Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.

After an initial first dose of a CGRP mAb treatment, many patients ask whether a suboptimal response necessitates switching to another agent or whether a second (or third) dose should be given first. Eptinezumab is an intravenously administered mAb that is repeated every 12 weeks. Schim and colleagues present post hoc data for patients who initially had a minimally beneficial response to eptinezumab and received a second dose at week 13.
 

The authors define a suboptimal response as having less then a 50% decrease in monthly migraine days after 12 weeks. There were two pooled samples of patients — those who received 100 mg eptinezumab and those who received a 300 mg dose. Approximately 45% of patients in the pivotal trials of eptinezumab (PROMISE-1 and -2) were considered suboptimal responders, and 33%-37% of those suboptimal responders had a more than 50% decrease of their monthly migraine days after a second dose (week 24).
 

Further analysis determined predictive factors that favored a second dose response. The most prominent (and arguably most obvious) predictive factor was a favorable response after the first dose; the greater percent change in monthly migraine days after the first dose was proportional to the response after the second dose. Change in the Headache Impact Test (HIT-6) disability score after the first dose was also seen to be a strong predictive factor for improvement after the second dose.

When we discuss continuation of medications with our patients, especially when they have a suboptimal response, we should first keep in mind the degree of improvement that the patient initially had. There can be benefit from further treatment with the same medication; however, if the response truly was minimal, it may be better to consider another treatment option.

Practically every patient taking a preventive medication is taking at least one acute medication as well. Even the best preventive medication is not a guarantee that further exacerbations will not occur, and our patients will still need some acute treatment option even when their preventive medications are very effective. The study by Ambrosini and colleagues specifically shows how effective a preventive medication can be, specifically in allowing the patient to use fewer acute medications over time in a population of patients who have been resistant to two to four treatments.
 

Galcanezumab is a once-monthly mAb for the prevention of migraine. The authors of this study compared the acute use of medications for migraine in both the randomized and open-label stages of a study assessing treatment-refractory patients. A total of 462 patients were enrolled who were all resistant to two to four standard-of-care migraine-preventive medications that had been stopped either because of lack of efficacy or tolerance. The double-blind stage lasted 3 months; the open-label stage lasted another 3 months.
 

The treatment group was seen to use significantly fewer acute medications after just the first month and continued to improve through month 3. In the open-label phase, a similar improvement was noted in patients transitioning from placebo. In addition to acute medication use, emergency department use for migraine treatment was decreased significantly as well, by more than two thirds in month 3.

Migraine prevention will always remain the key ingredient for improvement for patients with higher frequencies of migraine, and adequate prevention will allow for the lower use of acute medications, and for less healthcare system use in general.
 

Most practitioners recommend migraine-specific medications for the acute treatment of migraine. Since the advent of sumatriptan, this has usually meant a triptan medication. However, a significant percentage of the population (up to 44% in one study) are either intolerant to, contraindicated for, or respond insufficiently to triptan medications. This can either be due to a strong triptan side effect (worsened nausea; tightness/soreness of the muscles of the chest, shoulders, and neck), having cardiovascular risk factors, or not responding adequately 2 hours after treatment. The study by Lipton and colleagues specifically assessed the efficacy of ubrogepant in this population.
 

Ubrogepant is a small-molecule CGRP antagonist for the acute treatment of migraine. Although somewhat controversial, most practitioners use ubrogepant in patients with some cardiovascular risk, a situation where they would be more likely to avoid the use of triptans. The study authors pooled post hoc data from the pivotal ubrogepant trials (ACHIEVE-1 and -2) to isolate patients with insufficient response to triptans, and their primary outcome was improvement in function 2 hours after medication dose.
 

Participants in the pivotal trials were separated into three groups: triptan responders, triptan insufficient responders, and triptan-naive patients. Triptan response was defined as achieving pain freedom 2 hours after medication dose. Both those who had an insufficient response and those who no longer use the triptan owing to intolerance or contraindications were included in the group with insufficient triptan response. Function improvement was defined as the primary outcome on the basis of a 4-point response scale (0 = no disability, 1 = mildly impaired, 2 = moderately impaired, 3 = severely impaired). In addition, patients were asked to report scores of satisfaction with the medication (yes or no) at 2 and 24 hours and their impression of overall change at 2 hours using a 7-point scale.
 

The population group of triptan insufficient responders (451 patients) had significant improvement in the primary outcome functional disability at 2, 4, and 7 hours after receipt of medications, but there was no statistical difference at 1 hour. This was similar when comparing those with intolerance to triptans, insufficient response to triptans, or contraindications for triptans. The secondary outcomes of satisfaction and global impression of change were also statistically improved in the insufficient-responders group. No additional tolerance issues or adverse events were noted in this group either.

It would certainly be worth considering the use of a gepant acute medication, such as ubrogepant, in patients who are intolerant to or inadequately treated by triptan medications. There still is much to learn about cardiovascular risk and the use of CGRP antagonists, and although no adverse events were noted, more data may be necessary to widely prescribe this class in higher-risk patients.

Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.

After an initial first dose of a CGRP mAb treatment, many patients ask whether a suboptimal response necessitates switching to another agent or whether a second (or third) dose should be given first. Eptinezumab is an intravenously administered mAb that is repeated every 12 weeks. Schim and colleagues present post hoc data for patients who initially had a minimally beneficial response to eptinezumab and received a second dose at week 13.
 

The authors define a suboptimal response as having less then a 50% decrease in monthly migraine days after 12 weeks. There were two pooled samples of patients — those who received 100 mg eptinezumab and those who received a 300 mg dose. Approximately 45% of patients in the pivotal trials of eptinezumab (PROMISE-1 and -2) were considered suboptimal responders, and 33%-37% of those suboptimal responders had a more than 50% decrease of their monthly migraine days after a second dose (week 24).
 

Further analysis determined predictive factors that favored a second dose response. The most prominent (and arguably most obvious) predictive factor was a favorable response after the first dose; the greater percent change in monthly migraine days after the first dose was proportional to the response after the second dose. Change in the Headache Impact Test (HIT-6) disability score after the first dose was also seen to be a strong predictive factor for improvement after the second dose.

When we discuss continuation of medications with our patients, especially when they have a suboptimal response, we should first keep in mind the degree of improvement that the patient initially had. There can be benefit from further treatment with the same medication; however, if the response truly was minimal, it may be better to consider another treatment option.

Practically every patient taking a preventive medication is taking at least one acute medication as well. Even the best preventive medication is not a guarantee that further exacerbations will not occur, and our patients will still need some acute treatment option even when their preventive medications are very effective. The study by Ambrosini and colleagues specifically shows how effective a preventive medication can be, specifically in allowing the patient to use fewer acute medications over time in a population of patients who have been resistant to two to four treatments.
 

Galcanezumab is a once-monthly mAb for the prevention of migraine. The authors of this study compared the acute use of medications for migraine in both the randomized and open-label stages of a study assessing treatment-refractory patients. A total of 462 patients were enrolled who were all resistant to two to four standard-of-care migraine-preventive medications that had been stopped either because of lack of efficacy or tolerance. The double-blind stage lasted 3 months; the open-label stage lasted another 3 months.
 

The treatment group was seen to use significantly fewer acute medications after just the first month and continued to improve through month 3. In the open-label phase, a similar improvement was noted in patients transitioning from placebo. In addition to acute medication use, emergency department use for migraine treatment was decreased significantly as well, by more than two thirds in month 3.

Migraine prevention will always remain the key ingredient for improvement for patients with higher frequencies of migraine, and adequate prevention will allow for the lower use of acute medications, and for less healthcare system use in general.
 

Most practitioners recommend migraine-specific medications for the acute treatment of migraine. Since the advent of sumatriptan, this has usually meant a triptan medication. However, a significant percentage of the population (up to 44% in one study) are either intolerant to, contraindicated for, or respond insufficiently to triptan medications. This can either be due to a strong triptan side effect (worsened nausea; tightness/soreness of the muscles of the chest, shoulders, and neck), having cardiovascular risk factors, or not responding adequately 2 hours after treatment. The study by Lipton and colleagues specifically assessed the efficacy of ubrogepant in this population.
 

Ubrogepant is a small-molecule CGRP antagonist for the acute treatment of migraine. Although somewhat controversial, most practitioners use ubrogepant in patients with some cardiovascular risk, a situation where they would be more likely to avoid the use of triptans. The study authors pooled post hoc data from the pivotal ubrogepant trials (ACHIEVE-1 and -2) to isolate patients with insufficient response to triptans, and their primary outcome was improvement in function 2 hours after medication dose.
 

Participants in the pivotal trials were separated into three groups: triptan responders, triptan insufficient responders, and triptan-naive patients. Triptan response was defined as achieving pain freedom 2 hours after medication dose. Both those who had an insufficient response and those who no longer use the triptan owing to intolerance or contraindications were included in the group with insufficient triptan response. Function improvement was defined as the primary outcome on the basis of a 4-point response scale (0 = no disability, 1 = mildly impaired, 2 = moderately impaired, 3 = severely impaired). In addition, patients were asked to report scores of satisfaction with the medication (yes or no) at 2 and 24 hours and their impression of overall change at 2 hours using a 7-point scale.
 

The population group of triptan insufficient responders (451 patients) had significant improvement in the primary outcome functional disability at 2, 4, and 7 hours after receipt of medications, but there was no statistical difference at 1 hour. This was similar when comparing those with intolerance to triptans, insufficient response to triptans, or contraindications for triptans. The secondary outcomes of satisfaction and global impression of change were also statistically improved in the insufficient-responders group. No additional tolerance issues or adverse events were noted in this group either.

It would certainly be worth considering the use of a gepant acute medication, such as ubrogepant, in patients who are intolerant to or inadequately treated by triptan medications. There still is much to learn about cardiovascular risk and the use of CGRP antagonists, and although no adverse events were noted, more data may be necessary to widely prescribe this class in higher-risk patients.

Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.

After an initial first dose of a CGRP mAb treatment, many patients ask whether a suboptimal response necessitates switching to another agent or whether a second (or third) dose should be given first. Eptinezumab is an intravenously administered mAb that is repeated every 12 weeks. Schim and colleagues present post hoc data for patients who initially had a minimally beneficial response to eptinezumab and received a second dose at week 13.
 

The authors define a suboptimal response as having less then a 50% decrease in monthly migraine days after 12 weeks. There were two pooled samples of patients — those who received 100 mg eptinezumab and those who received a 300 mg dose. Approximately 45% of patients in the pivotal trials of eptinezumab (PROMISE-1 and -2) were considered suboptimal responders, and 33%-37% of those suboptimal responders had a more than 50% decrease of their monthly migraine days after a second dose (week 24).
 

Further analysis determined predictive factors that favored a second dose response. The most prominent (and arguably most obvious) predictive factor was a favorable response after the first dose; the greater percent change in monthly migraine days after the first dose was proportional to the response after the second dose. Change in the Headache Impact Test (HIT-6) disability score after the first dose was also seen to be a strong predictive factor for improvement after the second dose.

When we discuss continuation of medications with our patients, especially when they have a suboptimal response, we should first keep in mind the degree of improvement that the patient initially had. There can be benefit from further treatment with the same medication; however, if the response truly was minimal, it may be better to consider another treatment option.

Practically every patient taking a preventive medication is taking at least one acute medication as well. Even the best preventive medication is not a guarantee that further exacerbations will not occur, and our patients will still need some acute treatment option even when their preventive medications are very effective. The study by Ambrosini and colleagues specifically shows how effective a preventive medication can be, specifically in allowing the patient to use fewer acute medications over time in a population of patients who have been resistant to two to four treatments.
 

Galcanezumab is a once-monthly mAb for the prevention of migraine. The authors of this study compared the acute use of medications for migraine in both the randomized and open-label stages of a study assessing treatment-refractory patients. A total of 462 patients were enrolled who were all resistant to two to four standard-of-care migraine-preventive medications that had been stopped either because of lack of efficacy or tolerance. The double-blind stage lasted 3 months; the open-label stage lasted another 3 months.
 

The treatment group was seen to use significantly fewer acute medications after just the first month and continued to improve through month 3. In the open-label phase, a similar improvement was noted in patients transitioning from placebo. In addition to acute medication use, emergency department use for migraine treatment was decreased significantly as well, by more than two thirds in month 3.

Migraine prevention will always remain the key ingredient for improvement for patients with higher frequencies of migraine, and adequate prevention will allow for the lower use of acute medications, and for less healthcare system use in general.
 

