Patients with multisystem inflammatory syndrome caused by COVID-19 typically seem to avoid coronary artery dilation early on, but they may be prone to cardiac injury and dysfunction longer term that requires a more discerning diagnostic approach to sort out.

The findings were revealed in a study of 28 children with COVID-19–related multisystem inflammatory syndrome (MIS-C) at Children’s Hospital of Philadelphia. The study reported that cardiac injury and dysfunction are common in these patients – even those who have preserved ejection fraction – and that diastolic dysfunction is persistent. For comparison, the study also included 20 healthy controls and 20 patients with classic Kawasaki disease (KD).

The study analyzed echocardiography findings in the patients, reporting left ventricular (LV) systolic and diastolic function were worse than in classic Kawasaki disease (KD), which MIS-C mimics. Lead author Daisuke Matsubara, MD, PhD, and colleagues reported that four markers – LV global longitudinal strain, LV circumferential strain rate, right ventricular strain, and left atrial strain – were the strongest predictors of myocardial injury in these patients. After the acute phase, systolic function tended to recover, but diastolic dysfunction persisted.
 

‘Strain’ measurement boosts accuracy

While echocardiography has been reported to be valuable in evaluating coronary artery function in MIS-C patients, Dr. Matsubara of the division of cardiology at CHOP, said in an interview that study is the first to use the newer echocardiography indexes, known as “strain,” to assess heart function.

“Strain is a more sensitive tool than more conventional indexes and can detect subtle decrease in heart function, even when ejection fraction is preserved,” he said. “Numerous publications have reached conclusions that strain improves the prognostic and diagnostic accuracy of echocardiography in a wide variety of cardiac pathologies causing LV dysfunction.”

Dr. Matsubara noted that the coronary arteries were mostly unaffected in the acute stage of MIS-C, as only one patient in their MIS-C cohort had coronary artery involvement, which normalized during early follow-up. “On the other hand, 20% of our classic KD patients had coronary abnormalities, including two with aneurysms.”

By using positive troponin I or elevated brain natriuretic peptide (BNP) to assess cardiac injury, they found a “high” (60%) incidence of myocardial injury in their MIS-C cohort. During early follow-up, most of the MIS-C patients showed normalization of systolic function, although diastolic dysfunction persisted.

When compared with the classic KD group, MIS-C patients had higher rates of mitral regurgitation (46% vs. 15%, P = .06), more pericardial effusion (32% vs. 15%, P = 0.46), and more pleural effusion (39% vs. 0%, P = .004). MIS-C patients with suspected myocardial injury show these findings more frequently than those with actual myocardial injury.

Compared with the healthy controls, the MIS-C patients showed both LV systolic and diastolic dysfunction as well as significantly lower left atrium (LA) strain and peak right ventricle (RV) free-wall longitudinal strain.

“In addition to the left ventricle, two other chambers of the heart, the LA and the RV that are often labeled as the ‘forgotten chambers’ of the heart, were also affected by MIS-C,” Dr. Matsubara said. “Both LA and RV strains were markedly reduced in MIS-C patients, compared to normal and KD patients.”

The study also indicates that elevated troponin I levels may not be as dire in children as they are in adults. Dr. Matsubara cited a study of more than 2,700 adult COVID-19 patients that found that even mild increases in troponin I level were associated with increased death during hospitalization (J Am Coll Cardiol. 2020;76:533-46).

However, most of the patients in the CHOP study, even those with elevated troponin I levels, recovered systolic function quickly. “We speculate that the elevation in cardiac troponins may have less dire implications in children, likely due to a more transient type of cardiac injury and less comorbidities in children,” he said. “Clearly further studies are needed before a definitive statement can be made.”

Dr. Matsubara added that recovered COVID-19 patients may be able to participate in sports as some schools reopen. “We are not saying restrict sport participation, but we are merely urging caution.”

Comprehensive LV evaluation needed

The findings reinforce that myocardial involvement is more frequent and sometimes more severe in MIS-C than previously thought, said Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital. “We are underestimating it by using just traditional measures like ejection fraction. It requires a comprehensive evaluation of left ventricular function; it really affects all aspects of the ventricle, both the systolic function and the diastolic function.”

