found the racial disparity in death particularly striking in 2023. “In the U.S., with all our wealth, knowledge, and resources, very few children should die from this, let alone there be such a stark gap,” Dr. Chomilo wrote.
 

Racial disparities persist

Dr. Stroud noted that many institutions currently use “automated, real-time, algorithm-based detection of sepsis, severe sepsis, and septic shock incorporated into the electronic medical record,” which leads to earlier recognition and resuscitation and overall better outcomes. Yet racial disparities in sepsis mortality rates persist, and he and his colleagues wanted to explore whether they remained even with these EMR-incorporated systems.

The researchers analyzed data from all patients at Arkansas Children’s Hospital who had sepsis, severe sepsis, or septic shock between January 2018 and April 2022. The hospital uses a best practice advisory (BPA) in the EMR whose activation leads to a bedside huddle and clinical interventions. For this study, the researchers defined a sepsis episode as either a BPA activation or an EMR diagnosis of sepsis, severe sepsis, or septic shock.

Among the 3,514 patients who had a sepsis episode during the study, 60.5% were White (n = 2,126) and 20.9% were Black (n = 736). Overall mortality was 1.65%, but that included 3.13% of Black children versus 1.27% of White children (odds ratio [OR] 2.51, P = .001). No significant differences in mortality were seen in gender or age.

Clinical interventions in the two groups were also similar: Total IV antibiotic days were 23.8 days for Black children and 21.6 days for White children (P = .38); total vasoactive infusion days were 2.2 for Black children and 2.6 for White (P = .18); and extracorporeal membrane oxygenation was necessary for 26.1% of Black children and 18.5% of White children (P = .52).

Length of hospitalization stay, however, was an average 4 days longer for Black children (16.7 days) versus White children (12.7 days) who died (P = .03). ICU stay for Black children who died was also an average 1.9 days longer (7.57 vs. 5.7 days; P = .01). There were no significant differences in the EMR between Black and White patients, however, in the percent who were over the threshold for antibiotic administration and the percent who received an IV fluid bolus.
 

Contributing factors

Dr. Chomilo said that most BPA systems require staff – including rooming and triage staff, nurses. and physicians – to enter vital signs, order labs, enter the results into the system, and enter other data used by the algorithm. “So even though the time from when those BPA warnings flagged to when clinical interventions were documented didn’t show a significant difference, there are numerous other points along a child’s illness that may be contributing to these numbers,” Dr. Chomilo said.

For example, he pointed out that differences in health insurance coverage could have influenced whether their parent or caregiver was able to bring them in early enough to be diagnosed since studies have revealed disparate access to regular care due to structural racism in the health care system. Studies have also shown disparate rates of patients being triaged or having to wait longer in emergency departments, he added.

“When the child was brought in, how were they triaged? How long did they wait before they had vitals taken? How long until they were seen by a clinician?” Dr. Chomilo said. “Was their care on the inpatient ward the same or different? What was the source of sepsis? Was it all infectious or other issues [since] cancer and autoimmune illnesses can also trigger a sepsis evaluation, for example? Overall, I suspect answers to several of these questions would reveal a disparity due to structural racism that contributed to the ultimate disparity in deaths.”

Other social determinants of health that could have played a role in the outcome disparities here might include the family’s access to transportation options, parental employment or child care options, and nutrition access since baseline nutritional status can be a factor in the outcomes of severe illnesses like sepsis.

”I don’t think this study provided enough information about the potential causative factors to come to any strong conclusions,” Dr. Chomilo said. But it’s important for clinicians to be aware of how biases in the health care system put Black, Indigenous and other communities at higher risk for worse clinical outcomes.

“I would reiterate that clinicians in the hospital can help improve outcomes by being aware of structural racism and structural inequity and how that may contribute to their patient’s risk of severe illness as the decide how to approach their treatment and engaging the patient’s family,” Dr. Chomilo said. “We cannot rely solely on universal tools that don’t take this into account when we are looking to improve clinical outcomes for everyone. Otherwise we will see these gaps persist.”

No external funding sources were noted. Dr. Stroud and Dr. Chomilo had no disclosures.

WASHINGTON – Black children had 2.5 greater odds than White children of dying from sepsis in the hospital, despite no significantly different rates of clinical interventions, according to research presented at the annual meeting of the American Academy of Pediatrics.

The only other difference between Black and White pediatric patients was the length of hospital stay and the length of time in the ICU among those who died. In both cases, Black children who died spent more time in the hospital and in the ICU, reported Michael H. Stroud, MD, a pediatric critical care physician at the University of Arkansas for Medical Sciences in Little Rock, and his colleagues.

“Further investigations are needed to identify biases, conscious and unconscious, potential socioeconomic factors, and genetic predispositions leading to racial disparities in outcomes of children with pediatric sepsis, severe sepsis, and septic shock,” Dr Stroud and his colleagues said.

Nathan T. Chomilo, MD, adjunct assistant professor of pediatrics at the University of Minnesota, Minneapolis, who was not involved in the study but reviewed it, said the research “builds upon existing evidence that our health care system has work to do to meet its goal of treating patients equitably and provide everyone the opportunity for health.” He found the racial disparity in death particularly striking in 2023. “In the U.S., with all our wealth, knowledge, and resources, very few children should die from this, let alone there be such a stark gap,” Dr. Chomilo wrote.
 