Most practitioners recommend migraine-specific medications for the acute treatment of migraine. Since the advent of sumatriptan, this has usually meant a triptan medication. However, a significant percentage of the population (up to 44% in one study) are either intolerant to, contraindicated for, or respond insufficiently to triptan medications. This can either be due to a strong triptan side effect (worsened nausea; tightness/soreness of the muscles of the chest, shoulders, and neck), having cardiovascular risk factors, or not responding adequately 2 hours after treatment. The study by Lipton and colleagues specifically assessed the efficacy of ubrogepant in this population.
 

Ubrogepant is a small-molecule CGRP antagonist for the acute treatment of migraine. Although somewhat controversial, most practitioners use ubrogepant in patients with some cardiovascular risk, a situation where they would be more likely to avoid the use of triptans. The study authors pooled post hoc data from the pivotal ubrogepant trials (ACHIEVE-1 and -2) to isolate patients with insufficient response to triptans, and their primary outcome was improvement in function 2 hours after medication dose.
 

Participants in the pivotal trials were separated into three groups: triptan responders, triptan insufficient responders, and triptan-naive patients. Triptan response was defined as achieving pain freedom 2 hours after medication dose. Both those who had an insufficient response and those who no longer use the triptan owing to intolerance or contraindications were included in the group with insufficient triptan response. Function improvement was defined as the primary outcome on the basis of a 4-point response scale (0 = no disability, 1 = mildly impaired, 2 = moderately impaired, 3 = severely impaired). In addition, patients were asked to report scores of satisfaction with the medication (yes or no) at 2 and 24 hours and their impression of overall change at 2 hours using a 7-point scale.
 

The population group of triptan insufficient responders (451 patients) had significant improvement in the primary outcome functional disability at 2, 4, and 7 hours after receipt of medications, but there was no statistical difference at 1 hour. This was similar when comparing those with intolerance to triptans, insufficient response to triptans, or contraindications for triptans. The secondary outcomes of satisfaction and global impression of change were also statistically improved in the insufficient-responders group. No additional tolerance issues or adverse events were noted in this group either.

It would certainly be worth considering the use of a gepant acute medication, such as ubrogepant, in patients who are intolerant to or inadequately treated by triptan medications. There still is much to learn about cardiovascular risk and the use of CGRP antagonists, and although no adverse events were noted, more data may be necessary to widely prescribe this class in higher-risk patients.

Non-Hispanic White children were more likely to receive diagnostic imaging at children’s hospitals’ emergency departments across the United States than were Hispanic children and non-Hispanic Black children, according to a large study published in JAMA Network Open.

Researchers found that, the more the percentage of children from minority groups cared for by a hospital increased, the wider the imaging gap between those children and non-Hispanic White children.

The cross-sectional study, led by Margaret E. Samuels-Kalow, MD, MPhil, MSHP, with the department of emergency medicine, Massachusetts General Hospital and Harvard Medical School in Boston, included 38 children’s hospitals and more than 12 million ED visits.

“These findings emphasize the urgent need for interventions at the hospital level to improve equity in imaging in pediatric emergency medicine,” the authors write.

Patients included in the study were younger than 18 and visited an ED from January 2016 through December 2019. Data were pulled from the Pediatric Health Information System.

Of the more than 12 million visits in this study, 3.5 million (28.7%) involved at least one diagnostic imaging test.

Diagnostic imaging was performed in 1.5 million visits (34.2%) for non-Hispanic White children; 790,961 (24.6%) for non-Hispanic Black children; and 907,222 (26.1%) for Hispanic children (P < .001).

Non-Hispanic Black children were consistently less likely to get diagnostic imaging than non-Hispanic White counterparts at every hospital in the study, no matter the imaging modality: radiography, ultrasonography, computed tomography, or magnetic resonance imaging.

Hispanic patients were generally less likely to get imaging than non-Hispanic White patients, though results were less consistent for ultrasound and MRI.

In a sensitivity analysis, when looking at imaging from patients’ first visit across the study cohort, non-Hispanic Black children were significantly less likely to get imaging than non-Hispanic White children (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.79).

“This remained significant even after adjustment for a priori specified confounders including hospital propensity to image,” the authors write.

Authors acknowledge that it is possible that some of the differences may be attributable to the patient mix regarding severity of cases or indications for imaging by hospital, but they note that all models were adjusted for diagnosis-related group and other potential confounders.

This study did not assess whether one group is being overtested. Researchers also note that higher rates of imaging do not necessarily indicate higher quality of care.

However, the authors note, previous research has suggested overtesting of non-Hispanic White patients for head CT and chest pain, as well as patterns of overtreatment of non-Hispanic White patients who have bronchiolitis or viral upper respiratory tract infections.

Medell Briggs-Malonson, MD, MPH, chief of health equity, diversity and inclusion for the University of California, Los Angeles, Hospital and Clinic System, who was not part of the study, said in an interview “this all rings true.”

“This is not the first study we have had in either the pediatric or adult populations that shows disparate levels of care as well as health outcomes. Now we are starting to be able to measure it,” she said.

This study is further evidence of medical racism, she says, and highlights that it’s not the hospital choice or the insurance type affecting the numbers, she said.

“When you control for those factors, it looks to be it’s only due to race and that’s because of the very deep levels of implicit bias as well as explicit bias that we still have in our health systems and even in our providers,” said Dr. Briggs-Malonson, who is also an associate professor of emergency medicine at UCLA. “It’s incredibly important to identify and immediately address.”

What can be done?

Changing these patterns starts with knowing the numbers, the authors write.

“Hospitals should measure their own differences in imaging rates and increase awareness of existing areas of differential treatment as a starting point for improvement,” Dr. Samuels-Kalow and coauthors say.

Dr. Briggs-Malonson added that guidelines are very clear about when children should get imaging. Adhering to evidence-based guidelines can help avoid variations in care from external factors.

“If children are not receiving the absolute best comprehensive evaluation in the emergency department that they deserve, we can miss many different illnesses, which can lead to worse outcomes,” she noted.

As for what might motivate lack of imaging, Dr. Briggs-Malonson pointed to longstanding trends of providers thinking complaints raised by minority patients may not be as severe as they report. Conversely, in caring for White patients there may be a feeling that more tests and imaging may be better out of more fear of missing something, she said.

At UCLA, she says, dashboards have been developed to track statistics on care by age, race, ethnicity, language, insurance type, etc., though not specifically in pediatric imaging, to assess and address any care inequities.

Summer L. Kaplan, MD, MS, director of emergency radiology at Children’s Hospital of Philadelphia, who also was not part of the study, said the finding of racial disparities in pediatric ED imaging provides evidence that gaps still exist in providing the best care to all children and families seeking emergency care.

“However, it is important to recognize that more imaging does not equal better care,” she said. “More imaging may be associated with unnecessary, low-value tests that may add radiation and other risks but do not improve care.”

She said higher rates of imaging may occur when patients present early in the course of a disease, when the differential diagnosis remains broad.

If families have delayed seeking care because of time constraints, transportation problems, cost of care, or mistrust of the health system, children may present later in the course of a disease and require less imaging for a diagnosis, she explained.

“This paper offers a valuable look at the inequities that exist in pediatric emergency imaging use, and further research will be essential to understand and address the causes of these differences,” Dr. Kaplan said.

A coauthor reported compensation as a member of a Medical Review Committee for Highmark. Other coauthors reported grants from the U.S. Agency for Healthcare Research and Quality outside the submitted work. Dr. Briggs-Malonson and Dr. Kaplan reported no relevant financial relationships.

Non-Hispanic White children were more likely to receive diagnostic imaging at children’s hospitals’ emergency departments across the United States than were Hispanic children and non-Hispanic Black children, according to a large study published in JAMA Network Open.

Researchers found that, the more the percentage of children from minority groups cared for by a hospital increased, the wider the imaging gap between those children and non-Hispanic White children.

The cross-sectional study, led by Margaret E. Samuels-Kalow, MD, MPhil, MSHP, with the department of emergency medicine, Massachusetts General Hospital and Harvard Medical School in Boston, included 38 children’s hospitals and more than 12 million ED visits.

“These findings emphasize the urgent need for interventions at the hospital level to improve equity in imaging in pediatric emergency medicine,” the authors write.

Patients included in the study were younger than 18 and visited an ED from January 2016 through December 2019. Data were pulled from the Pediatric Health Information System.

Of the more than 12 million visits in this study, 3.5 million (28.7%) involved at least one diagnostic imaging test.

Diagnostic imaging was performed in 1.5 million visits (34.2%) for non-Hispanic White children; 790,961 (24.6%) for non-Hispanic Black children; and 907,222 (26.1%) for Hispanic children (P < .001).

Non-Hispanic Black children were consistently less likely to get diagnostic imaging than non-Hispanic White counterparts at every hospital in the study, no matter the imaging modality: radiography, ultrasonography, computed tomography, or magnetic resonance imaging.

Hispanic patients were generally less likely to get imaging than non-Hispanic White patients, though results were less consistent for ultrasound and MRI.

In a sensitivity analysis, when looking at imaging from patients’ first visit across the study cohort, non-Hispanic Black children were significantly less likely to get imaging than non-Hispanic White children (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.79).

“This remained significant even after adjustment for a priori specified confounders including hospital propensity to image,” the authors write.

Authors acknowledge that it is possible that some of the differences may be attributable to the patient mix regarding severity of cases or indications for imaging by hospital, but they note that all models were adjusted for diagnosis-related group and other potential confounders.

This study did not assess whether one group is being overtested. Researchers also note that higher rates of imaging do not necessarily indicate higher quality of care.

However, the authors note, previous research has suggested overtesting of non-Hispanic White patients for head CT and chest pain, as well as patterns of overtreatment of non-Hispanic White patients who have bronchiolitis or viral upper respiratory tract infections.

Medell Briggs-Malonson, MD, MPH, chief of health equity, diversity and inclusion for the University of California, Los Angeles, Hospital and Clinic System, who was not part of the study, said in an interview “this all rings true.”

“This is not the first study we have had in either the pediatric or adult populations that shows disparate levels of care as well as health outcomes. Now we are starting to be able to measure it,” she said.

This study is further evidence of medical racism, she says, and highlights that it’s not the hospital choice or the insurance type affecting the numbers, she said.

“When you control for those factors, it looks to be it’s only due to race and that’s because of the very deep levels of implicit bias as well as explicit bias that we still have in our health systems and even in our providers,” said Dr. Briggs-Malonson, who is also an associate professor of emergency medicine at UCLA. “It’s incredibly important to identify and immediately address.”

What can be done?

Changing these patterns starts with knowing the numbers, the authors write.

“Hospitals should measure their own differences in imaging rates and increase awareness of existing areas of differential treatment as a starting point for improvement,” Dr. Samuels-Kalow and coauthors say.

Dr. Briggs-Malonson added that guidelines are very clear about when children should get imaging. Adhering to evidence-based guidelines can help avoid variations in care from external factors.

“If children are not receiving the absolute best comprehensive evaluation in the emergency department that they deserve, we can miss many different illnesses, which can lead to worse outcomes,” she noted.

As for what might motivate lack of imaging, Dr. Briggs-Malonson pointed to longstanding trends of providers thinking complaints raised by minority patients may not be as severe as they report. Conversely, in caring for White patients there may be a feeling that more tests and imaging may be better out of more fear of missing something, she said.

At UCLA, she says, dashboards have been developed to track statistics on care by age, race, ethnicity, language, insurance type, etc., though not specifically in pediatric imaging, to assess and address any care inequities.

Summer L. Kaplan, MD, MS, director of emergency radiology at Children’s Hospital of Philadelphia, who also was not part of the study, said the finding of racial disparities in pediatric ED imaging provides evidence that gaps still exist in providing the best care to all children and families seeking emergency care.

“However, it is important to recognize that more imaging does not equal better care,” she said. “More imaging may be associated with unnecessary, low-value tests that may add radiation and other risks but do not improve care.”

She said higher rates of imaging may occur when patients present early in the course of a disease, when the differential diagnosis remains broad.

If families have delayed seeking care because of time constraints, transportation problems, cost of care, or mistrust of the health system, children may present later in the course of a disease and require less imaging for a diagnosis, she explained.

“This paper offers a valuable look at the inequities that exist in pediatric emergency imaging use, and further research will be essential to understand and address the causes of these differences,” Dr. Kaplan said.

A coauthor reported compensation as a member of a Medical Review Committee for Highmark. Other coauthors reported grants from the U.S. Agency for Healthcare Research and Quality outside the submitted work. Dr. Briggs-Malonson and Dr. Kaplan reported no relevant financial relationships.