This study supports that MIS-C patients should have a more detailed analysis than EF on echocardiography, including strain imaging. “Probably these patients should all be followed at centers where they can evaluate a more detailed analysis of the LV and RV function,” he said. Patients with ongoing CA enlargement and LV dysfunction should have follow-up cardiac care indefinitely. Patients who have no cardiac symptoms during the acute phase probably don’t need long-term follow-up.

“We’re just trying to learn more about this disease, and it’s certainly concerning that so many kids are having cardiac involvement,” Dr. Friedman said. “Fortunately they’re getting better; we’re just trying to find out what this means for the long term.”

Dr. Matsubara and Dr. Friedman have no relevant financial disclosures.

SOURCE: Matsubara D et al. J Am Coll Cardiol. 2020 Sep 2. doi: 10.1016/j.jacc.2020.08.056.

Patients with multisystem inflammatory syndrome caused by COVID-19 typically seem to avoid coronary artery dilation early on, but they may be prone to cardiac injury and dysfunction longer term that requires a more discerning diagnostic approach to sort out.

The findings were revealed in a study of 28 children with COVID-19–related multisystem inflammatory syndrome (MIS-C) at Children’s Hospital of Philadelphia. The study reported that cardiac injury and dysfunction are common in these patients – even those who have preserved ejection fraction – and that diastolic dysfunction is persistent. For comparison, the study also included 20 healthy controls and 20 patients with classic Kawasaki disease (KD).

The study analyzed echocardiography findings in the patients, reporting left ventricular (LV) systolic and diastolic function were worse than in classic Kawasaki disease (KD), which MIS-C mimics. Lead author Daisuke Matsubara, MD, PhD, and colleagues reported that four markers – LV global longitudinal strain, LV circumferential strain rate, right ventricular strain, and left atrial strain – were the strongest predictors of myocardial injury in these patients. After the acute phase, systolic function tended to recover, but diastolic dysfunction persisted.
 

‘Strain’ measurement boosts accuracy

While echocardiography has been reported to be valuable in evaluating coronary artery function in MIS-C patients, Dr. Matsubara of the division of cardiology at CHOP, said in an interview that study is the first to use the newer echocardiography indexes, known as “strain,” to assess heart function.

“Strain is a more sensitive tool than more conventional indexes and can detect subtle decrease in heart function, even when ejection fraction is preserved,” he said. “Numerous publications have reached conclusions that strain improves the prognostic and diagnostic accuracy of echocardiography in a wide variety of cardiac pathologies causing LV dysfunction.”

Dr. Matsubara noted that the coronary arteries were mostly unaffected in the acute stage of MIS-C, as only one patient in their MIS-C cohort had coronary artery involvement, which normalized during early follow-up. “On the other hand, 20% of our classic KD patients had coronary abnormalities, including two with aneurysms.”

By using positive troponin I or elevated brain natriuretic peptide (BNP) to assess cardiac injury, they found a “high” (60%) incidence of myocardial injury in their MIS-C cohort. During early follow-up, most of the MIS-C patients showed normalization of systolic function, although diastolic dysfunction persisted.

When compared with the classic KD group, MIS-C patients had higher rates of mitral regurgitation (46% vs. 15%, P = .06), more pericardial effusion (32% vs. 15%, P = 0.46), and more pleural effusion (39% vs. 0%, P = .004). MIS-C patients with suspected myocardial injury show these findings more frequently than those with actual myocardial injury.

Compared with the healthy controls, the MIS-C patients showed both LV systolic and diastolic dysfunction as well as significantly lower left atrium (LA) strain and peak right ventricle (RV) free-wall longitudinal strain.

“In addition to the left ventricle, two other chambers of the heart, the LA and the RV that are often labeled as the ‘forgotten chambers’ of the heart, were also affected by MIS-C,” Dr. Matsubara said. “Both LA and RV strains were markedly reduced in MIS-C patients, compared to normal and KD patients.”

The study also indicates that elevated troponin I levels may not be as dire in children as they are in adults. Dr. Matsubara cited a study of more than 2,700 adult COVID-19 patients that found that even mild increases in troponin I level were associated with increased death during hospitalization (J Am Coll Cardiol. 2020;76:533-46).

However, most of the patients in the CHOP study, even those with elevated troponin I levels, recovered systolic function quickly. “We speculate that the elevation in cardiac troponins may have less dire implications in children, likely due to a more transient type of cardiac injury and less comorbidities in children,” he said. “Clearly further studies are needed before a definitive statement can be made.”