Racial disparities persist

Dr. Stroud noted that many institutions currently use “automated, real-time, algorithm-based detection of sepsis, severe sepsis, and septic shock incorporated into the electronic medical record,” which leads to earlier recognition and resuscitation and overall better outcomes. Yet racial disparities in sepsis mortality rates persist, and he and his colleagues wanted to explore whether they remained even with these EMR-incorporated systems.

The researchers analyzed data from all patients at Arkansas Children’s Hospital who had sepsis, severe sepsis, or septic shock between January 2018 and April 2022. The hospital uses a best practice advisory (BPA) in the EMR whose activation leads to a bedside huddle and clinical interventions. For this study, the researchers defined a sepsis episode as either a BPA activation or an EMR diagnosis of sepsis, severe sepsis, or septic shock.

Among the 3,514 patients who had a sepsis episode during the study, 60.5% were White (n = 2,126) and 20.9% were Black (n = 736). Overall mortality was 1.65%, but that included 3.13% of Black children versus 1.27% of White children (odds ratio [OR] 2.51, P = .001). No significant differences in mortality were seen in gender or age.

Clinical interventions in the two groups were also similar: Total IV antibiotic days were 23.8 days for Black children and 21.6 days for White children (P = .38); total vasoactive infusion days were 2.2 for Black children and 2.6 for White (P = .18); and extracorporeal membrane oxygenation was necessary for 26.1% of Black children and 18.5% of White children (P = .52).

Length of hospitalization stay, however, was an average 4 days longer for Black children (16.7 days) versus White children (12.7 days) who died (P = .03). ICU stay for Black children who died was also an average 1.9 days longer (7.57 vs. 5.7 days; P = .01). There were no significant differences in the EMR between Black and White patients, however, in the percent who were over the threshold for antibiotic administration and the percent who received an IV fluid bolus.
 

Contributing factors

Dr. Chomilo said that most BPA systems require staff – including rooming and triage staff, nurses. and physicians – to enter vital signs, order labs, enter the results into the system, and enter other data used by the algorithm. “So even though the time from when those BPA warnings flagged to when clinical interventions were documented didn’t show a significant difference, there are numerous other points along a child’s illness that may be contributing to these numbers,” Dr. Chomilo said.

For example, he pointed out that differences in health insurance coverage could have influenced whether their parent or caregiver was able to bring them in early enough to be diagnosed since studies have revealed disparate access to regular care due to structural racism in the health care system. Studies have also shown disparate rates of patients being triaged or having to wait longer in emergency departments, he added.

“When the child was brought in, how were they triaged? How long did they wait before they had vitals taken? How long until they were seen by a clinician?” Dr. Chomilo said. “Was their care on the inpatient ward the same or different? What was the source of sepsis? Was it all infectious or other issues [since] cancer and autoimmune illnesses can also trigger a sepsis evaluation, for example? Overall, I suspect answers to several of these questions would reveal a disparity due to structural racism that contributed to the ultimate disparity in deaths.”

Other social determinants of health that could have played a role in the outcome disparities here might include the family’s access to transportation options, parental employment or child care options, and nutrition access since baseline nutritional status can be a factor in the outcomes of severe illnesses like sepsis.

”I don’t think this study provided enough information about the potential causative factors to come to any strong conclusions,” Dr. Chomilo said. But it’s important for clinicians to be aware of how biases in the health care system put Black, Indigenous and other communities at higher risk for worse clinical outcomes.

“I would reiterate that clinicians in the hospital can help improve outcomes by being aware of structural racism and structural inequity and how that may contribute to their patient’s risk of severe illness as the decide how to approach their treatment and engaging the patient’s family,” Dr. Chomilo said. “We cannot rely solely on universal tools that don’t take this into account when we are looking to improve clinical outcomes for everyone. Otherwise we will see these gaps persist.”

No external funding sources were noted. Dr. Stroud and Dr. Chomilo had no disclosures.

WASHINGTON – Black children had 2.5 greater odds than White children of dying from sepsis in the hospital, despite no significantly different rates of clinical interventions, according to research presented at the annual meeting of the American Academy of Pediatrics.

The only other difference between Black and White pediatric patients was the length of hospital stay and the length of time in the ICU among those who died. In both cases, Black children who died spent more time in the hospital and in the ICU, reported Michael H. Stroud, MD, a pediatric critical care physician at the University of Arkansas for Medical Sciences in Little Rock, and his colleagues.

“Further investigations are needed to identify biases, conscious and unconscious, potential socioeconomic factors, and genetic predispositions leading to racial disparities in outcomes of children with pediatric sepsis, severe sepsis, and septic shock,” Dr Stroud and his colleagues said.

Nathan T. Chomilo, MD, adjunct assistant professor of pediatrics at the University of Minnesota, Minneapolis, who was not involved in the study but reviewed it, said the research “builds upon existing evidence that our health care system has work to do to meet its goal of treating patients equitably and provide everyone the opportunity for health.” He found the racial disparity in death particularly striking in 2023. “In the U.S., with all our wealth, knowledge, and resources, very few children should die from this, let alone there be such a stark gap,” Dr. Chomilo wrote.
 