Non-Hispanic White children were more likely to receive diagnostic imaging at children’s hospitals’ emergency departments across the United States than were Hispanic children and non-Hispanic Black children, according to a large study published in JAMA Network Open.

Researchers found that, the more the percentage of children from minority groups cared for by a hospital increased, the wider the imaging gap between those children and non-Hispanic White children.

The cross-sectional study, led by Margaret E. Samuels-Kalow, MD, MPhil, MSHP, with the department of emergency medicine, Massachusetts General Hospital and Harvard Medical School in Boston, included 38 children’s hospitals and more than 12 million ED visits.

“These findings emphasize the urgent need for interventions at the hospital level to improve equity in imaging in pediatric emergency medicine,” the authors write.

Patients included in the study were younger than 18 and visited an ED from January 2016 through December 2019. Data were pulled from the Pediatric Health Information System.

Of the more than 12 million visits in this study, 3.5 million (28.7%) involved at least one diagnostic imaging test.

Diagnostic imaging was performed in 1.5 million visits (34.2%) for non-Hispanic White children; 790,961 (24.6%) for non-Hispanic Black children; and 907,222 (26.1%) for Hispanic children (P < .001).

Non-Hispanic Black children were consistently less likely to get diagnostic imaging than non-Hispanic White counterparts at every hospital in the study, no matter the imaging modality: radiography, ultrasonography, computed tomography, or magnetic resonance imaging.

Hispanic patients were generally less likely to get imaging than non-Hispanic White patients, though results were less consistent for ultrasound and MRI.

In a sensitivity analysis, when looking at imaging from patients’ first visit across the study cohort, non-Hispanic Black children were significantly less likely to get imaging than non-Hispanic White children (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.79).

“This remained significant even after adjustment for a priori specified confounders including hospital propensity to image,” the authors write.

Authors acknowledge that it is possible that some of the differences may be attributable to the patient mix regarding severity of cases or indications for imaging by hospital, but they note that all models were adjusted for diagnosis-related group and other potential confounders.

This study did not assess whether one group is being overtested. Researchers also note that higher rates of imaging do not necessarily indicate higher quality of care.

However, the authors note, previous research has suggested overtesting of non-Hispanic White patients for head CT and chest pain, as well as patterns of overtreatment of non-Hispanic White patients who have bronchiolitis or viral upper respiratory tract infections.

Medell Briggs-Malonson, MD, MPH, chief of health equity, diversity and inclusion for the University of California, Los Angeles, Hospital and Clinic System, who was not part of the study, said in an interview “this all rings true.”

“This is not the first study we have had in either the pediatric or adult populations that shows disparate levels of care as well as health outcomes. Now we are starting to be able to measure it,” she said.

This study is further evidence of medical racism, she says, and highlights that it’s not the hospital choice or the insurance type affecting the numbers, she said.

“When you control for those factors, it looks to be it’s only due to race and that’s because of the very deep levels of implicit bias as well as explicit bias that we still have in our health systems and even in our providers,” said Dr. Briggs-Malonson, who is also an associate professor of emergency medicine at UCLA. “It’s incredibly important to identify and immediately address.”

What can be done?

Changing these patterns starts with knowing the numbers, the authors write.

“Hospitals should measure their own differences in imaging rates and increase awareness of existing areas of differential treatment as a starting point for improvement,” Dr. Samuels-Kalow and coauthors say.

Dr. Briggs-Malonson added that guidelines are very clear about when children should get imaging. Adhering to evidence-based guidelines can help avoid variations in care from external factors.

“If children are not receiving the absolute best comprehensive evaluation in the emergency department that they deserve, we can miss many different illnesses, which can lead to worse outcomes,” she noted.

As for what might motivate lack of imaging, Dr. Briggs-Malonson pointed to longstanding trends of providers thinking complaints raised by minority patients may not be as severe as they report. Conversely, in caring for White patients there may be a feeling that more tests and imaging may be better out of more fear of missing something, she said.

At UCLA, she says, dashboards have been developed to track statistics on care by age, race, ethnicity, language, insurance type, etc., though not specifically in pediatric imaging, to assess and address any care inequities.

Summer L. Kaplan, MD, MS, director of emergency radiology at Children’s Hospital of Philadelphia, who also was not part of the study, said the finding of racial disparities in pediatric ED imaging provides evidence that gaps still exist in providing the best care to all children and families seeking emergency care.

“However, it is important to recognize that more imaging does not equal better care,” she said. “More imaging may be associated with unnecessary, low-value tests that may add radiation and other risks but do not improve care.”

She said higher rates of imaging may occur when patients present early in the course of a disease, when the differential diagnosis remains broad.

If families have delayed seeking care because of time constraints, transportation problems, cost of care, or mistrust of the health system, children may present later in the course of a disease and require less imaging for a diagnosis, she explained.

“This paper offers a valuable look at the inequities that exist in pediatric emergency imaging use, and further research will be essential to understand and address the causes of these differences,” Dr. Kaplan said.

A coauthor reported compensation as a member of a Medical Review Committee for Highmark. Other coauthors reported grants from the U.S. Agency for Healthcare Research and Quality outside the submitted work. Dr. Briggs-Malonson and Dr. Kaplan reported no relevant financial relationships.

I suspect that you have heard or read about the recent study in the Journal of Neuroscience that claims to have discovered evidence that as children become teenagers, their brains begin to tune out their mother’s voices. The story appeared in at least 10 Internet news sources including the American Academy of Pediatrics’ daily briefing.

Based on functional MRI studies by a group at Stanford (Calif.) University, the researchers found that while in general, teenagers became more attentive to all voices as they reached puberty, novel voices were favored over the maternal voices that had flooded their environment as younger children. Of course none of this comes as a surprise to anyone who has parented a teenager or spent any time trying to communicate with adolescents. Although we all must be a bit careful not to put too much stock in functional MRI studies, these findings do suggest a physiologic basis for the peer pressure that becomes one of the hallmarks of adolescence. I wouldn’t be surprised if some clever entrepreneur has already begun using MRI to search for just the right tonal qualities that will make the perfect Internet influencer.

But, will these MRI studies help parents who have already thrown up their arms and admitted defeat mumbling, “He’s stopped listening to me?” The more observant parents already realized long ago that their words were often the least effective tools in their tool kit when it comes to modifying behavior.

Just listen in any neighborhood playground or grocery store to how often you hear a parent trying to get a toddler or young child to correct a misbehavior using threats or promises that you and everyone else within earshot knows will never be followed by any consequence. How often do you see a parent modeling behaviors that they expect their children to avoid?

Some more “enlightened” parents will avoid threats and instead attempt to engage in a dialogue with their misbehaving child hoping that a rational discussion with a sleep-deprived toddler in full tantrum mode can convince the youngster to self-correct.

I’m sure you learned and may have even used the playground retort “sticks and stones may break my bones but words will never hurt me.” Of course more untrue words were never spoken. Words can hurt and they can scar. But words and threats can also be hollow and will fall on ears deafened by months and years during which there were no consequences. It is certainly nice to know that there is some physiologic correlation to what we all suspected. The good news is that teenagers are still listening to us, although they are increasingly more interested in what their peers and the rest of the world has to say.

What the study fails to point out is that while teenagers may still be listening to us their behavior is molded not so much by what we say but how we as parents and adults behave. Have we parented in a way in which our words are followed up with appropriate consequences? And, more importantly, have we modeled behavior that matches our words? We need to help parents realize that words can be important but parenting by example is the gold standard.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I suspect that you have heard or read about the recent study in the Journal of Neuroscience that claims to have discovered evidence that as children become teenagers, their brains begin to tune out their mother’s voices. The story appeared in at least 10 Internet news sources including the American Academy of Pediatrics’ daily briefing.

Based on functional MRI studies by a group at Stanford (Calif.) University, the researchers found that while in general, teenagers became more attentive to all voices as they reached puberty, novel voices were favored over the maternal voices that had flooded their environment as younger children. Of course none of this comes as a surprise to anyone who has parented a teenager or spent any time trying to communicate with adolescents. Although we all must be a bit careful not to put too much stock in functional MRI studies, these findings do suggest a physiologic basis for the peer pressure that becomes one of the hallmarks of adolescence. I wouldn’t be surprised if some clever entrepreneur has already begun using MRI to search for just the right tonal qualities that will make the perfect Internet influencer.

But, will these MRI studies help parents who have already thrown up their arms and admitted defeat mumbling, “He’s stopped listening to me?” The more observant parents already realized long ago that their words were often the least effective tools in their tool kit when it comes to modifying behavior.

Just listen in any neighborhood playground or grocery store to how often you hear a parent trying to get a toddler or young child to correct a misbehavior using threats or promises that you and everyone else within earshot knows will never be followed by any consequence. How often do you see a parent modeling behaviors that they expect their children to avoid?

Some more “enlightened” parents will avoid threats and instead attempt to engage in a dialogue with their misbehaving child hoping that a rational discussion with a sleep-deprived toddler in full tantrum mode can convince the youngster to self-correct.

I’m sure you learned and may have even used the playground retort “sticks and stones may break my bones but words will never hurt me.” Of course more untrue words were never spoken. Words can hurt and they can scar. But words and threats can also be hollow and will fall on ears deafened by months and years during which there were no consequences. It is certainly nice to know that there is some physiologic correlation to what we all suspected. The good news is that teenagers are still listening to us, although they are increasingly more interested in what their peers and the rest of the world has to say.

What the study fails to point out is that while teenagers may still be listening to us their behavior is molded not so much by what we say but how we as parents and adults behave. Have we parented in a way in which our words are followed up with appropriate consequences? And, more importantly, have we modeled behavior that matches our words? We need to help parents realize that words can be important but parenting by example is the gold standard.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I suspect that you have heard or read about the recent study in the Journal of Neuroscience that claims to have discovered evidence that as children become teenagers, their brains begin to tune out their mother’s voices. The story appeared in at least 10 Internet news sources including the American Academy of Pediatrics’ daily briefing.

Based on functional MRI studies by a group at Stanford (Calif.) University, the researchers found that while in general, teenagers became more attentive to all voices as they reached puberty, novel voices were favored over the maternal voices that had flooded their environment as younger children. Of course none of this comes as a surprise to anyone who has parented a teenager or spent any time trying to communicate with adolescents. Although we all must be a bit careful not to put too much stock in functional MRI studies, these findings do suggest a physiologic basis for the peer pressure that becomes one of the hallmarks of adolescence. I wouldn’t be surprised if some clever entrepreneur has already begun using MRI to search for just the right tonal qualities that will make the perfect Internet influencer.

But, will these MRI studies help parents who have already thrown up their arms and admitted defeat mumbling, “He’s stopped listening to me?” The more observant parents already realized long ago that their words were often the least effective tools in their tool kit when it comes to modifying behavior.

Just listen in any neighborhood playground or grocery store to how often you hear a parent trying to get a toddler or young child to correct a misbehavior using threats or promises that you and everyone else within earshot knows will never be followed by any consequence. How often do you see a parent modeling behaviors that they expect their children to avoid?

Some more “enlightened” parents will avoid threats and instead attempt to engage in a dialogue with their misbehaving child hoping that a rational discussion with a sleep-deprived toddler in full tantrum mode can convince the youngster to self-correct.

I’m sure you learned and may have even used the playground retort “sticks and stones may break my bones but words will never hurt me.” Of course more untrue words were never spoken. Words can hurt and they can scar. But words and threats can also be hollow and will fall on ears deafened by months and years during which there were no consequences. It is certainly nice to know that there is some physiologic correlation to what we all suspected. The good news is that teenagers are still listening to us, although they are increasingly more interested in what their peers and the rest of the world has to say.

What the study fails to point out is that while teenagers may still be listening to us their behavior is molded not so much by what we say but how we as parents and adults behave. Have we parented in a way in which our words are followed up with appropriate consequences? And, more importantly, have we modeled behavior that matches our words? We need to help parents realize that words can be important but parenting by example is the gold standard.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Patients coinfected with hepatitis B virus (HBV) and human immunodeficiency virus who take tenofovir disoproxil fumarate (TDF) may have worsening renal function and bone turnover, according to a small, prospective cohort study in HIV Medicine.

“In this HBV-HIV cohort of adults with high prevalence of tenofovir use, several biomarkers of renal function and bone turnover indicated worsening status over approximately 4 years, highlighting the importance of clinicians’ awareness,” lead author Richard K. Sterling, MD, MSc, assistant chair of research in the department of internal medicine of Virginia Commonwealth University, Richmond, told this news organization in an email.