Dr. Matsubara added that recovered COVID-19 patients may be able to participate in sports as some schools reopen. “We are not saying restrict sport participation, but we are merely urging caution.”

Comprehensive LV evaluation needed

The findings reinforce that myocardial involvement is more frequent and sometimes more severe in MIS-C than previously thought, said Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital. “We are underestimating it by using just traditional measures like ejection fraction. It requires a comprehensive evaluation of left ventricular function; it really affects all aspects of the ventricle, both the systolic function and the diastolic function.”

This study supports that MIS-C patients should have a more detailed analysis than EF on echocardiography, including strain imaging. “Probably these patients should all be followed at centers where they can evaluate a more detailed analysis of the LV and RV function,” he said. Patients with ongoing CA enlargement and LV dysfunction should have follow-up cardiac care indefinitely. Patients who have no cardiac symptoms during the acute phase probably don’t need long-term follow-up.

“We’re just trying to learn more about this disease, and it’s certainly concerning that so many kids are having cardiac involvement,” Dr. Friedman said. “Fortunately they’re getting better; we’re just trying to find out what this means for the long term.”

Dr. Matsubara and Dr. Friedman have no relevant financial disclosures.

SOURCE: Matsubara D et al. J Am Coll Cardiol. 2020 Sep 2. doi: 10.1016/j.jacc.2020.08.056.

Patients with multisystem inflammatory syndrome caused by COVID-19 typically seem to avoid coronary artery dilation early on, but they may be prone to cardiac injury and dysfunction longer term that requires a more discerning diagnostic approach to sort out.

The findings were revealed in a study of 28 children with COVID-19–related multisystem inflammatory syndrome (MIS-C) at Children’s Hospital of Philadelphia. The study reported that cardiac injury and dysfunction are common in these patients – even those who have preserved ejection fraction – and that diastolic dysfunction is persistent. For comparison, the study also included 20 healthy controls and 20 patients with classic Kawasaki disease (KD).

The study analyzed echocardiography findings in the patients, reporting left ventricular (LV) systolic and diastolic function were worse than in classic Kawasaki disease (KD), which MIS-C mimics. Lead author Daisuke Matsubara, MD, PhD, and colleagues reported that four markers – LV global longitudinal strain, LV circumferential strain rate, right ventricular strain, and left atrial strain – were the strongest predictors of myocardial injury in these patients. After the acute phase, systolic function tended to recover, but diastolic dysfunction persisted.
 

‘Strain’ measurement boosts accuracy

While echocardiography has been reported to be valuable in evaluating coronary artery function in MIS-C patients, Dr. Matsubara of the division of cardiology at CHOP, said in an interview that study is the first to use the newer echocardiography indexes, known as “strain,” to assess heart function.

“Strain is a more sensitive tool than more conventional indexes and can detect subtle decrease in heart function, even when ejection fraction is preserved,” he said. “Numerous publications have reached conclusions that strain improves the prognostic and diagnostic accuracy of echocardiography in a wide variety of cardiac pathologies causing LV dysfunction.”

Dr. Matsubara noted that the coronary arteries were mostly unaffected in the acute stage of MIS-C, as only one patient in their MIS-C cohort had coronary artery involvement, which normalized during early follow-up. “On the other hand, 20% of our classic KD patients had coronary abnormalities, including two with aneurysms.”

By using positive troponin I or elevated brain natriuretic peptide (BNP) to assess cardiac injury, they found a “high” (60%) incidence of myocardial injury in their MIS-C cohort. During early follow-up, most of the MIS-C patients showed normalization of systolic function, although diastolic dysfunction persisted.

When compared with the classic KD group, MIS-C patients had higher rates of mitral regurgitation (46% vs. 15%, P = .06), more pericardial effusion (32% vs. 15%, P = 0.46), and more pleural effusion (39% vs. 0%, P = .004). MIS-C patients with suspected myocardial injury show these findings more frequently than those with actual myocardial injury.

Compared with the healthy controls, the MIS-C patients showed both LV systolic and diastolic dysfunction as well as significantly lower left atrium (LA) strain and peak right ventricle (RV) free-wall longitudinal strain.

“In addition to the left ventricle, two other chambers of the heart, the LA and the RV that are often labeled as the ‘forgotten chambers’ of the heart, were also affected by MIS-C,” Dr. Matsubara said. “Both LA and RV strains were markedly reduced in MIS-C patients, compared to normal and KD patients.”