Racial disparities persist

Dr. Stroud noted that many institutions currently use “automated, real-time, algorithm-based detection of sepsis, severe sepsis, and septic shock incorporated into the electronic medical record,” which leads to earlier recognition and resuscitation and overall better outcomes. Yet racial disparities in sepsis mortality rates persist, and he and his colleagues wanted to explore whether they remained even with these EMR-incorporated systems.

The researchers analyzed data from all patients at Arkansas Children’s Hospital who had sepsis, severe sepsis, or septic shock between January 2018 and April 2022. The hospital uses a best practice advisory (BPA) in the EMR whose activation leads to a bedside huddle and clinical interventions. For this study, the researchers defined a sepsis episode as either a BPA activation or an EMR diagnosis of sepsis, severe sepsis, or septic shock.

Among the 3,514 patients who had a sepsis episode during the study, 60.5% were White (n = 2,126) and 20.9% were Black (n = 736). Overall mortality was 1.65%, but that included 3.13% of Black children versus 1.27% of White children (odds ratio [OR] 2.51, P = .001). No significant differences in mortality were seen in gender or age.

Clinical interventions in the two groups were also similar: Total IV antibiotic days were 23.8 days for Black children and 21.6 days for White children (P = .38); total vasoactive infusion days were 2.2 for Black children and 2.6 for White (P = .18); and extracorporeal membrane oxygenation was necessary for 26.1% of Black children and 18.5% of White children (P = .52).

Length of hospitalization stay, however, was an average 4 days longer for Black children (16.7 days) versus White children (12.7 days) who died (P = .03). ICU stay for Black children who died was also an average 1.9 days longer (7.57 vs. 5.7 days; P = .01). There were no significant differences in the EMR between Black and White patients, however, in the percent who were over the threshold for antibiotic administration and the percent who received an IV fluid bolus.
 

Contributing factors

Dr. Chomilo said that most BPA systems require staff – including rooming and triage staff, nurses. and physicians – to enter vital signs, order labs, enter the results into the system, and enter other data used by the algorithm. “So even though the time from when those BPA warnings flagged to when clinical interventions were documented didn’t show a significant difference, there are numerous other points along a child’s illness that may be contributing to these numbers,” Dr. Chomilo said.

For example, he pointed out that differences in health insurance coverage could have influenced whether their parent or caregiver was able to bring them in early enough to be diagnosed since studies have revealed disparate access to regular care due to structural racism in the health care system. Studies have also shown disparate rates of patients being triaged or having to wait longer in emergency departments, he added.

“When the child was brought in, how were they triaged? How long did they wait before they had vitals taken? How long until they were seen by a clinician?” Dr. Chomilo said. “Was their care on the inpatient ward the same or different? What was the source of sepsis? Was it all infectious or other issues [since] cancer and autoimmune illnesses can also trigger a sepsis evaluation, for example? Overall, I suspect answers to several of these questions would reveal a disparity due to structural racism that contributed to the ultimate disparity in deaths.”

Other social determinants of health that could have played a role in the outcome disparities here might include the family’s access to transportation options, parental employment or child care options, and nutrition access since baseline nutritional status can be a factor in the outcomes of severe illnesses like sepsis.

”I don’t think this study provided enough information about the potential causative factors to come to any strong conclusions,” Dr. Chomilo said. But it’s important for clinicians to be aware of how biases in the health care system put Black, Indigenous and other communities at higher risk for worse clinical outcomes.

“I would reiterate that clinicians in the hospital can help improve outcomes by being aware of structural racism and structural inequity and how that may contribute to their patient’s risk of severe illness as the decide how to approach their treatment and engaging the patient’s family,” Dr. Chomilo said. “We cannot rely solely on universal tools that don’t take this into account when we are looking to improve clinical outcomes for everyone. Otherwise we will see these gaps persist.”

No external funding sources were noted. Dr. Stroud and Dr. Chomilo had no disclosures.

People who want to be tested for chlamydia and gonorrhea are now able to do so without leaving their homes.

Called Simple 2, it’s the first test approved by the Food and Drug Administration that uses a sample collected at home to test for an STD, other than tests for HIV. The test can be purchased over-the-counter in stores or ordered online and delivered in discreet packaging. A vaginal swab or urine sample is collected and then sent for laboratory testing using a prepaid shipping label.

The FDA issued the final needed approval on Nov. 15, and the product is already for sale on the website of the manufacturer, LetsGetChecked. The listed price is $99 with free shipping for a single test kit, and the site offers a discounted subscription to receive a kit every 3 months for $69.30 per kit.

Gonorrhea cases have surged 28% since 2017, reaching 700,000 cases during 2021, Centers for Disease Control and Prevention data show. Chlamydia has also been on the rise, up 4% from 2020 to 2021, with 1.6 million annual infections.

Previously, tests for the two STDs required that samples be taken at a health care location such as a doctor’s office. The Simple 2 test results can be retrieved online, and a health care provider will reach out to people whose tests are positive or invalid. Results are typically received in 2-5 days, according to a press release from LetsGetChecked, which also offers treatment services.

“This authorization marks an important public health milestone, giving patients more information about their health from the privacy of their own home,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a statement. “We are eager to continue supporting greater consumer access to diagnostic tests, which helps further our goal of bringing more health care into the home.”

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

People who want to be tested for chlamydia and gonorrhea are now able to do so without leaving their homes.