TDF is a common component of antiretroviral therapy (ART) in adults coinfected with HBV and HIV. The drug is known to adversely affect kidney function and bone turnover, but few studies have evaluated these issues, the authors write.

Dr. Sterling and colleagues enrolled adults coinfected with HBV and HIV who were taking any type of ART in their study at eight sites in North America.

The authors assessed demographics, medical history, current health status reports, physical exams, and blood and urine tests. They extracted clinical, laboratory, and radiologic data from medical records, and they processed whole blood, stored serum at -70 °C (-94 °F) at each site, and tested specimens in central laboratories.

The researchers assessed the participants at baseline and every 24 weeks for up to 192 weeks (3.7 years). They tested bone markers from stored serum at baseline, week 96, and week 192. And they recorded changes in renal function markers and bone turnover over time.

At baseline, the median age of the 115 patients was 49 years; 91% were male, and 52% were non-Hispanic Black. Their median body mass index was 26 kg/m², with 6.3% of participants underweight and 59% overweight or obese. The participants had been living with HIV for a median of about 20 years.

Overall, 84% of participants reported tenofovir use, 3% reported no HBV therapy, and 80% had HBV/HIV suppression. In addition, 13% had stage 2 liver fibrosis and 23% had stage 3 to 4 liver fibrosis. No participants reported using immunosuppressants, 4% reported using an anticoagulant, 3% reported taking calcium plus vitamin D, and 33% reported taking multivitamins.

Throughout the follow-up period, TDF use ranged from 80% to 92%. Estimated glomerular filtration rate (eGFR) dropped from 87.1 to 79.9 ml/min/1.73m² over 192 weeks (P < .001); but eGFR prevalence < 60 ml/min/1.73m² did not appear to change over time (always < 16%; P = .43).

From baseline to week 192, procollagen type 1 N-terminal propeptide (P1NP) dropped from 146.7 to 130.5 ng/ml (P = .001), osteocalcin dropped from 14.4 to 10.2 ng/ml (P < .001), and C-terminal telopeptides of type I collagen (CTX-1) dropped from 373 to 273 pg/ml (P < .001).

Predictors of decrease in eGFR included younger age, male sex, and overweight or obesity. Predictors of worsening bone turnover included Black race, healthy weight, advanced fibrosis, undetectable HBV DNA, and lower parathyroid hormone level.
 

Monitor patients with HBV and HIV closely

“The long-term effects of TDF on renal and bone health are important to monitor,” Dr. Sterling advised. “For renal health, physicians should monitor GFR as well as creatinine. For bone health, monitoring serum calcium, vitamin D, parathyroid hormone, and phosphate may not catch increased bone turnover.”

“We knew that TDF can cause renal dysfunction; however, we were surprised that we did not observe significant rise in serum creatinine but did observe decline in glomerular filtration rate and several markers of increased bone turnover,” he added.

Dr. Sterling acknowledged that limitations of the study include its small cohort, short follow-up, and lack of control participants who were taking TDF while mono-infected with either HBV or HIV. He added that strengths include close follow-up, use of bone turnover markers, and control for severity of liver disease.

Joseph Alvarnas, MD, a hematologist and oncologist in the department of hematology & hematopoietic cell transplant at City of Hope Comprehensive Cancer Center, Duarte, California, told this news organization that he welcomes the rigor of the study. “This study provides an important reminder of the complexities of taking a comprehensive management approach to the care of patients with long-term HIV infection,” Dr. Alvarnas wrote in an email. He was not involved in the study.

“More than 6 million people worldwide live with coinfection,” he added. “Patients coinfected with HBV and HIV have additional care needs over those living with only chronic HIV infection. With more HIV-infected patients becoming long-term survivors who are managed through the use of effective ART, fully understanding the differentiated long-term care needs of this population is important.”

Debika Bhattacharya, MD, a specialist in HIV and viral hepatitis coinfection in the Division of Infectious Diseases at UCLA Health, Los Angeles, joined Dr. Sterling and Dr. Alvarnas in advising clinicians to regularly evaluate the kidney and bone health of their coinfected patients.

“While this study focuses the very common antiretroviral agent TDF, it will be important to see the impact of a similar drug, tenofovir alafenamide (TAF) – which has been associated with less impact on bone and kidney health – on clinical outcomes in HBV-HIV coinfection,” Dr. Bhattacharya, who also was not involved in the study, wrote in an email.

The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Sterling has served on boards for Pfizer and AskBio, and he reports research grants from Gilead, Abbott, AbbVie, and Roche to his institution. Most other authors report financial relationships with pharmaceutical companies. Dr. Alvarnas reports no relevant financial relationships. Dr. Bhattacharya has received a research grant from Gilead Sciences, paid to her institution.

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

Patients coinfected with hepatitis B virus (HBV) and human immunodeficiency virus who take tenofovir disoproxil fumarate (TDF) may have worsening renal function and bone turnover, according to a small, prospective cohort study in HIV Medicine.

“In this HBV-HIV cohort of adults with high prevalence of tenofovir use, several biomarkers of renal function and bone turnover indicated worsening status over approximately 4 years, highlighting the importance of clinicians’ awareness,” lead author Richard K. Sterling, MD, MSc, assistant chair of research in the department of internal medicine of Virginia Commonwealth University, Richmond, told this news organization in an email.

TDF is a common component of antiretroviral therapy (ART) in adults coinfected with HBV and HIV. The drug is known to adversely affect kidney function and bone turnover, but few studies have evaluated these issues, the authors write.

Dr. Sterling and colleagues enrolled adults coinfected with HBV and HIV who were taking any type of ART in their study at eight sites in North America.

The authors assessed demographics, medical history, current health status reports, physical exams, and blood and urine tests. They extracted clinical, laboratory, and radiologic data from medical records, and they processed whole blood, stored serum at -70 °C (-94 °F) at each site, and tested specimens in central laboratories.

The researchers assessed the participants at baseline and every 24 weeks for up to 192 weeks (3.7 years). They tested bone markers from stored serum at baseline, week 96, and week 192. And they recorded changes in renal function markers and bone turnover over time.

At baseline, the median age of the 115 patients was 49 years; 91% were male, and 52% were non-Hispanic Black. Their median body mass index was 26 kg/m², with 6.3% of participants underweight and 59% overweight or obese. The participants had been living with HIV for a median of about 20 years.

Overall, 84% of participants reported tenofovir use, 3% reported no HBV therapy, and 80% had HBV/HIV suppression. In addition, 13% had stage 2 liver fibrosis and 23% had stage 3 to 4 liver fibrosis. No participants reported using immunosuppressants, 4% reported using an anticoagulant, 3% reported taking calcium plus vitamin D, and 33% reported taking multivitamins.

Throughout the follow-up period, TDF use ranged from 80% to 92%. Estimated glomerular filtration rate (eGFR) dropped from 87.1 to 79.9 ml/min/1.73m² over 192 weeks (P < .001); but eGFR prevalence < 60 ml/min/1.73m² did not appear to change over time (always < 16%; P = .43).

From baseline to week 192, procollagen type 1 N-terminal propeptide (P1NP) dropped from 146.7 to 130.5 ng/ml (P = .001), osteocalcin dropped from 14.4 to 10.2 ng/ml (P < .001), and C-terminal telopeptides of type I collagen (CTX-1) dropped from 373 to 273 pg/ml (P < .001).

Predictors of decrease in eGFR included younger age, male sex, and overweight or obesity. Predictors of worsening bone turnover included Black race, healthy weight, advanced fibrosis, undetectable HBV DNA, and lower parathyroid hormone level.
 

Monitor patients with HBV and HIV closely

“The long-term effects of TDF on renal and bone health are important to monitor,” Dr. Sterling advised. “For renal health, physicians should monitor GFR as well as creatinine. For bone health, monitoring serum calcium, vitamin D, parathyroid hormone, and phosphate may not catch increased bone turnover.”

“We knew that TDF can cause renal dysfunction; however, we were surprised that we did not observe significant rise in serum creatinine but did observe decline in glomerular filtration rate and several markers of increased bone turnover,” he added.

Dr. Sterling acknowledged that limitations of the study include its small cohort, short follow-up, and lack of control participants who were taking TDF while mono-infected with either HBV or HIV. He added that strengths include close follow-up, use of bone turnover markers, and control for severity of liver disease.

Joseph Alvarnas, MD, a hematologist and oncologist in the department of hematology & hematopoietic cell transplant at City of Hope Comprehensive Cancer Center, Duarte, California, told this news organization that he welcomes the rigor of the study. “This study provides an important reminder of the complexities of taking a comprehensive management approach to the care of patients with long-term HIV infection,” Dr. Alvarnas wrote in an email. He was not involved in the study.

“More than 6 million people worldwide live with coinfection,” he added. “Patients coinfected with HBV and HIV have additional care needs over those living with only chronic HIV infection. With more HIV-infected patients becoming long-term survivors who are managed through the use of effective ART, fully understanding the differentiated long-term care needs of this population is important.”

Debika Bhattacharya, MD, a specialist in HIV and viral hepatitis coinfection in the Division of Infectious Diseases at UCLA Health, Los Angeles, joined Dr. Sterling and Dr. Alvarnas in advising clinicians to regularly evaluate the kidney and bone health of their coinfected patients.

“While this study focuses the very common antiretroviral agent TDF, it will be important to see the impact of a similar drug, tenofovir alafenamide (TAF) – which has been associated with less impact on bone and kidney health – on clinical outcomes in HBV-HIV coinfection,” Dr. Bhattacharya, who also was not involved in the study, wrote in an email.

The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Sterling has served on boards for Pfizer and AskBio, and he reports research grants from Gilead, Abbott, AbbVie, and Roche to his institution. Most other authors report financial relationships with pharmaceutical companies. Dr. Alvarnas reports no relevant financial relationships. Dr. Bhattacharya has received a research grant from Gilead Sciences, paid to her institution.

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

Patients coinfected with hepatitis B virus (HBV) and human immunodeficiency virus who take tenofovir disoproxil fumarate (TDF) may have worsening renal function and bone turnover, according to a small, prospective cohort study in HIV Medicine.

“In this HBV-HIV cohort of adults with high prevalence of tenofovir use, several biomarkers of renal function and bone turnover indicated worsening status over approximately 4 years, highlighting the importance of clinicians’ awareness,” lead author Richard K. Sterling, MD, MSc, assistant chair of research in the department of internal medicine of Virginia Commonwealth University, Richmond, told this news organization in an email.

TDF is a common component of antiretroviral therapy (ART) in adults coinfected with HBV and HIV. The drug is known to adversely affect kidney function and bone turnover, but few studies have evaluated these issues, the authors write.

Dr. Sterling and colleagues enrolled adults coinfected with HBV and HIV who were taking any type of ART in their study at eight sites in North America.

The authors assessed demographics, medical history, current health status reports, physical exams, and blood and urine tests. They extracted clinical, laboratory, and radiologic data from medical records, and they processed whole blood, stored serum at -70 °C (-94 °F) at each site, and tested specimens in central laboratories.

The researchers assessed the participants at baseline and every 24 weeks for up to 192 weeks (3.7 years). They tested bone markers from stored serum at baseline, week 96, and week 192. And they recorded changes in renal function markers and bone turnover over time.

At baseline, the median age of the 115 patients was 49 years; 91% were male, and 52% were non-Hispanic Black. Their median body mass index was 26 kg/m², with 6.3% of participants underweight and 59% overweight or obese. The participants had been living with HIV for a median of about 20 years.

Overall, 84% of participants reported tenofovir use, 3% reported no HBV therapy, and 80% had HBV/HIV suppression. In addition, 13% had stage 2 liver fibrosis and 23% had stage 3 to 4 liver fibrosis. No participants reported using immunosuppressants, 4% reported using an anticoagulant, 3% reported taking calcium plus vitamin D, and 33% reported taking multivitamins.

Throughout the follow-up period, TDF use ranged from 80% to 92%. Estimated glomerular filtration rate (eGFR) dropped from 87.1 to 79.9 ml/min/1.73m² over 192 weeks (P < .001); but eGFR prevalence < 60 ml/min/1.73m² did not appear to change over time (always < 16%; P = .43).

From baseline to week 192, procollagen type 1 N-terminal propeptide (P1NP) dropped from 146.7 to 130.5 ng/ml (P = .001), osteocalcin dropped from 14.4 to 10.2 ng/ml (P < .001), and C-terminal telopeptides of type I collagen (CTX-1) dropped from 373 to 273 pg/ml (P < .001).