The study also indicates that elevated troponin I levels may not be as dire in children as they are in adults. Dr. Matsubara cited a study of more than 2,700 adult COVID-19 patients that found that even mild increases in troponin I level were associated with increased death during hospitalization (J Am Coll Cardiol. 2020;76:533-46).

However, most of the patients in the CHOP study, even those with elevated troponin I levels, recovered systolic function quickly. “We speculate that the elevation in cardiac troponins may have less dire implications in children, likely due to a more transient type of cardiac injury and less comorbidities in children,” he said. “Clearly further studies are needed before a definitive statement can be made.”

Dr. Matsubara added that recovered COVID-19 patients may be able to participate in sports as some schools reopen. “We are not saying restrict sport participation, but we are merely urging caution.”

Comprehensive LV evaluation needed

The findings reinforce that myocardial involvement is more frequent and sometimes more severe in MIS-C than previously thought, said Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital. “We are underestimating it by using just traditional measures like ejection fraction. It requires a comprehensive evaluation of left ventricular function; it really affects all aspects of the ventricle, both the systolic function and the diastolic function.”

This study supports that MIS-C patients should have a more detailed analysis than EF on echocardiography, including strain imaging. “Probably these patients should all be followed at centers where they can evaluate a more detailed analysis of the LV and RV function,” he said. Patients with ongoing CA enlargement and LV dysfunction should have follow-up cardiac care indefinitely. Patients who have no cardiac symptoms during the acute phase probably don’t need long-term follow-up.

“We’re just trying to learn more about this disease, and it’s certainly concerning that so many kids are having cardiac involvement,” Dr. Friedman said. “Fortunately they’re getting better; we’re just trying to find out what this means for the long term.”

Dr. Matsubara and Dr. Friedman have no relevant financial disclosures.

SOURCE: Matsubara D et al. J Am Coll Cardiol. 2020 Sep 2. doi: 10.1016/j.jacc.2020.08.056.

The immune system overactivation known as a “cytokine storm” does not play a major role in more severe COVID-19 outcomes, according to unexpected findings in new research. The findings stand in direct contrast to many previous reports.

“We were indeed surprised by the results of our study,” senior study author Peter Pickkers, MD, PhD, said in an interview.

In a unique approach, Dr. Pickkers and colleagues compared cytokine levels in critically ill people with COVID-19 with those in patients with bacterial sepsis, trauma, and after cardiac arrest.

“For the first time, we measured the cytokines in different diseases using the same methods. Our results convincingly show that the circulating cytokine concentrations are not higher, but lower, compared to other diseases,” said Dr. Pickkers, who is affiliated with the department of intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.

The team’s research was published online on Sept. 3 in a letter in JAMA.
 

Cytokines lower than expected

Normally, cytokines trigger inflammation and promote healing after trauma, infection, or other conditions.

Although a cytokine storm remains ill defined, the authors noted, many researchers have implicated a hyperinflammatory response involving these small proteins in the pathophysiology of COVID-19.

The question remains, however, whether all cytokine storms strike people with different conditions the same way.

Dr. Pickkers, lead author Matthijs Kox, PhD, and colleagues studied 46 people with COVID-19 and acute respiratory distress syndrome (ARDS) who were admitted to the ICU at Radboud University Medical Center. All participants underwent mechanical ventilation and were treated between March 11 and April 27, 2020.

The investigators measured plasma levels of cytokines, including tumor necrosis factor (TNF), interleukin-6, and IL-8. They compared results in this group with those in 51 patients who experienced septic shock and ARDS, 15 patients with septic shock without ARDS, 30 people with out-of-hospital cardiac arrest, and 62 people who experienced multiple traumas. They used historical data for the non–COVID-19 cohorts.
 

Conditional findings

Compared with patients with septic shock and ARDS, the COVID-19 cohort had lower levels of TNF, IL-6, and IL-8. The differences were statistically significant for TNF (P < .01), as well as for IL-6 and IL-8 concentrations (for both, P < .001).

In addition, the COVID-19 group had significantly lower IL-6 and IL-8 concentrations compared with the patients who had septic shock without ARDS.

The researchers likewise found lower concentrations of IL-8 in patients with COVID-19, compared with the out-of-hospital cardiac arrest patients. IL-8 levels did not differ between the COVID-19 and trauma groups.

Furthermore, the researchers found no differences in IL-6 concentrations between patients with COVID-19 and those who experienced out-of-hospital cardiac arrest or trauma.