Called Simple 2, it’s the first test approved by the Food and Drug Administration that uses a sample collected at home to test for an STD, other than tests for HIV. The test can be purchased over-the-counter in stores or ordered online and delivered in discreet packaging. A vaginal swab or urine sample is collected and then sent for laboratory testing using a prepaid shipping label.

The FDA issued the final needed approval on Nov. 15, and the product is already for sale on the website of the manufacturer, LetsGetChecked. The listed price is $99 with free shipping for a single test kit, and the site offers a discounted subscription to receive a kit every 3 months for $69.30 per kit.

Gonorrhea cases have surged 28% since 2017, reaching 700,000 cases during 2021, Centers for Disease Control and Prevention data show. Chlamydia has also been on the rise, up 4% from 2020 to 2021, with 1.6 million annual infections.

Previously, tests for the two STDs required that samples be taken at a health care location such as a doctor’s office. The Simple 2 test results can be retrieved online, and a health care provider will reach out to people whose tests are positive or invalid. Results are typically received in 2-5 days, according to a press release from LetsGetChecked, which also offers treatment services.

“This authorization marks an important public health milestone, giving patients more information about their health from the privacy of their own home,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a statement. “We are eager to continue supporting greater consumer access to diagnostic tests, which helps further our goal of bringing more health care into the home.”

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

People who want to be tested for chlamydia and gonorrhea are now able to do so without leaving their homes.

Called Simple 2, it’s the first test approved by the Food and Drug Administration that uses a sample collected at home to test for an STD, other than tests for HIV. The test can be purchased over-the-counter in stores or ordered online and delivered in discreet packaging. A vaginal swab or urine sample is collected and then sent for laboratory testing using a prepaid shipping label.

The FDA issued the final needed approval on Nov. 15, and the product is already for sale on the website of the manufacturer, LetsGetChecked. The listed price is $99 with free shipping for a single test kit, and the site offers a discounted subscription to receive a kit every 3 months for $69.30 per kit.

Gonorrhea cases have surged 28% since 2017, reaching 700,000 cases during 2021, Centers for Disease Control and Prevention data show. Chlamydia has also been on the rise, up 4% from 2020 to 2021, with 1.6 million annual infections.

Previously, tests for the two STDs required that samples be taken at a health care location such as a doctor’s office. The Simple 2 test results can be retrieved online, and a health care provider will reach out to people whose tests are positive or invalid. Results are typically received in 2-5 days, according to a press release from LetsGetChecked, which also offers treatment services.

“This authorization marks an important public health milestone, giving patients more information about their health from the privacy of their own home,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a statement. “We are eager to continue supporting greater consumer access to diagnostic tests, which helps further our goal of bringing more health care into the home.”

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

More children and preteens are taking melatonin to help them sleep, a new study found, while experts cautioned parents may be unaware of some risks, particularly with long-term use. 

The investigators noted not all melatonin supplements contain what they say they do – some tested in a separate study contained two to three times the amount of melatonin on the label, and one supplement contained none at all.
 

A matter of timing?

While not completely advising against the sleep supplement, the study researchers pointed out that short-term use is likely safer. 

“We are not saying that melatonin is necessarily harmful to children. But much more research needs to be done before we can state with confidence that it is safe for kids to be taking long term,” lead study author Lauren Hartstein, PhD, a postdoctoral fellow in the Sleep and Development Lab at the University of Colorado in Boulder, said in a news release.

“If, after weighing potential risks and benefits, melatonin is recommended as the appropriate treatment, [a sleep medicine specialist] can recommend a dose and timing to treat the sleep issue,” said Raj Bhui, MD, a sleep medicine specialist and American Academy of Sleep Medicine spokesperson, who was not involved in the study.
 

An increasing trend

From 2017 to 2018, only about 1.3% of parents reported their children used melatonin in national data looking at supplement use in children and teenagers. In fact, usage more than doubled in this younger population from 2017 to 2020, another study revealed. “All of a sudden, in 2022, we started noticing a lot of parents telling us that their healthy child was regularly taking melatonin,” Dr. Hartstein said.

She and colleagues surveyed the parents of 993 children, aged 1 to less than 14, from January to April 2023. They found about 20% of these school-aged children and preteens took melatonin as a sleep aid. The findings, published in the journal JAMA Pediatrics, also suggest that some parents routinely give their preschool children melatonin.

They found nearly 6% of preschoolers aged 1-4, 18.5% of children aged 5-9, and 19.4% of kids aged 10-13 had taken melatonin in the previous month. 

The researchers also discovered that many took melatonin for longer than a few nights. Preschool children took the supplement for a median of 1 year, grade school children for a median 18 months, and preteens for 21 months. 
 

What’s in your supplement? 

In a different study published April 25 (JAMA. 2023. doi: 10.1001/jama.2023.2296), researchers looked at 25 melatonin gummy products and found that 22 of them contained different amounts of melatonin than listed on the label. In fact, one called Sleep Plus Immune contained more than three times the amount, and with a supplement called Sleep Support, researchers could not detect any melatonin. 

There is a general misconception that supplements are natural and therefore safe, Dr. Bhui said. “Multiple investigations of commercially available supplements have shown we cannot assume that what is on the label is in the pill or that what is in the pill is disclosed on the label. Formal laboratory testing has revealed some supplements to be adulterated with unapproved pharmaceutical ingredients, contaminated with microbes, or even tainted with toxins like arsenic, lead, and mercury.”