Predictors of decrease in eGFR included younger age, male sex, and overweight or obesity. Predictors of worsening bone turnover included Black race, healthy weight, advanced fibrosis, undetectable HBV DNA, and lower parathyroid hormone level.
 

Monitor patients with HBV and HIV closely

“The long-term effects of TDF on renal and bone health are important to monitor,” Dr. Sterling advised. “For renal health, physicians should monitor GFR as well as creatinine. For bone health, monitoring serum calcium, vitamin D, parathyroid hormone, and phosphate may not catch increased bone turnover.”

“We knew that TDF can cause renal dysfunction; however, we were surprised that we did not observe significant rise in serum creatinine but did observe decline in glomerular filtration rate and several markers of increased bone turnover,” he added.

Dr. Sterling acknowledged that limitations of the study include its small cohort, short follow-up, and lack of control participants who were taking TDF while mono-infected with either HBV or HIV. He added that strengths include close follow-up, use of bone turnover markers, and control for severity of liver disease.

Joseph Alvarnas, MD, a hematologist and oncologist in the department of hematology & hematopoietic cell transplant at City of Hope Comprehensive Cancer Center, Duarte, California, told this news organization that he welcomes the rigor of the study. “This study provides an important reminder of the complexities of taking a comprehensive management approach to the care of patients with long-term HIV infection,” Dr. Alvarnas wrote in an email. He was not involved in the study.

“More than 6 million people worldwide live with coinfection,” he added. “Patients coinfected with HBV and HIV have additional care needs over those living with only chronic HIV infection. With more HIV-infected patients becoming long-term survivors who are managed through the use of effective ART, fully understanding the differentiated long-term care needs of this population is important.”

Debika Bhattacharya, MD, a specialist in HIV and viral hepatitis coinfection in the Division of Infectious Diseases at UCLA Health, Los Angeles, joined Dr. Sterling and Dr. Alvarnas in advising clinicians to regularly evaluate the kidney and bone health of their coinfected patients.

“While this study focuses the very common antiretroviral agent TDF, it will be important to see the impact of a similar drug, tenofovir alafenamide (TAF) – which has been associated with less impact on bone and kidney health – on clinical outcomes in HBV-HIV coinfection,” Dr. Bhattacharya, who also was not involved in the study, wrote in an email.

The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Sterling has served on boards for Pfizer and AskBio, and he reports research grants from Gilead, Abbott, AbbVie, and Roche to his institution. Most other authors report financial relationships with pharmaceutical companies. Dr. Alvarnas reports no relevant financial relationships. Dr. Bhattacharya has received a research grant from Gilead Sciences, paid to her institution.

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

SAN DIEGO – Twelve years ago, Merete Haedersdal, MD, PhD, and colleagues published data from a swine study, which showed for the first time that the ablative fractional laser can be used to boost the uptake of drugs into the skin.

That discovery paved the way for what are now well-established clinical applications of laser-assisted drug delivery for treating actinic keratoses and scars. According to Dr. Haedersdal, professor of dermatology at the University of Copenhagen, evolving clinical indications for laser-assisted drug delivery include rejuvenation, local anesthesia, melasma, onychomycosis, hyperhidrosis, alopecia, and vitiligo, while emerging indications include treatment of skin cancer with PD-1 inhibitors and combination chemotherapy regimens, and vaccinations.

During a presentation at the annual conference of the American Society for Laser Medicine and Surgery, she said that researchers have much to learn about laser-assisted drug delivery, including biodistribution of the drug being delivered. Pointing out that so far, “what we have been dealing with is primarily looking at the skin as a black box,” she asked, “what happens when we drill the holes and drugs are applied on top of the skin and swim through the tiny channels?”

By using high-performance liquid chromatography (HPLC) and HPLC mass spectrometry to measure drug concentration in the skin, she and her colleagues have observed enhanced uptake of drugs – 4-fold to 40-fold greater – primarily in ex vivo pig skin. “We do know from ex vivo models that it’s much easier to boost the uptake in the skin” when compared with in vivo human use, where much lower drug concentrations are detected, said Dr. Haedersdal, who, along with Emily Wenande, MD, PhD, and R. Rox Anderson, MD, at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston, authored a clinical review, published in 2020, on the basics of laser-assisted drug delivery.

“What we are working on now is visualizing what’s taking place when we apply the holes and the drugs in the skin. This is the key to tailoring laser-assisted uptake to specific dermatologic diseases being treated,” she said. To date, she and her colleagues have examined the interaction with tissue using different devices, including ex vivo confocal microscopy, to view the thermal response to ablative fractional laser and radiofrequency. “We want to take that to the next level and look at the drug biodistribution.”

Efforts are underway to compare the pattern of drug distribution with different modes of delivery, such as comparing ablative fractional laser to intradermal needle injection. “We are also working on pneumatic jet injection, which creates a focal drug distribution,” said Dr. Haedersdal, who is a visiting scientist at the Wellman Center. “In the future, we may take advantage of device-tailored biodistribution, depending on which clinical indication we are treating.”

Another important aspect to consider is drug retention in the skin. In a study presented as an abstract at the meeting, led by Dr. Wenande, she, Dr. Haedersdal, and colleagues used a pig model to evaluate the effect of three vasoregulative interventions on ablative fractional laser-assisted 5-fluororacil concentrations in in vivo skin. The three interventions were brimonidine 0.33% solution, epinephrine 10 mcg/mL gel, and a 595-nm pulsed dye laser (PDL) in designated treatment areas.

“What we learned from that was in the short term – 1-4 hours – the ablative fractional laser enhanced the uptake of 5-FU, but it was very transient,” with a twofold increased concentration of 5-FU, Dr. Haedersdal said. Over 48-72 hours, after PDL, there was “sustained enhancement of drug in the skin by three to four times,” she noted.

The synergy of systemic drugs with ablative fractional laser therapy is also being evaluated. In a mouse study led by Dr. Haedersdal’s colleague, senior researcher Uffe H. Olesen, PhD, the treatment of advanced squamous cell carcinoma tumors with a combination of ablative fractional laser and systemic treatment with PD-1 inhibitors resulted in the clearance of more tumors than with either treatment as monotherapy. “What we want to explore is the laser-induced tumor immune response in keratinocyte cancers,” she added.

“When you shine the laser on the skin, there is a robust increase of neutrophilic granulocytes.” Combining this topical immune-boosting response with systemic delivery of PD-1 inhibitors in a mouse model with basal cell carcinoma, she said, “we learned that, when we compare systemic PD-1 inhibitors alone to the laser alone and then with combination therapy, there was an increased tumor clearance of basal cell carcinomas and also enhanced survival of the mice” with the combination, she said. There were also “enhanced neutrophilic counts and both CD4- and CD8-positive cells were increased,” she added.

Dr. Haedersdal disclosed that she has received grants or research funding from Lutronic, Venus Concept, Leo Pharma, and Mirai Medical.

SAN DIEGO – Twelve years ago, Merete Haedersdal, MD, PhD, and colleagues published data from a swine study, which showed for the first time that the ablative fractional laser can be used to boost the uptake of drugs into the skin.

That discovery paved the way for what are now well-established clinical applications of laser-assisted drug delivery for treating actinic keratoses and scars. According to Dr. Haedersdal, professor of dermatology at the University of Copenhagen, evolving clinical indications for laser-assisted drug delivery include rejuvenation, local anesthesia, melasma, onychomycosis, hyperhidrosis, alopecia, and vitiligo, while emerging indications include treatment of skin cancer with PD-1 inhibitors and combination chemotherapy regimens, and vaccinations.

During a presentation at the annual conference of the American Society for Laser Medicine and Surgery, she said that researchers have much to learn about laser-assisted drug delivery, including biodistribution of the drug being delivered. Pointing out that so far, “what we have been dealing with is primarily looking at the skin as a black box,” she asked, “what happens when we drill the holes and drugs are applied on top of the skin and swim through the tiny channels?”

By using high-performance liquid chromatography (HPLC) and HPLC mass spectrometry to measure drug concentration in the skin, she and her colleagues have observed enhanced uptake of drugs – 4-fold to 40-fold greater – primarily in ex vivo pig skin. “We do know from ex vivo models that it’s much easier to boost the uptake in the skin” when compared with in vivo human use, where much lower drug concentrations are detected, said Dr. Haedersdal, who, along with Emily Wenande, MD, PhD, and R. Rox Anderson, MD, at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston, authored a clinical review, published in 2020, on the basics of laser-assisted drug delivery.

“What we are working on now is visualizing what’s taking place when we apply the holes and the drugs in the skin. This is the key to tailoring laser-assisted uptake to specific dermatologic diseases being treated,” she said. To date, she and her colleagues have examined the interaction with tissue using different devices, including ex vivo confocal microscopy, to view the thermal response to ablative fractional laser and radiofrequency. “We want to take that to the next level and look at the drug biodistribution.”

Efforts are underway to compare the pattern of drug distribution with different modes of delivery, such as comparing ablative fractional laser to intradermal needle injection. “We are also working on pneumatic jet injection, which creates a focal drug distribution,” said Dr. Haedersdal, who is a visiting scientist at the Wellman Center. “In the future, we may take advantage of device-tailored biodistribution, depending on which clinical indication we are treating.”

Another important aspect to consider is drug retention in the skin. In a study presented as an abstract at the meeting, led by Dr. Wenande, she, Dr. Haedersdal, and colleagues used a pig model to evaluate the effect of three vasoregulative interventions on ablative fractional laser-assisted 5-fluororacil concentrations in in vivo skin. The three interventions were brimonidine 0.33% solution, epinephrine 10 mcg/mL gel, and a 595-nm pulsed dye laser (PDL) in designated treatment areas.

“What we learned from that was in the short term – 1-4 hours – the ablative fractional laser enhanced the uptake of 5-FU, but it was very transient,” with a twofold increased concentration of 5-FU, Dr. Haedersdal said. Over 48-72 hours, after PDL, there was “sustained enhancement of drug in the skin by three to four times,” she noted.

The synergy of systemic drugs with ablative fractional laser therapy is also being evaluated. In a mouse study led by Dr. Haedersdal’s colleague, senior researcher Uffe H. Olesen, PhD, the treatment of advanced squamous cell carcinoma tumors with a combination of ablative fractional laser and systemic treatment with PD-1 inhibitors resulted in the clearance of more tumors than with either treatment as monotherapy. “What we want to explore is the laser-induced tumor immune response in keratinocyte cancers,” she added.

“When you shine the laser on the skin, there is a robust increase of neutrophilic granulocytes.” Combining this topical immune-boosting response with systemic delivery of PD-1 inhibitors in a mouse model with basal cell carcinoma, she said, “we learned that, when we compare systemic PD-1 inhibitors alone to the laser alone and then with combination therapy, there was an increased tumor clearance of basal cell carcinomas and also enhanced survival of the mice” with the combination, she said. There were also “enhanced neutrophilic counts and both CD4- and CD8-positive cells were increased,” she added.

Dr. Haedersdal disclosed that she has received grants or research funding from Lutronic, Venus Concept, Leo Pharma, and Mirai Medical.

SAN DIEGO – Twelve years ago, Merete Haedersdal, MD, PhD, and colleagues published data from a swine study, which showed for the first time that the ablative fractional laser can be used to boost the uptake of drugs into the skin.

That discovery paved the way for what are now well-established clinical applications of laser-assisted drug delivery for treating actinic keratoses and scars. According to Dr. Haedersdal, professor of dermatology at the University of Copenhagen, evolving clinical indications for laser-assisted drug delivery include rejuvenation, local anesthesia, melasma, onychomycosis, hyperhidrosis, alopecia, and vitiligo, while emerging indications include treatment of skin cancer with PD-1 inhibitors and combination chemotherapy regimens, and vaccinations.

During a presentation at the annual conference of the American Society for Laser Medicine and Surgery, she said that researchers have much to learn about laser-assisted drug delivery, including biodistribution of the drug being delivered. Pointing out that so far, “what we have been dealing with is primarily looking at the skin as a black box,” she asked, “what happens when we drill the holes and drugs are applied on top of the skin and swim through the tiny channels?”

By using high-performance liquid chromatography (HPLC) and HPLC mass spectrometry to measure drug concentration in the skin, she and her colleagues have observed enhanced uptake of drugs – 4-fold to 40-fold greater – primarily in ex vivo pig skin. “We do know from ex vivo models that it’s much easier to boost the uptake in the skin” when compared with in vivo human use, where much lower drug concentrations are detected, said Dr. Haedersdal, who, along with Emily Wenande, MD, PhD, and R. Rox Anderson, MD, at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston, authored a clinical review, published in 2020, on the basics of laser-assisted drug delivery.