However, levels of TNF in people with COVID-19 were higher than in trauma patients.

The small sample sizes and single-center study design are limitations.

“The findings of this preliminary analysis suggest COVID-19 may not be characterized by cytokine storm,” the researchers noted. However, they added, “whether anticytokine therapies will benefit patients with COVID-19 remains to be determined.”

Going forward, Dr. Pickkers and colleagues are investigating the effectiveness of different treatments to lower cytokine levels. They are treating people with COVID-19, for example, with the IL-1 cytokine inhibitor anakinra and steroids.

They also plan to assess the long-term effects of COVID-19 on the immune system. “Following an infection, it is known that the immune system may be suppressed for a longer period of time, and we are determining to what extent this is also present in COVID-19 patients,” Dr. Pickkers said.
 

Enough to cause a storm?

The study “is quite interesting, and data in this paper are consistent with our data,” Tadamitsu Kishimoto, MD, PhD, of the department of immune regulation at the Immunology Frontier Research Center at Osaka (Japan) University, said in an interview.

His study, published online August 21 in PNAS, also revealed lower serum IL-6 levels among people with COVID-19, compared with patients with bacterial ARDS or sepsis.

Dr. Kishimoto drew a distinction, however: COVID-19 patients can develop severe respiratory failure, suggesting a distinct immune reaction, compared with patients with bacterial sepsis. SARS-CoV-2 directly infects and activates endothelial cells rather than macrophages, as occurs in sepsis.

For this reason, Dr. Kishimoto said, “SARS-CoV-2 infection causes critical illness and severe dysfunction in respiratory organs and induces a cytokine storm,” even in the setting of lower but still elevated serum IL-6 levels.

Dr. Pickkers and Dr. Kishimoto reported no relevant financial relationships.

This story first appeared on Medscape.com.

The immune system overactivation known as a “cytokine storm” does not play a major role in more severe COVID-19 outcomes, according to unexpected findings in new research. The findings stand in direct contrast to many previous reports.

“We were indeed surprised by the results of our study,” senior study author Peter Pickkers, MD, PhD, said in an interview.

In a unique approach, Dr. Pickkers and colleagues compared cytokine levels in critically ill people with COVID-19 with those in patients with bacterial sepsis, trauma, and after cardiac arrest.

“For the first time, we measured the cytokines in different diseases using the same methods. Our results convincingly show that the circulating cytokine concentrations are not higher, but lower, compared to other diseases,” said Dr. Pickkers, who is affiliated with the department of intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.

The team’s research was published online on Sept. 3 in a letter in JAMA.
 

Cytokines lower than expected

Normally, cytokines trigger inflammation and promote healing after trauma, infection, or other conditions.

Although a cytokine storm remains ill defined, the authors noted, many researchers have implicated a hyperinflammatory response involving these small proteins in the pathophysiology of COVID-19.

The question remains, however, whether all cytokine storms strike people with different conditions the same way.

Dr. Pickkers, lead author Matthijs Kox, PhD, and colleagues studied 46 people with COVID-19 and acute respiratory distress syndrome (ARDS) who were admitted to the ICU at Radboud University Medical Center. All participants underwent mechanical ventilation and were treated between March 11 and April 27, 2020.

The investigators measured plasma levels of cytokines, including tumor necrosis factor (TNF), interleukin-6, and IL-8. They compared results in this group with those in 51 patients who experienced septic shock and ARDS, 15 patients with septic shock without ARDS, 30 people with out-of-hospital cardiac arrest, and 62 people who experienced multiple traumas. They used historical data for the non–COVID-19 cohorts.
 

Conditional findings

Compared with patients with septic shock and ARDS, the COVID-19 cohort had lower levels of TNF, IL-6, and IL-8. The differences were statistically significant for TNF (P < .01), as well as for IL-6 and IL-8 concentrations (for both, P < .001).

In addition, the COVID-19 group had significantly lower IL-6 and IL-8 concentrations compared with the patients who had septic shock without ARDS.

The researchers likewise found lower concentrations of IL-8 in patients with COVID-19, compared with the out-of-hospital cardiac arrest patients. IL-8 levels did not differ between the COVID-19 and trauma groups.

Furthermore, the researchers found no differences in IL-6 concentrations between patients with COVID-19 and those who experienced out-of-hospital cardiac arrest or trauma.