Choosing a product with the “USP Verified Mark” may give parents some comfort regarding melatonin content and consistency with labeling, Dr. Bhui said. Taking steps to safeguard the supply at home is also important in making sure children don’t take the supplements by accident. “With the increased use of melatonin, this has been a growing problem.”

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

More children and preteens are taking melatonin to help them sleep, a new study found, while experts cautioned parents may be unaware of some risks, particularly with long-term use. 

The investigators noted not all melatonin supplements contain what they say they do – some tested in a separate study contained two to three times the amount of melatonin on the label, and one supplement contained none at all.
 

A matter of timing?

While not completely advising against the sleep supplement, the study researchers pointed out that short-term use is likely safer. 

“We are not saying that melatonin is necessarily harmful to children. But much more research needs to be done before we can state with confidence that it is safe for kids to be taking long term,” lead study author Lauren Hartstein, PhD, a postdoctoral fellow in the Sleep and Development Lab at the University of Colorado in Boulder, said in a news release.

“If, after weighing potential risks and benefits, melatonin is recommended as the appropriate treatment, [a sleep medicine specialist] can recommend a dose and timing to treat the sleep issue,” said Raj Bhui, MD, a sleep medicine specialist and American Academy of Sleep Medicine spokesperson, who was not involved in the study.
 

An increasing trend

From 2017 to 2018, only about 1.3% of parents reported their children used melatonin in national data looking at supplement use in children and teenagers. In fact, usage more than doubled in this younger population from 2017 to 2020, another study revealed. “All of a sudden, in 2022, we started noticing a lot of parents telling us that their healthy child was regularly taking melatonin,” Dr. Hartstein said.

She and colleagues surveyed the parents of 993 children, aged 1 to less than 14, from January to April 2023. They found about 20% of these school-aged children and preteens took melatonin as a sleep aid. The findings, published in the journal JAMA Pediatrics, also suggest that some parents routinely give their preschool children melatonin.

They found nearly 6% of preschoolers aged 1-4, 18.5% of children aged 5-9, and 19.4% of kids aged 10-13 had taken melatonin in the previous month. 

The researchers also discovered that many took melatonin for longer than a few nights. Preschool children took the supplement for a median of 1 year, grade school children for a median 18 months, and preteens for 21 months. 
 

What’s in your supplement? 

In a different study published April 25 (JAMA. 2023. doi: 10.1001/jama.2023.2296), researchers looked at 25 melatonin gummy products and found that 22 of them contained different amounts of melatonin than listed on the label. In fact, one called Sleep Plus Immune contained more than three times the amount, and with a supplement called Sleep Support, researchers could not detect any melatonin. 

There is a general misconception that supplements are natural and therefore safe, Dr. Bhui said. “Multiple investigations of commercially available supplements have shown we cannot assume that what is on the label is in the pill or that what is in the pill is disclosed on the label. Formal laboratory testing has revealed some supplements to be adulterated with unapproved pharmaceutical ingredients, contaminated with microbes, or even tainted with toxins like arsenic, lead, and mercury.”

Choosing a product with the “USP Verified Mark” may give parents some comfort regarding melatonin content and consistency with labeling, Dr. Bhui said. Taking steps to safeguard the supply at home is also important in making sure children don’t take the supplements by accident. “With the increased use of melatonin, this has been a growing problem.”

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

More children and preteens are taking melatonin to help them sleep, a new study found, while experts cautioned parents may be unaware of some risks, particularly with long-term use. 

The investigators noted not all melatonin supplements contain what they say they do – some tested in a separate study contained two to three times the amount of melatonin on the label, and one supplement contained none at all.
 

A matter of timing?

While not completely advising against the sleep supplement, the study researchers pointed out that short-term use is likely safer. 

“We are not saying that melatonin is necessarily harmful to children. But much more research needs to be done before we can state with confidence that it is safe for kids to be taking long term,” lead study author Lauren Hartstein, PhD, a postdoctoral fellow in the Sleep and Development Lab at the University of Colorado in Boulder, said in a news release.

“If, after weighing potential risks and benefits, melatonin is recommended as the appropriate treatment, [a sleep medicine specialist] can recommend a dose and timing to treat the sleep issue,” said Raj Bhui, MD, a sleep medicine specialist and American Academy of Sleep Medicine spokesperson, who was not involved in the study.
 

An increasing trend

From 2017 to 2018, only about 1.3% of parents reported their children used melatonin in national data looking at supplement use in children and teenagers. In fact, usage more than doubled in this younger population from 2017 to 2020, another study revealed. “All of a sudden, in 2022, we started noticing a lot of parents telling us that their healthy child was regularly taking melatonin,” Dr. Hartstein said.

She and colleagues surveyed the parents of 993 children, aged 1 to less than 14, from January to April 2023. They found about 20% of these school-aged children and preteens took melatonin as a sleep aid. The findings, published in the journal JAMA Pediatrics, also suggest that some parents routinely give their preschool children melatonin.

They found nearly 6% of preschoolers aged 1-4, 18.5% of children aged 5-9, and 19.4% of kids aged 10-13 had taken melatonin in the previous month. 

The researchers also discovered that many took melatonin for longer than a few nights. Preschool children took the supplement for a median of 1 year, grade school children for a median 18 months, and preteens for 21 months. 
 