“What we are working on now is visualizing what’s taking place when we apply the holes and the drugs in the skin. This is the key to tailoring laser-assisted uptake to specific dermatologic diseases being treated,” she said. To date, she and her colleagues have examined the interaction with tissue using different devices, including ex vivo confocal microscopy, to view the thermal response to ablative fractional laser and radiofrequency. “We want to take that to the next level and look at the drug biodistribution.”

Efforts are underway to compare the pattern of drug distribution with different modes of delivery, such as comparing ablative fractional laser to intradermal needle injection. “We are also working on pneumatic jet injection, which creates a focal drug distribution,” said Dr. Haedersdal, who is a visiting scientist at the Wellman Center. “In the future, we may take advantage of device-tailored biodistribution, depending on which clinical indication we are treating.”

Another important aspect to consider is drug retention in the skin. In a study presented as an abstract at the meeting, led by Dr. Wenande, she, Dr. Haedersdal, and colleagues used a pig model to evaluate the effect of three vasoregulative interventions on ablative fractional laser-assisted 5-fluororacil concentrations in in vivo skin. The three interventions were brimonidine 0.33% solution, epinephrine 10 mcg/mL gel, and a 595-nm pulsed dye laser (PDL) in designated treatment areas.

“What we learned from that was in the short term – 1-4 hours – the ablative fractional laser enhanced the uptake of 5-FU, but it was very transient,” with a twofold increased concentration of 5-FU, Dr. Haedersdal said. Over 48-72 hours, after PDL, there was “sustained enhancement of drug in the skin by three to four times,” she noted.

The synergy of systemic drugs with ablative fractional laser therapy is also being evaluated. In a mouse study led by Dr. Haedersdal’s colleague, senior researcher Uffe H. Olesen, PhD, the treatment of advanced squamous cell carcinoma tumors with a combination of ablative fractional laser and systemic treatment with PD-1 inhibitors resulted in the clearance of more tumors than with either treatment as monotherapy. “What we want to explore is the laser-induced tumor immune response in keratinocyte cancers,” she added.

“When you shine the laser on the skin, there is a robust increase of neutrophilic granulocytes.” Combining this topical immune-boosting response with systemic delivery of PD-1 inhibitors in a mouse model with basal cell carcinoma, she said, “we learned that, when we compare systemic PD-1 inhibitors alone to the laser alone and then with combination therapy, there was an increased tumor clearance of basal cell carcinomas and also enhanced survival of the mice” with the combination, she said. There were also “enhanced neutrophilic counts and both CD4- and CD8-positive cells were increased,” she added.

Dr. Haedersdal disclosed that she has received grants or research funding from Lutronic, Venus Concept, Leo Pharma, and Mirai Medical.

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

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

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

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

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

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

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

The European Alliance of Associations for Rheumatology has updated its recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The 2022 revision – which was unveiled at the annual European Congress of Rheumatology – includes guidance on using new drugs, such as avacopan (Tavneos) and mepolizumab (Nucala), as well as revised recommendations on the use of rituximab and glucocorticosteroids.

EULAR

The overhaul also contains specific recommendations for treating eosinophilic granulomatosis with polyangiitis (EGPA), separating it out from granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for the first time.

“Until now, EGPA has usually been managed in the same way as [the] other diseases,” Bernhard Hellmich, MD, of the University of Tübingen (Germany) said in an interview ahead of his presentation at the congress.

“But we now have data on each type specifically, so there is good reason to make separate recommendations,” he added.

Indeed, so much new data has become available in the past few years there are only three recommendations that remain unchanged from the previous iteration published in 2016.

Since then, “several high-impact studies in AAV have been published and the results of these studies required an update of the existing recommendations,” Dr. Hellmich said.

Developed in record time – just 7 months from start to finish – the process of updating the recommendations on AAV followed EULAR’s standard operating procedures. An important step in this process is to perform a systemic literature review. Perhaps crucially, and in contrast to the first U.S. vasculitis guidelines published only in 2021, the most recent literature search was able to include data on avacopan, which was approved for use in Europe in January as an adjunctive treatment for adults with severe active GPA and MPA.

The results of the literature review were reported separately at the EULAR 2022 Congress, with separate presentations highlighting the data behind the amended treatment and diagnostic and follow-up procedure recommendations.
 

Highlights of the changes

A key change is the introduction of four overarching principles, which weren’t included in the previous update, said Dr. Hellmich.

“We moved some of the existing recommendations with low level of evidence to overarching principles,” he added, stating that the first general principle was that all patients should be offered “the best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety, and costs.”

The second principle states that patients should have access to education that covers the prognosis and impact of AAV, including recognizing warning symptoms and treatment options.

The third focuses on screening for adverse effects and comorbidities, recommending that patients are given appropriate prophylaxis and lifestyle advice.

Finally, the fourth general principle recognizes that AAV is a rare group of heterogenous and potentially life-threatening diseases that need multidisciplinary care, with access to specific vasculitis expertise.
 

New recommendations

Of the 17 recommendations made, 6 are completely new, including one on ANCA testing in patients who are suspected of having AAV.

“We recommend testing for both PR3- and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing,” Dr. Hellmich said. This is based on strong new evidence that antigen-specific assays have superior diagnostic accuracy, compared with indirect immunofluorescence.

“We also want to emphasize that ANCA testing should be done in patients with signs and symptoms in order to minimize the risk of false-positive results,” Dr. Hellmich said.

Also new is the recommendation to use oral steroids to induce remission in GPA/MPA, followed by a stepwise reduction in the dose, aiming for a dose of not more than 5 mg prednisolone per day by 4-5 months of treatment.

“Glucocorticoids are very effective, but also are the major trigger of infections in AAV,” said Dr. Hellmich. This is important since infections are a major driver of early mortality in AAV.

“Another possibility to reduce glucocorticoid exposure is avacopan,” he said. It’s recommended to be used in combination with rituximab or cyclophosphamide for remission induction in GPA/MPA as a strategy to basically “get rid of steroids.”

Indeed, “for patients who really have a high burden of glucocorticoid-associated adverse effects, especially relapsing patients, I think it would make sense just to give avacopan and no steroids,” Dr. Hellmich said.

Other new recommendations concern remission induction and maintenance therapy in new-onset EGPA. Regarding the latter, the choice of treatment depends on whether there is an organ- or life-threatening situation, with methotrexate, azathioprine, mepolizumab, or rituximab all recommended equally, or if there is no organ- or life-threatening situation, then mepolizumab is preferred.
 

Revised and unchanged recommendations

Eight of the recommendations have been revised, with rituximab being placed more prominently as a treatment in some. For remission induction in GPA and MPA with organ- or life threatening disease, rituximab is now the preferred option for relapsing disease. Rituximab also replaced methotrexate as the preferred option for maintaining remission, although methotrexate and azathioprine can still be considered as alternatives.

Another changed statement is on the duration of maintenance treatment in GPA and MPA, which now advocates 1-2 years of treatment after achieving remission. Longer therapy might be needed in relapsing cases, but the benefits and risks need to be carefully considered and patient preferences taken into account.

Prophylaxis against pneumonia and other infections is still recommended, with the revised guidance noting that patients receiving cyclophosphamide, rituximab, or high-dose steroids, should be treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

“There are retrospective data in the AAV population that the administration of co-trimoxazole reduces not only the incidence of pneumocystis, but also of other infections. So, this is important recommendation for clinical practice,” Dr. Hellmich said.
 

Summing up

“For a rare disease group, I think this is very good progress,” said Dr. Hellmich, but “there are still many open questions, so we have a long research agenda.”

There is purposefully no recommendation on COVID-19, however, as “the conditions that impact COVID outcomes change rapidly and any recommendation made now is likely to be outdated soon; the AAV recommendations are intended to last for at least a couple of years.”

In a press release issued by the German Society for Rheumatology, which was unrelated to Dr. Hellmich’s talk, experts commented on vasculitis guidelines generally, noting that there has been a move toward using biologic therapies such as rituximab and mepolizumab as a new standard of therapy.

DGRh President and chief physician at the Immanuel Hospital in Berlin Andreas Krause, MD, observed that “cyclophosphamide, which was used in the past and which inhibits blood formation in the bone marrow and can lead to infertility, can now often be dispensed with.”

Julia Holle, MD, of Rheumazentrum Schleswig-Holstein Mitte in Neumünster, Germany, was also quoted in the press release, saying that, “for patients, the successful use of biologics and the reduction in the glucocorticoid dose is important progress.”

Dr. Holle was involved in the development of revised European guidelines. She is also the lead author of a recent publication on treatment of vasculitis on available evidence. Dr. Hellmich acknowledged having ties to multiple pharma companies, acting as speaker, consultant, or both to Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, InflaRx, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Vifor.


 

The European Alliance of Associations for Rheumatology has updated its recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The 2022 revision – which was unveiled at the annual European Congress of Rheumatology – includes guidance on using new drugs, such as avacopan (Tavneos) and mepolizumab (Nucala), as well as revised recommendations on the use of rituximab and glucocorticosteroids.

EULAR

The overhaul also contains specific recommendations for treating eosinophilic granulomatosis with polyangiitis (EGPA), separating it out from granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for the first time.

“Until now, EGPA has usually been managed in the same way as [the] other diseases,” Bernhard Hellmich, MD, of the University of Tübingen (Germany) said in an interview ahead of his presentation at the congress.

“But we now have data on each type specifically, so there is good reason to make separate recommendations,” he added.

Indeed, so much new data has become available in the past few years there are only three recommendations that remain unchanged from the previous iteration published in 2016.

Since then, “several high-impact studies in AAV have been published and the results of these studies required an update of the existing recommendations,” Dr. Hellmich said.

Developed in record time – just 7 months from start to finish – the process of updating the recommendations on AAV followed EULAR’s standard operating procedures. An important step in this process is to perform a systemic literature review. Perhaps crucially, and in contrast to the first U.S. vasculitis guidelines published only in 2021, the most recent literature search was able to include data on avacopan, which was approved for use in Europe in January as an adjunctive treatment for adults with severe active GPA and MPA.

The results of the literature review were reported separately at the EULAR 2022 Congress, with separate presentations highlighting the data behind the amended treatment and diagnostic and follow-up procedure recommendations.
 

Highlights of the changes

A key change is the introduction of four overarching principles, which weren’t included in the previous update, said Dr. Hellmich.

“We moved some of the existing recommendations with low level of evidence to overarching principles,” he added, stating that the first general principle was that all patients should be offered “the best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety, and costs.”

The second principle states that patients should have access to education that covers the prognosis and impact of AAV, including recognizing warning symptoms and treatment options.

The third focuses on screening for adverse effects and comorbidities, recommending that patients are given appropriate prophylaxis and lifestyle advice.

Finally, the fourth general principle recognizes that AAV is a rare group of heterogenous and potentially life-threatening diseases that need multidisciplinary care, with access to specific vasculitis expertise.
 

New recommendations

Of the 17 recommendations made, 6 are completely new, including one on ANCA testing in patients who are suspected of having AAV.

“We recommend testing for both PR3- and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing,” Dr. Hellmich said. This is based on strong new evidence that antigen-specific assays have superior diagnostic accuracy, compared with indirect immunofluorescence.

“We also want to emphasize that ANCA testing should be done in patients with signs and symptoms in order to minimize the risk of false-positive results,” Dr. Hellmich said.

Also new is the recommendation to use oral steroids to induce remission in GPA/MPA, followed by a stepwise reduction in the dose, aiming for a dose of not more than 5 mg prednisolone per day by 4-5 months of treatment.

“Glucocorticoids are very effective, but also are the major trigger of infections in AAV,” said Dr. Hellmich. This is important since infections are a major driver of early mortality in AAV.

“Another possibility to reduce glucocorticoid exposure is avacopan,” he said. It’s recommended to be used in combination with rituximab or cyclophosphamide for remission induction in GPA/MPA as a strategy to basically “get rid of steroids.”

Indeed, “for patients who really have a high burden of glucocorticoid-associated adverse effects, especially relapsing patients, I think it would make sense just to give avacopan and no steroids,” Dr. Hellmich said.

Other new recommendations concern remission induction and maintenance therapy in new-onset EGPA. Regarding the latter, the choice of treatment depends on whether there is an organ- or life-threatening situation, with methotrexate, azathioprine, mepolizumab, or rituximab all recommended equally, or if there is no organ- or life-threatening situation, then mepolizumab is preferred.
 