However, levels of TNF in people with COVID-19 were higher than in trauma patients.

The small sample sizes and single-center study design are limitations.

“The findings of this preliminary analysis suggest COVID-19 may not be characterized by cytokine storm,” the researchers noted. However, they added, “whether anticytokine therapies will benefit patients with COVID-19 remains to be determined.”

Going forward, Dr. Pickkers and colleagues are investigating the effectiveness of different treatments to lower cytokine levels. They are treating people with COVID-19, for example, with the IL-1 cytokine inhibitor anakinra and steroids.

They also plan to assess the long-term effects of COVID-19 on the immune system. “Following an infection, it is known that the immune system may be suppressed for a longer period of time, and we are determining to what extent this is also present in COVID-19 patients,” Dr. Pickkers said.
 

Enough to cause a storm?

The study “is quite interesting, and data in this paper are consistent with our data,” Tadamitsu Kishimoto, MD, PhD, of the department of immune regulation at the Immunology Frontier Research Center at Osaka (Japan) University, said in an interview.

His study, published online August 21 in PNAS, also revealed lower serum IL-6 levels among people with COVID-19, compared with patients with bacterial ARDS or sepsis.

Dr. Kishimoto drew a distinction, however: COVID-19 patients can develop severe respiratory failure, suggesting a distinct immune reaction, compared with patients with bacterial sepsis. SARS-CoV-2 directly infects and activates endothelial cells rather than macrophages, as occurs in sepsis.

For this reason, Dr. Kishimoto said, “SARS-CoV-2 infection causes critical illness and severe dysfunction in respiratory organs and induces a cytokine storm,” even in the setting of lower but still elevated serum IL-6 levels.

Dr. Pickkers and Dr. Kishimoto reported no relevant financial relationships.

This story first appeared on Medscape.com.

The immune system overactivation known as a “cytokine storm” does not play a major role in more severe COVID-19 outcomes, according to unexpected findings in new research. The findings stand in direct contrast to many previous reports.

“We were indeed surprised by the results of our study,” senior study author Peter Pickkers, MD, PhD, said in an interview.

In a unique approach, Dr. Pickkers and colleagues compared cytokine levels in critically ill people with COVID-19 with those in patients with bacterial sepsis, trauma, and after cardiac arrest.

“For the first time, we measured the cytokines in different diseases using the same methods. Our results convincingly show that the circulating cytokine concentrations are not higher, but lower, compared to other diseases,” said Dr. Pickkers, who is affiliated with the department of intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.

The team’s research was published online on Sept. 3 in a letter in JAMA.
 

Cytokines lower than expected

Normally, cytokines trigger inflammation and promote healing after trauma, infection, or other conditions.

Although a cytokine storm remains ill defined, the authors noted, many researchers have implicated a hyperinflammatory response involving these small proteins in the pathophysiology of COVID-19.

The question remains, however, whether all cytokine storms strike people with different conditions the same way.

Dr. Pickkers, lead author Matthijs Kox, PhD, and colleagues studied 46 people with COVID-19 and acute respiratory distress syndrome (ARDS) who were admitted to the ICU at Radboud University Medical Center. All participants underwent mechanical ventilation and were treated between March 11 and April 27, 2020.

The investigators measured plasma levels of cytokines, including tumor necrosis factor (TNF), interleukin-6, and IL-8. They compared results in this group with those in 51 patients who experienced septic shock and ARDS, 15 patients with septic shock without ARDS, 30 people with out-of-hospital cardiac arrest, and 62 people who experienced multiple traumas. They used historical data for the non–COVID-19 cohorts.
 

Conditional findings

Compared with patients with septic shock and ARDS, the COVID-19 cohort had lower levels of TNF, IL-6, and IL-8. The differences were statistically significant for TNF (P < .01), as well as for IL-6 and IL-8 concentrations (for both, P < .001).

In addition, the COVID-19 group had significantly lower IL-6 and IL-8 concentrations compared with the patients who had septic shock without ARDS.

The researchers likewise found lower concentrations of IL-8 in patients with COVID-19, compared with the out-of-hospital cardiac arrest patients. IL-8 levels did not differ between the COVID-19 and trauma groups.

Furthermore, the researchers found no differences in IL-6 concentrations between patients with COVID-19 and those who experienced out-of-hospital cardiac arrest or trauma.

However, levels of TNF in people with COVID-19 were higher than in trauma patients.