What’s in your supplement? 

In a different study published April 25 (JAMA. 2023. doi: 10.1001/jama.2023.2296), researchers looked at 25 melatonin gummy products and found that 22 of them contained different amounts of melatonin than listed on the label. In fact, one called Sleep Plus Immune contained more than three times the amount, and with a supplement called Sleep Support, researchers could not detect any melatonin. 

There is a general misconception that supplements are natural and therefore safe, Dr. Bhui said. “Multiple investigations of commercially available supplements have shown we cannot assume that what is on the label is in the pill or that what is in the pill is disclosed on the label. Formal laboratory testing has revealed some supplements to be adulterated with unapproved pharmaceutical ingredients, contaminated with microbes, or even tainted with toxins like arsenic, lead, and mercury.”

Choosing a product with the “USP Verified Mark” may give parents some comfort regarding melatonin content and consistency with labeling, Dr. Bhui said. Taking steps to safeguard the supply at home is also important in making sure children don’t take the supplements by accident. “With the increased use of melatonin, this has been a growing problem.”

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

An anesthesiologist is suing the Mayo Clinic after it allegedly ordered him to stick to “prescribed messaging” after his outspoken comments about transgender athletes and a federal agency’s sluggishness regarding a COVID-19 treatment.

Michael J. Joyner, MD, claims that the Mayo Clinic violated its own policies by muzzling him, slapping him with an unpaid 1-week suspension, and labeling his comments to the media “unprofessional.”

In his Nov. 13 lawsuit, filed in Minnesota state court, Dr. Joyner asks that a judge order Mayo Clinic to stop its “retaliation and interference” with his “communications about his research.” He that claims the retaliation stems from his 2020 report about a Mayo Clinic business partner’s “attempt to unlawfully access and use protected patient data.”

Medical institutions often refuse to comment on pending litigation. But in a pair of unusual statements, the Mayo Clinic forcefully rebutted Joyner’s claims in some detail: “Dr. Joyner’s lawsuit is yet another manifestation of his refusal to recognize or accept responsibility for his inappropriate behaviors,” it told Becker’s Hospital Review.

In a June letter to colleagues, the institution’s communications head said Dr. Joyner was not punished over his transgender athlete comments but instead because he mistreated coworkers and made “unprofessional” comments to The New York Times.

Dr. Joyner, a prominent physiologist and anesthesiologist who has worked for Mayo Clinic for 36 years, has become a cause célèbre in academic and free-speech circles over the past several months.

Two conversations with journalists appear to be at the heart of the Mayo Clinic’s complaints.

First, a 2022 New York Times article about transgender athletes quoted him about how testosterone dramatically affects performance in males: “There are social aspects to sport, but physiology and biology underpin it. Testosterone is the 800-pound gorilla.”

“The language was at best, insensitive. At worst, transphobic,” an LGBTQ advocate told a TV news station in Rochester, Minn., where the Mayo Clinic is based. The article didn’t elaborate on why the advocate believed the language could be transphobic.

Then, a CNN story in 2023 noted that Dr. Joyner has studied convalescent plasma as a treatment for COVID-19 and quoted him about how the National Institutes of Health declined to take a stand on the use of the therapy: “Joyner said he’s ‘frustrated’ with the NIH’s ‘bureaucratic rope-a-dope,’ calling the agency’s guidelines ‘a wet blanket.’ ”

It is not unusual for medical researchers to comment bluntly to the media about federal agencies.

For example, a 2020 New York Times story that unraveled the Trump Administration’s apparent mischaracterization of Dr. Joyner’s research into convalescent plasma quoted a University of Pittsburgh physician as saying, “For the first time ever, I feel like official people in communications and people at the FDA grossly misrepresented data about a therapy.”

In a March 5 letter, a Mayo Clinic administrator wrote to Dr. Joyner to complain that his comments regarding the NIH were an example of his “problematic” use of “idiomatic language” that “reflects poorly on Mayo Clinic’s brand and reputation.” A paragraph in the letter is redacted in the version posted by the Foundation for Individual Rights and Expression, which supports Dr. Joyner.

The letter adds that Dr. Joyner’s comments to The New York Times “were problematic in the media and the LGBTQI+ community at Mayo Clinic.” The letter, which didn’t elaborate about the blowback, also says that “concerns remain with disrespectful communications with colleagues who describe your tone as unpleasant and having a ‘bullying’ quality to it.”

Kellie Miller, one of Dr. Joyner’s attorneys, noted in a statement that “Dr. Joyner’s personnel file is free of any documentation of Mayo’s ongoing and vague allegations of bullying and unprofessionalism with colleagues.”

The letter also ordered Dr. Joyner to not be rude or criticize the work of others and repair his relationship with Mayo Clinic’s public affairs staff: “This will take individual effort on your part.” It also ordered him to “discuss approved topics only” with reporters, “stick to prescribed messaging,” and not resist if the public affairs department doesn’t let him be interviewed: “Accept ‘no’ for an answer and move forward.”

Medical institutions often monitor how their employees interact with the media in order to control “messaging.” But firm rules at academic medical institutions like the Mayo Clinic may run the risk of running afoul of the tenets of academic freedom.

The institution and its CEO then retaliated by calling his claims “unprofessional,” according to the lawsuit, which provided no further details about the situation.