Revised and unchanged recommendations

Eight of the recommendations have been revised, with rituximab being placed more prominently as a treatment in some. For remission induction in GPA and MPA with organ- or life threatening disease, rituximab is now the preferred option for relapsing disease. Rituximab also replaced methotrexate as the preferred option for maintaining remission, although methotrexate and azathioprine can still be considered as alternatives.

Another changed statement is on the duration of maintenance treatment in GPA and MPA, which now advocates 1-2 years of treatment after achieving remission. Longer therapy might be needed in relapsing cases, but the benefits and risks need to be carefully considered and patient preferences taken into account.

Prophylaxis against pneumonia and other infections is still recommended, with the revised guidance noting that patients receiving cyclophosphamide, rituximab, or high-dose steroids, should be treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

“There are retrospective data in the AAV population that the administration of co-trimoxazole reduces not only the incidence of pneumocystis, but also of other infections. So, this is important recommendation for clinical practice,” Dr. Hellmich said.
 

Summing up

“For a rare disease group, I think this is very good progress,” said Dr. Hellmich, but “there are still many open questions, so we have a long research agenda.”

There is purposefully no recommendation on COVID-19, however, as “the conditions that impact COVID outcomes change rapidly and any recommendation made now is likely to be outdated soon; the AAV recommendations are intended to last for at least a couple of years.”

In a press release issued by the German Society for Rheumatology, which was unrelated to Dr. Hellmich’s talk, experts commented on vasculitis guidelines generally, noting that there has been a move toward using biologic therapies such as rituximab and mepolizumab as a new standard of therapy.

DGRh President and chief physician at the Immanuel Hospital in Berlin Andreas Krause, MD, observed that “cyclophosphamide, which was used in the past and which inhibits blood formation in the bone marrow and can lead to infertility, can now often be dispensed with.”

Julia Holle, MD, of Rheumazentrum Schleswig-Holstein Mitte in Neumünster, Germany, was also quoted in the press release, saying that, “for patients, the successful use of biologics and the reduction in the glucocorticoid dose is important progress.”

Dr. Holle was involved in the development of revised European guidelines. She is also the lead author of a recent publication on treatment of vasculitis on available evidence. Dr. Hellmich acknowledged having ties to multiple pharma companies, acting as speaker, consultant, or both to Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, InflaRx, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Vifor.


 

The European Alliance of Associations for Rheumatology has updated its recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The 2022 revision – which was unveiled at the annual European Congress of Rheumatology – includes guidance on using new drugs, such as avacopan (Tavneos) and mepolizumab (Nucala), as well as revised recommendations on the use of rituximab and glucocorticosteroids.

EULAR

The overhaul also contains specific recommendations for treating eosinophilic granulomatosis with polyangiitis (EGPA), separating it out from granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for the first time.

“Until now, EGPA has usually been managed in the same way as [the] other diseases,” Bernhard Hellmich, MD, of the University of Tübingen (Germany) said in an interview ahead of his presentation at the congress.

“But we now have data on each type specifically, so there is good reason to make separate recommendations,” he added.

Indeed, so much new data has become available in the past few years there are only three recommendations that remain unchanged from the previous iteration published in 2016.

Since then, “several high-impact studies in AAV have been published and the results of these studies required an update of the existing recommendations,” Dr. Hellmich said.

Developed in record time – just 7 months from start to finish – the process of updating the recommendations on AAV followed EULAR’s standard operating procedures. An important step in this process is to perform a systemic literature review. Perhaps crucially, and in contrast to the first U.S. vasculitis guidelines published only in 2021, the most recent literature search was able to include data on avacopan, which was approved for use in Europe in January as an adjunctive treatment for adults with severe active GPA and MPA.

The results of the literature review were reported separately at the EULAR 2022 Congress, with separate presentations highlighting the data behind the amended treatment and diagnostic and follow-up procedure recommendations.
 

Highlights of the changes

A key change is the introduction of four overarching principles, which weren’t included in the previous update, said Dr. Hellmich.

“We moved some of the existing recommendations with low level of evidence to overarching principles,” he added, stating that the first general principle was that all patients should be offered “the best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety, and costs.”

The second principle states that patients should have access to education that covers the prognosis and impact of AAV, including recognizing warning symptoms and treatment options.

The third focuses on screening for adverse effects and comorbidities, recommending that patients are given appropriate prophylaxis and lifestyle advice.

Finally, the fourth general principle recognizes that AAV is a rare group of heterogenous and potentially life-threatening diseases that need multidisciplinary care, with access to specific vasculitis expertise.
 

New recommendations

Of the 17 recommendations made, 6 are completely new, including one on ANCA testing in patients who are suspected of having AAV.

“We recommend testing for both PR3- and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing,” Dr. Hellmich said. This is based on strong new evidence that antigen-specific assays have superior diagnostic accuracy, compared with indirect immunofluorescence.

“We also want to emphasize that ANCA testing should be done in patients with signs and symptoms in order to minimize the risk of false-positive results,” Dr. Hellmich said.

Also new is the recommendation to use oral steroids to induce remission in GPA/MPA, followed by a stepwise reduction in the dose, aiming for a dose of not more than 5 mg prednisolone per day by 4-5 months of treatment.

“Glucocorticoids are very effective, but also are the major trigger of infections in AAV,” said Dr. Hellmich. This is important since infections are a major driver of early mortality in AAV.

“Another possibility to reduce glucocorticoid exposure is avacopan,” he said. It’s recommended to be used in combination with rituximab or cyclophosphamide for remission induction in GPA/MPA as a strategy to basically “get rid of steroids.”

Indeed, “for patients who really have a high burden of glucocorticoid-associated adverse effects, especially relapsing patients, I think it would make sense just to give avacopan and no steroids,” Dr. Hellmich said.

Other new recommendations concern remission induction and maintenance therapy in new-onset EGPA. Regarding the latter, the choice of treatment depends on whether there is an organ- or life-threatening situation, with methotrexate, azathioprine, mepolizumab, or rituximab all recommended equally, or if there is no organ- or life-threatening situation, then mepolizumab is preferred.
 

Revised and unchanged recommendations

Eight of the recommendations have been revised, with rituximab being placed more prominently as a treatment in some. For remission induction in GPA and MPA with organ- or life threatening disease, rituximab is now the preferred option for relapsing disease. Rituximab also replaced methotrexate as the preferred option for maintaining remission, although methotrexate and azathioprine can still be considered as alternatives.

Another changed statement is on the duration of maintenance treatment in GPA and MPA, which now advocates 1-2 years of treatment after achieving remission. Longer therapy might be needed in relapsing cases, but the benefits and risks need to be carefully considered and patient preferences taken into account.

Prophylaxis against pneumonia and other infections is still recommended, with the revised guidance noting that patients receiving cyclophosphamide, rituximab, or high-dose steroids, should be treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

“There are retrospective data in the AAV population that the administration of co-trimoxazole reduces not only the incidence of pneumocystis, but also of other infections. So, this is important recommendation for clinical practice,” Dr. Hellmich said.
 

Summing up

“For a rare disease group, I think this is very good progress,” said Dr. Hellmich, but “there are still many open questions, so we have a long research agenda.”

There is purposefully no recommendation on COVID-19, however, as “the conditions that impact COVID outcomes change rapidly and any recommendation made now is likely to be outdated soon; the AAV recommendations are intended to last for at least a couple of years.”

In a press release issued by the German Society for Rheumatology, which was unrelated to Dr. Hellmich’s talk, experts commented on vasculitis guidelines generally, noting that there has been a move toward using biologic therapies such as rituximab and mepolizumab as a new standard of therapy.

DGRh President and chief physician at the Immanuel Hospital in Berlin Andreas Krause, MD, observed that “cyclophosphamide, which was used in the past and which inhibits blood formation in the bone marrow and can lead to infertility, can now often be dispensed with.”

Julia Holle, MD, of Rheumazentrum Schleswig-Holstein Mitte in Neumünster, Germany, was also quoted in the press release, saying that, “for patients, the successful use of biologics and the reduction in the glucocorticoid dose is important progress.”

Dr. Holle was involved in the development of revised European guidelines. She is also the lead author of a recent publication on treatment of vasculitis on available evidence. Dr. Hellmich acknowledged having ties to multiple pharma companies, acting as speaker, consultant, or both to Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, InflaRx, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Vifor.


 

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

Two doses of either the Pfizer-BioNTech COVID-19 vaccine or the Oxford AstraZeneca alternative provide equal and significant protection against severe disease in patients on hemodialysis who have contracted SARS-CoV-2 infection, results of a multicenter observational study indicate.

Following two doses of either vaccine, the risk of hospital admission was 75% lower among vaccinated patients while the risk of death was 88% lower, compared with those who remained unvaccinated.

No difference was seen between the two vaccine types in terms of outcome severity, and there was no loss of protection in patients over the age of 65 or with increasing time since vaccination, the authors add. The need for oxygen and ventilation was also halved among those who had received two shots, compared with those who had not.

“The coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on the CKD (chronic kidney disease) community, particularly for individuals receiving maintenance dialysis,” Matthew Oliver, MD, University of Toronto, and Peter Blake, MD, Western University, London, Ont., write in an editorial published with the study.

“Overall, [this and other studies] show that COVID-19 vaccination in the maintenance dialysis population provides moderate protection against acquiring SARS-CoV-2 infection but is highly protective against severe outcomes,” they conclude.

The study was published in the June issue of the Clinical Journal of the American Society of Nephrology.
 

Severe outcomes observed less in patients who tested positive

The cohort included 1,323 patients on hemodialysis who tested positive on PCR testing to SARS-CoV-2 during a surveillance interval between December 2020 and September 2021, report, Damien Ashby, MD, Hammersmith Hospital, London, and colleagues report.

Among those who tested positive, 79% had not been vaccinated, 7% tested positive after their first dose of either vaccine, and 14% tested positive at least 10 days beyond their second dose.

The course of illness was mild in 61% of patients in that they did not require hospital admission, investigators note. Oxygen support was required by 29% of those who tested positive, and 13% died before 28 days, they added. Among those who died within 28 days of testing positive, 90% of the deaths were deemed to be caused by the virus itself.

“Compared with unvaccinated patients, severe COVID-19 outcomes were observed less than half as often in patients testing positive for SARS-Co-V-2 at least 10 days after the second dose,” Dr. Ashby and colleagues emphasize.

“And the protection from severe illness associated with vaccination was most obvious in patients over 65 years, in whom severe COVID-19 outcomes were reduced at least as much after vaccination as in their younger peers,” they add. Following vaccination with the Pfizer-BioNTech vaccine, antibody levels in patients on dialysis were comparable with those of healthy controls.

In contrast, this was not the case for the Oxford AstraZeneca vaccine where neutralizing titers in patients who received the vaccine were less effective against most variants. Despite its ability to produce comparable immunogenicity, the Oxford AstraZeneca vaccine was clearly associated with clinical protection against severe illness, the authors stress.  

They also note that their results are relevant to vaccine uptake in the dialysis population where vaccine hesitancy remains a problem. “This study may, therefore, be useful in reducing vaccine hesitancy, which has resulted in low uptake in some countries (for example, Australia, where almost a quarter of patients on dialysis declined),” Dr. Ashby and colleagues point out.

Although significant vulnerability in the dialysis population remains, “this population has much to gain from vaccination, regardless of age or vaccine type,” the authors underscore.
 

CKD community quick to prioritize vaccine

As the editorialists point out, leaders in the CKD community were quick – and successful – in prioritizing vaccination in the dialysis population right from the beginning of the pandemic. For example, in Ontario, 90% of the maintenance dialysis population had received two doses of a COVID-19 vaccine by September 2021 and 78% had received three doses by January 2022.

Moreover, in Ontario, “our group found that two doses of mRNA vaccine reduced the risk of infection by 69%,” Dr. Oliver and Dr. Blake point out. U.S. researchers also found that the Pfizer mRNA vaccine reduced infection risk from COVID-19 by 79% while the Moderna mRNA vaccine reduced that risk by 73%. Vaccine effectiveness (VE) in the real-world setting indicates that COVID-19 vaccines provide moderate protection against being infected with the SARS-Co-V-2 virus, as the editorialists note.

However, “the VE for preventing severe outcomes is clinically more important for patients on dialysis because their risk of [morbid] events is high,” Dr. Oliver and Dr. Blake write. Indeed, their own study estimated that two doses of an mRNA vaccine reduced severe outcomes by 83%, “a greater benefit than for infection prevention,” they stress.