The small sample sizes and single-center study design are limitations.

“The findings of this preliminary analysis suggest COVID-19 may not be characterized by cytokine storm,” the researchers noted. However, they added, “whether anticytokine therapies will benefit patients with COVID-19 remains to be determined.”

Going forward, Dr. Pickkers and colleagues are investigating the effectiveness of different treatments to lower cytokine levels. They are treating people with COVID-19, for example, with the IL-1 cytokine inhibitor anakinra and steroids.

They also plan to assess the long-term effects of COVID-19 on the immune system. “Following an infection, it is known that the immune system may be suppressed for a longer period of time, and we are determining to what extent this is also present in COVID-19 patients,” Dr. Pickkers said.
 

Enough to cause a storm?

The study “is quite interesting, and data in this paper are consistent with our data,” Tadamitsu Kishimoto, MD, PhD, of the department of immune regulation at the Immunology Frontier Research Center at Osaka (Japan) University, said in an interview.

His study, published online August 21 in PNAS, also revealed lower serum IL-6 levels among people with COVID-19, compared with patients with bacterial ARDS or sepsis.

Dr. Kishimoto drew a distinction, however: COVID-19 patients can develop severe respiratory failure, suggesting a distinct immune reaction, compared with patients with bacterial sepsis. SARS-CoV-2 directly infects and activates endothelial cells rather than macrophages, as occurs in sepsis.

For this reason, Dr. Kishimoto said, “SARS-CoV-2 infection causes critical illness and severe dysfunction in respiratory organs and induces a cytokine storm,” even in the setting of lower but still elevated serum IL-6 levels.

Dr. Pickkers and Dr. Kishimoto reported no relevant financial relationships.

This story first appeared on Medscape.com.

HM20 Virtual session title

Call Me Maybe: Balancing Resident Autonomy with Sensible Supervision

Presenter

Daniel Steinberg, MD, SFHM, FACP

Session summary

In this session, Dr. Steinberg, professor of medicine and medical education, associate chair for education, and residency program director in the department of medicine at Icahn School of Medicine at Mount Sinai, New York, presented key factors, techniques, and approaches to supervising residents. He discussed the important balance of resident autonomy and supervision, especially since attendings need to focus on learner education along with patient care and safety.

Dr. Steinberg stated that resident supervision is driven by three factors: what residents need, what residents want, and what the supervisor can provide. Although data is mixed on whether supervision improves patient outcomes, supervision is essential for patient care and resident education. Dr. Steinberg showcased several relevant medical education studies relating to supervision and focused on a key question: Do you trust the resident?

The review of medical education literature discussed the meaning and development of trust, oral case presentations to determine trust, and the influence of supervisor experience. One study looked at the attendings’ remote access of EMR, which allows for remote supervision as a great way to determine trust of the resident. Another study showed that attendings want more communication than what residents provide and that the saying “Page me if you need me” does not encourage communication from residents as much as attendings would desire.
 

Key takeaways

• Resident supervision is driven by what residents need, what residents want, and what the supervisor can provide.
• Trust can be determined from direct supervision, oral presentations, and remote access of EMR, but it is also influenced by attending experience and style.
• To increase resident communication with the attending, do not say “Page me if you need me.” Instead, an attending should specifically state when a call to an attending is required.

Dr. Tantoco is an academic med-peds hospitalist practicing at Northwestern Memorial Hospital in Chicago and Ann & Robert H. Lurie Children’s Hospital of Chicago. She is an instructor of medicine (hospital medicine) and pediatrics at Northwestern University, also in Chicago.

HM20 Virtual session title

Call Me Maybe: Balancing Resident Autonomy with Sensible Supervision

Presenter

Daniel Steinberg, MD, SFHM, FACP

Session summary

In this session, Dr. Steinberg, professor of medicine and medical education, associate chair for education, and residency program director in the department of medicine at Icahn School of Medicine at Mount Sinai, New York, presented key factors, techniques, and approaches to supervising residents. He discussed the important balance of resident autonomy and supervision, especially since attendings need to focus on learner education along with patient care and safety.

Dr. Steinberg stated that resident supervision is driven by three factors: what residents need, what residents want, and what the supervisor can provide. Although data is mixed on whether supervision improves patient outcomes, supervision is essential for patient care and resident education. Dr. Steinberg showcased several relevant medical education studies relating to supervision and focused on a key question: Do you trust the resident?