In a statement, the Mayo Clinic said it “hired an outside attorney to investigate these concerns. The attorney, who is now a federal judge, found there was no retaliation and that Dr. Joyner had engaged in a pattern of asserting inflammatory allegations grounded almost entirely in speculation.”

A petition signed by dozens of professors demands that Mayo Clinic “revoke the penalties and constraints it has imposed on him.”

“Dr. Joyner, a faculty member at a medical school that avows a commitment to academic freedom and to free expression, did not exceed the limits of his expertise in any of his statements to the press that led to these sanctions,” they wrote. “At no time did he claim to be speaking for the Mayo Clinic, and his remarks were well within the mainstream of the range of scientific opinion on topics in which he is expert.”

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

An anesthesiologist is suing the Mayo Clinic after it allegedly ordered him to stick to “prescribed messaging” after his outspoken comments about transgender athletes and a federal agency’s sluggishness regarding a COVID-19 treatment.

Michael J. Joyner, MD, claims that the Mayo Clinic violated its own policies by muzzling him, slapping him with an unpaid 1-week suspension, and labeling his comments to the media “unprofessional.”

In his Nov. 13 lawsuit, filed in Minnesota state court, Dr. Joyner asks that a judge order Mayo Clinic to stop its “retaliation and interference” with his “communications about his research.” He that claims the retaliation stems from his 2020 report about a Mayo Clinic business partner’s “attempt to unlawfully access and use protected patient data.”

Medical institutions often refuse to comment on pending litigation. But in a pair of unusual statements, the Mayo Clinic forcefully rebutted Joyner’s claims in some detail: “Dr. Joyner’s lawsuit is yet another manifestation of his refusal to recognize or accept responsibility for his inappropriate behaviors,” it told Becker’s Hospital Review.

In a June letter to colleagues, the institution’s communications head said Dr. Joyner was not punished over his transgender athlete comments but instead because he mistreated coworkers and made “unprofessional” comments to The New York Times.

Dr. Joyner, a prominent physiologist and anesthesiologist who has worked for Mayo Clinic for 36 years, has become a cause célèbre in academic and free-speech circles over the past several months.

Two conversations with journalists appear to be at the heart of the Mayo Clinic’s complaints.

First, a 2022 New York Times article about transgender athletes quoted him about how testosterone dramatically affects performance in males: “There are social aspects to sport, but physiology and biology underpin it. Testosterone is the 800-pound gorilla.”

“The language was at best, insensitive. At worst, transphobic,” an LGBTQ advocate told a TV news station in Rochester, Minn., where the Mayo Clinic is based. The article didn’t elaborate on why the advocate believed the language could be transphobic.

Then, a CNN story in 2023 noted that Dr. Joyner has studied convalescent plasma as a treatment for COVID-19 and quoted him about how the National Institutes of Health declined to take a stand on the use of the therapy: “Joyner said he’s ‘frustrated’ with the NIH’s ‘bureaucratic rope-a-dope,’ calling the agency’s guidelines ‘a wet blanket.’ ”

It is not unusual for medical researchers to comment bluntly to the media about federal agencies.

For example, a 2020 New York Times story that unraveled the Trump Administration’s apparent mischaracterization of Dr. Joyner’s research into convalescent plasma quoted a University of Pittsburgh physician as saying, “For the first time ever, I feel like official people in communications and people at the FDA grossly misrepresented data about a therapy.”

In a March 5 letter, a Mayo Clinic administrator wrote to Dr. Joyner to complain that his comments regarding the NIH were an example of his “problematic” use of “idiomatic language” that “reflects poorly on Mayo Clinic’s brand and reputation.” A paragraph in the letter is redacted in the version posted by the Foundation for Individual Rights and Expression, which supports Dr. Joyner.

The letter adds that Dr. Joyner’s comments to The New York Times “were problematic in the media and the LGBTQI+ community at Mayo Clinic.” The letter, which didn’t elaborate about the blowback, also says that “concerns remain with disrespectful communications with colleagues who describe your tone as unpleasant and having a ‘bullying’ quality to it.”

Kellie Miller, one of Dr. Joyner’s attorneys, noted in a statement that “Dr. Joyner’s personnel file is free of any documentation of Mayo’s ongoing and vague allegations of bullying and unprofessionalism with colleagues.”

The letter also ordered Dr. Joyner to not be rude or criticize the work of others and repair his relationship with Mayo Clinic’s public affairs staff: “This will take individual effort on your part.” It also ordered him to “discuss approved topics only” with reporters, “stick to prescribed messaging,” and not resist if the public affairs department doesn’t let him be interviewed: “Accept ‘no’ for an answer and move forward.”

Medical institutions often monitor how their employees interact with the media in order to control “messaging.” But firm rules at academic medical institutions like the Mayo Clinic may run the risk of running afoul of the tenets of academic freedom.

The institution and its CEO then retaliated by calling his claims “unprofessional,” according to the lawsuit, which provided no further details about the situation.

In a statement, the Mayo Clinic said it “hired an outside attorney to investigate these concerns. The attorney, who is now a federal judge, found there was no retaliation and that Dr. Joyner had engaged in a pattern of asserting inflammatory allegations grounded almost entirely in speculation.”

A petition signed by dozens of professors demands that Mayo Clinic “revoke the penalties and constraints it has imposed on him.”