The editorialists caution that the SARS-CoV-2 virus continues to mutate and serology studies do show that vaccine-induced immunity does wane over time. Thus, while the COVID-19 pandemic is ever-changing, “we should conduct [VE] studies rigorously and expeditiously to bolster the case for prioritizing vaccination in the dialysis population,” Dr. Oliver and Dr. Blake recommend.
 

Need to increase vaccine acceptance

Commenting on the study, Uwe K.H. Korst from Bensheim, Germany, notes that COVID-19 is a daily reminder of how fragile life is for people with CKD. “Daily, the virus continues its horrific and unprecedented course through immunocompromised and immunosuppressed patients with kidney disease,” he writes.

Thus, Mr. Korst continues to call for additional education for health care professionals, patients, and the public to increase vaccine acceptance as well as more research to better understand the virus and its long-term consequences.

“Finally, patients need to express their needs, and physicians need to listen to patients’ voices,” Mr. Korst advises.

Dr. Oliver is a contracted medical lead of Ontario Renal Network and owner of Oliver Medical Management for which he holds patents and has received royalties. He has also reported receiving honoraria for speaking from Baxter Healthcare and participating in advisory boards for Amgen and Janssen. Dr. Blake has reported receiving honoraria from Baxter Global for speaking engagements and serves on the editorial board for the American Journal of Nephrology. Dr. Ashby and Dr. Korst have reported no relevant financial relationships.

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

Two doses of either the Pfizer-BioNTech COVID-19 vaccine or the Oxford AstraZeneca alternative provide equal and significant protection against severe disease in patients on hemodialysis who have contracted SARS-CoV-2 infection, results of a multicenter observational study indicate.

Following two doses of either vaccine, the risk of hospital admission was 75% lower among vaccinated patients while the risk of death was 88% lower, compared with those who remained unvaccinated.

No difference was seen between the two vaccine types in terms of outcome severity, and there was no loss of protection in patients over the age of 65 or with increasing time since vaccination, the authors add. The need for oxygen and ventilation was also halved among those who had received two shots, compared with those who had not.

“The coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on the CKD (chronic kidney disease) community, particularly for individuals receiving maintenance dialysis,” Matthew Oliver, MD, University of Toronto, and Peter Blake, MD, Western University, London, Ont., write in an editorial published with the study.

“Overall, [this and other studies] show that COVID-19 vaccination in the maintenance dialysis population provides moderate protection against acquiring SARS-CoV-2 infection but is highly protective against severe outcomes,” they conclude.

The study was published in the June issue of the Clinical Journal of the American Society of Nephrology.
 

Severe outcomes observed less in patients who tested positive

The cohort included 1,323 patients on hemodialysis who tested positive on PCR testing to SARS-CoV-2 during a surveillance interval between December 2020 and September 2021, report, Damien Ashby, MD, Hammersmith Hospital, London, and colleagues report.

Among those who tested positive, 79% had not been vaccinated, 7% tested positive after their first dose of either vaccine, and 14% tested positive at least 10 days beyond their second dose.

The course of illness was mild in 61% of patients in that they did not require hospital admission, investigators note. Oxygen support was required by 29% of those who tested positive, and 13% died before 28 days, they added. Among those who died within 28 days of testing positive, 90% of the deaths were deemed to be caused by the virus itself.

“Compared with unvaccinated patients, severe COVID-19 outcomes were observed less than half as often in patients testing positive for SARS-Co-V-2 at least 10 days after the second dose,” Dr. Ashby and colleagues emphasize.

“And the protection from severe illness associated with vaccination was most obvious in patients over 65 years, in whom severe COVID-19 outcomes were reduced at least as much after vaccination as in their younger peers,” they add. Following vaccination with the Pfizer-BioNTech vaccine, antibody levels in patients on dialysis were comparable with those of healthy controls.

In contrast, this was not the case for the Oxford AstraZeneca vaccine where neutralizing titers in patients who received the vaccine were less effective against most variants. Despite its ability to produce comparable immunogenicity, the Oxford AstraZeneca vaccine was clearly associated with clinical protection against severe illness, the authors stress.  

They also note that their results are relevant to vaccine uptake in the dialysis population where vaccine hesitancy remains a problem. “This study may, therefore, be useful in reducing vaccine hesitancy, which has resulted in low uptake in some countries (for example, Australia, where almost a quarter of patients on dialysis declined),” Dr. Ashby and colleagues point out.

Although significant vulnerability in the dialysis population remains, “this population has much to gain from vaccination, regardless of age or vaccine type,” the authors underscore.
 

CKD community quick to prioritize vaccine

As the editorialists point out, leaders in the CKD community were quick – and successful – in prioritizing vaccination in the dialysis population right from the beginning of the pandemic. For example, in Ontario, 90% of the maintenance dialysis population had received two doses of a COVID-19 vaccine by September 2021 and 78% had received three doses by January 2022.

Moreover, in Ontario, “our group found that two doses of mRNA vaccine reduced the risk of infection by 69%,” Dr. Oliver and Dr. Blake point out. U.S. researchers also found that the Pfizer mRNA vaccine reduced infection risk from COVID-19 by 79% while the Moderna mRNA vaccine reduced that risk by 73%. Vaccine effectiveness (VE) in the real-world setting indicates that COVID-19 vaccines provide moderate protection against being infected with the SARS-Co-V-2 virus, as the editorialists note.

However, “the VE for preventing severe outcomes is clinically more important for patients on dialysis because their risk of [morbid] events is high,” Dr. Oliver and Dr. Blake write. Indeed, their own study estimated that two doses of an mRNA vaccine reduced severe outcomes by 83%, “a greater benefit than for infection prevention,” they stress.

The editorialists caution that the SARS-CoV-2 virus continues to mutate and serology studies do show that vaccine-induced immunity does wane over time. Thus, while the COVID-19 pandemic is ever-changing, “we should conduct [VE] studies rigorously and expeditiously to bolster the case for prioritizing vaccination in the dialysis population,” Dr. Oliver and Dr. Blake recommend.
 

Need to increase vaccine acceptance

Commenting on the study, Uwe K.H. Korst from Bensheim, Germany, notes that COVID-19 is a daily reminder of how fragile life is for people with CKD. “Daily, the virus continues its horrific and unprecedented course through immunocompromised and immunosuppressed patients with kidney disease,” he writes.

Thus, Mr. Korst continues to call for additional education for health care professionals, patients, and the public to increase vaccine acceptance as well as more research to better understand the virus and its long-term consequences.

“Finally, patients need to express their needs, and physicians need to listen to patients’ voices,” Mr. Korst advises.

Dr. Oliver is a contracted medical lead of Ontario Renal Network and owner of Oliver Medical Management for which he holds patents and has received royalties. He has also reported receiving honoraria for speaking from Baxter Healthcare and participating in advisory boards for Amgen and Janssen. Dr. Blake has reported receiving honoraria from Baxter Global for speaking engagements and serves on the editorial board for the American Journal of Nephrology. Dr. Ashby and Dr. Korst have reported no relevant financial relationships.

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

Two doses of either the Pfizer-BioNTech COVID-19 vaccine or the Oxford AstraZeneca alternative provide equal and significant protection against severe disease in patients on hemodialysis who have contracted SARS-CoV-2 infection, results of a multicenter observational study indicate.

Following two doses of either vaccine, the risk of hospital admission was 75% lower among vaccinated patients while the risk of death was 88% lower, compared with those who remained unvaccinated.

No difference was seen between the two vaccine types in terms of outcome severity, and there was no loss of protection in patients over the age of 65 or with increasing time since vaccination, the authors add. The need for oxygen and ventilation was also halved among those who had received two shots, compared with those who had not.

“The coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on the CKD (chronic kidney disease) community, particularly for individuals receiving maintenance dialysis,” Matthew Oliver, MD, University of Toronto, and Peter Blake, MD, Western University, London, Ont., write in an editorial published with the study.

“Overall, [this and other studies] show that COVID-19 vaccination in the maintenance dialysis population provides moderate protection against acquiring SARS-CoV-2 infection but is highly protective against severe outcomes,” they conclude.

The study was published in the June issue of the Clinical Journal of the American Society of Nephrology.
 

Severe outcomes observed less in patients who tested positive

The cohort included 1,323 patients on hemodialysis who tested positive on PCR testing to SARS-CoV-2 during a surveillance interval between December 2020 and September 2021, report, Damien Ashby, MD, Hammersmith Hospital, London, and colleagues report.

Among those who tested positive, 79% had not been vaccinated, 7% tested positive after their first dose of either vaccine, and 14% tested positive at least 10 days beyond their second dose.

The course of illness was mild in 61% of patients in that they did not require hospital admission, investigators note. Oxygen support was required by 29% of those who tested positive, and 13% died before 28 days, they added. Among those who died within 28 days of testing positive, 90% of the deaths were deemed to be caused by the virus itself.

“Compared with unvaccinated patients, severe COVID-19 outcomes were observed less than half as often in patients testing positive for SARS-Co-V-2 at least 10 days after the second dose,” Dr. Ashby and colleagues emphasize.

“And the protection from severe illness associated with vaccination was most obvious in patients over 65 years, in whom severe COVID-19 outcomes were reduced at least as much after vaccination as in their younger peers,” they add. Following vaccination with the Pfizer-BioNTech vaccine, antibody levels in patients on dialysis were comparable with those of healthy controls.

In contrast, this was not the case for the Oxford AstraZeneca vaccine where neutralizing titers in patients who received the vaccine were less effective against most variants. Despite its ability to produce comparable immunogenicity, the Oxford AstraZeneca vaccine was clearly associated with clinical protection against severe illness, the authors stress.  

They also note that their results are relevant to vaccine uptake in the dialysis population where vaccine hesitancy remains a problem. “This study may, therefore, be useful in reducing vaccine hesitancy, which has resulted in low uptake in some countries (for example, Australia, where almost a quarter of patients on dialysis declined),” Dr. Ashby and colleagues point out.

Although significant vulnerability in the dialysis population remains, “this population has much to gain from vaccination, regardless of age or vaccine type,” the authors underscore.
 

CKD community quick to prioritize vaccine

As the editorialists point out, leaders in the CKD community were quick – and successful – in prioritizing vaccination in the dialysis population right from the beginning of the pandemic. For example, in Ontario, 90% of the maintenance dialysis population had received two doses of a COVID-19 vaccine by September 2021 and 78% had received three doses by January 2022.

Moreover, in Ontario, “our group found that two doses of mRNA vaccine reduced the risk of infection by 69%,” Dr. Oliver and Dr. Blake point out. U.S. researchers also found that the Pfizer mRNA vaccine reduced infection risk from COVID-19 by 79% while the Moderna mRNA vaccine reduced that risk by 73%. Vaccine effectiveness (VE) in the real-world setting indicates that COVID-19 vaccines provide moderate protection against being infected with the SARS-Co-V-2 virus, as the editorialists note.

However, “the VE for preventing severe outcomes is clinically more important for patients on dialysis because their risk of [morbid] events is high,” Dr. Oliver and Dr. Blake write. Indeed, their own study estimated that two doses of an mRNA vaccine reduced severe outcomes by 83%, “a greater benefit than for infection prevention,” they stress.

The editorialists caution that the SARS-CoV-2 virus continues to mutate and serology studies do show that vaccine-induced immunity does wane over time. Thus, while the COVID-19 pandemic is ever-changing, “we should conduct [VE] studies rigorously and expeditiously to bolster the case for prioritizing vaccination in the dialysis population,” Dr. Oliver and Dr. Blake recommend.
 

Need to increase vaccine acceptance

Commenting on the study, Uwe K.H. Korst from Bensheim, Germany, notes that COVID-19 is a daily reminder of how fragile life is for people with CKD. “Daily, the virus continues its horrific and unprecedented course through immunocompromised and immunosuppressed patients with kidney disease,” he writes.

Thus, Mr. Korst continues to call for additional education for health care professionals, patients, and the public to increase vaccine acceptance as well as more research to better understand the virus and its long-term consequences.

“Finally, patients need to express their needs, and physicians need to listen to patients’ voices,” Mr. Korst advises.

Dr. Oliver is a contracted medical lead of Ontario Renal Network and owner of Oliver Medical Management for which he holds patents and has received royalties. He has also reported receiving honoraria for speaking from Baxter Healthcare and participating in advisory boards for Amgen and Janssen. Dr. Blake has reported receiving honoraria from Baxter Global for speaking engagements and serves on the editorial board for the American Journal of Nephrology. Dr. Ashby and Dr. Korst have reported no relevant financial relationships.

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