“Dr. Joyner, a faculty member at a medical school that avows a commitment to academic freedom and to free expression, did not exceed the limits of his expertise in any of his statements to the press that led to these sanctions,” they wrote. “At no time did he claim to be speaking for the Mayo Clinic, and his remarks were well within the mainstream of the range of scientific opinion on topics in which he is expert.”

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

An anesthesiologist is suing the Mayo Clinic after it allegedly ordered him to stick to “prescribed messaging” after his outspoken comments about transgender athletes and a federal agency’s sluggishness regarding a COVID-19 treatment.

Michael J. Joyner, MD, claims that the Mayo Clinic violated its own policies by muzzling him, slapping him with an unpaid 1-week suspension, and labeling his comments to the media “unprofessional.”

In his Nov. 13 lawsuit, filed in Minnesota state court, Dr. Joyner asks that a judge order Mayo Clinic to stop its “retaliation and interference” with his “communications about his research.” He that claims the retaliation stems from his 2020 report about a Mayo Clinic business partner’s “attempt to unlawfully access and use protected patient data.”

Medical institutions often refuse to comment on pending litigation. But in a pair of unusual statements, the Mayo Clinic forcefully rebutted Joyner’s claims in some detail: “Dr. Joyner’s lawsuit is yet another manifestation of his refusal to recognize or accept responsibility for his inappropriate behaviors,” it told Becker’s Hospital Review.

In a June letter to colleagues, the institution’s communications head said Dr. Joyner was not punished over his transgender athlete comments but instead because he mistreated coworkers and made “unprofessional” comments to The New York Times.

Dr. Joyner, a prominent physiologist and anesthesiologist who has worked for Mayo Clinic for 36 years, has become a cause célèbre in academic and free-speech circles over the past several months.

Two conversations with journalists appear to be at the heart of the Mayo Clinic’s complaints.

First, a 2022 New York Times article about transgender athletes quoted him about how testosterone dramatically affects performance in males: “There are social aspects to sport, but physiology and biology underpin it. Testosterone is the 800-pound gorilla.”

“The language was at best, insensitive. At worst, transphobic,” an LGBTQ advocate told a TV news station in Rochester, Minn., where the Mayo Clinic is based. The article didn’t elaborate on why the advocate believed the language could be transphobic.

Then, a CNN story in 2023 noted that Dr. Joyner has studied convalescent plasma as a treatment for COVID-19 and quoted him about how the National Institutes of Health declined to take a stand on the use of the therapy: “Joyner said he’s ‘frustrated’ with the NIH’s ‘bureaucratic rope-a-dope,’ calling the agency’s guidelines ‘a wet blanket.’ ”

It is not unusual for medical researchers to comment bluntly to the media about federal agencies.

For example, a 2020 New York Times story that unraveled the Trump Administration’s apparent mischaracterization of Dr. Joyner’s research into convalescent plasma quoted a University of Pittsburgh physician as saying, “For the first time ever, I feel like official people in communications and people at the FDA grossly misrepresented data about a therapy.”

In a March 5 letter, a Mayo Clinic administrator wrote to Dr. Joyner to complain that his comments regarding the NIH were an example of his “problematic” use of “idiomatic language” that “reflects poorly on Mayo Clinic’s brand and reputation.” A paragraph in the letter is redacted in the version posted by the Foundation for Individual Rights and Expression, which supports Dr. Joyner.

The letter adds that Dr. Joyner’s comments to The New York Times “were problematic in the media and the LGBTQI+ community at Mayo Clinic.” The letter, which didn’t elaborate about the blowback, also says that “concerns remain with disrespectful communications with colleagues who describe your tone as unpleasant and having a ‘bullying’ quality to it.”

Kellie Miller, one of Dr. Joyner’s attorneys, noted in a statement that “Dr. Joyner’s personnel file is free of any documentation of Mayo’s ongoing and vague allegations of bullying and unprofessionalism with colleagues.”

The letter also ordered Dr. Joyner to not be rude or criticize the work of others and repair his relationship with Mayo Clinic’s public affairs staff: “This will take individual effort on your part.” It also ordered him to “discuss approved topics only” with reporters, “stick to prescribed messaging,” and not resist if the public affairs department doesn’t let him be interviewed: “Accept ‘no’ for an answer and move forward.”

Medical institutions often monitor how their employees interact with the media in order to control “messaging.” But firm rules at academic medical institutions like the Mayo Clinic may run the risk of running afoul of the tenets of academic freedom.

The institution and its CEO then retaliated by calling his claims “unprofessional,” according to the lawsuit, which provided no further details about the situation.

In a statement, the Mayo Clinic said it “hired an outside attorney to investigate these concerns. The attorney, who is now a federal judge, found there was no retaliation and that Dr. Joyner had engaged in a pattern of asserting inflammatory allegations grounded almost entirely in speculation.”

A petition signed by dozens of professors demands that Mayo Clinic “revoke the penalties and constraints it has imposed on him.”

“Dr. Joyner, a faculty member at a medical school that avows a commitment to academic freedom and to free expression, did not exceed the limits of his expertise in any of his statements to the press that led to these sanctions,” they wrote. “At no time did he claim to be speaking for the Mayo Clinic, and his remarks were well within the mainstream of the range of scientific opinion on topics in which he is expert.”

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