The review of medical education literature discussed the meaning and development of trust, oral case presentations to determine trust, and the influence of supervisor experience. One study looked at the attendings’ remote access of EMR, which allows for remote supervision as a great way to determine trust of the resident. Another study showed that attendings want more communication than what residents provide and that the saying “Page me if you need me” does not encourage communication from residents as much as attendings would desire.
 

Key takeaways

• Resident supervision is driven by what residents need, what residents want, and what the supervisor can provide.
• Trust can be determined from direct supervision, oral presentations, and remote access of EMR, but it is also influenced by attending experience and style.
• To increase resident communication with the attending, do not say “Page me if you need me.” Instead, an attending should specifically state when a call to an attending is required.

Dr. Tantoco is an academic med-peds hospitalist practicing at Northwestern Memorial Hospital in Chicago and Ann & Robert H. Lurie Children’s Hospital of Chicago. She is an instructor of medicine (hospital medicine) and pediatrics at Northwestern University, also in Chicago.

HM20 Virtual session title

Call Me Maybe: Balancing Resident Autonomy with Sensible Supervision

Presenter

Daniel Steinberg, MD, SFHM, FACP

Session summary

In this session, Dr. Steinberg, professor of medicine and medical education, associate chair for education, and residency program director in the department of medicine at Icahn School of Medicine at Mount Sinai, New York, presented key factors, techniques, and approaches to supervising residents. He discussed the important balance of resident autonomy and supervision, especially since attendings need to focus on learner education along with patient care and safety.

Dr. Steinberg stated that resident supervision is driven by three factors: what residents need, what residents want, and what the supervisor can provide. Although data is mixed on whether supervision improves patient outcomes, supervision is essential for patient care and resident education. Dr. Steinberg showcased several relevant medical education studies relating to supervision and focused on a key question: Do you trust the resident?

The review of medical education literature discussed the meaning and development of trust, oral case presentations to determine trust, and the influence of supervisor experience. One study looked at the attendings’ remote access of EMR, which allows for remote supervision as a great way to determine trust of the resident. Another study showed that attendings want more communication than what residents provide and that the saying “Page me if you need me” does not encourage communication from residents as much as attendings would desire.
 

Key takeaways

• Resident supervision is driven by what residents need, what residents want, and what the supervisor can provide.
• Trust can be determined from direct supervision, oral presentations, and remote access of EMR, but it is also influenced by attending experience and style.
• To increase resident communication with the attending, do not say “Page me if you need me.” Instead, an attending should specifically state when a call to an attending is required.

Dr. Tantoco is an academic med-peds hospitalist practicing at Northwestern Memorial Hospital in Chicago and Ann & Robert H. Lurie Children’s Hospital of Chicago. She is an instructor of medicine (hospital medicine) and pediatrics at Northwestern University, also in Chicago.

Twelve U.S. states have now passed laws aimed at making insulin more affordable – and more than 30 are considering such legislation – but they all have gaps that still put the cost of this basic and essential medication out of reach for many with diabetes.

The laws only apply to health insurance through state-regulated plans, and not to the majority of health plans that cover most Americans: Medicare, Medicaid, the Veterans Affairs health system, or self-funded employer-sponsored plans.

Overall, Hannah Crabtree, an activist who writes the blog Data for Insulin, estimates state laws that limit copays, deductibles, or other out-of-pocket costs for insulin cover an average of 27% of people with diabetes across the United States.

And while diabetes activists have applauded state actions, most want more help for the under- and uninsured.

“Our chapter will be fighting harder next legislative session for the uninsured,” said Mindie Hooley, the leader of the Utah #insulin4all chapter, which successfully lobbied legislators to pass a bill signed by the state’s governor on March 30.

“With so many losing their jobs because of the pandemic, there’s no better time than now to fight for these patients who don’t have insurance,” Ms. Hooley said in an interview.

The American Diabetes Association has also been lobbying for state caps as one of many avenues for making insulin more affordable, said Stephen Habbe, the ADA’s director for state government affairs.

One in four insulin users report rationing the medication, Mr. Habbe said.

The state laws “can really provide important relief in terms of affordability for their insulin costs, which we know can be critical in terms of preserving their life and helping to prevent complications that can potentially be disabling or even deadly,” he said in an interview.

Activists with T1 International, which created the #insulin4all campaign, are working nationwide to convince state legislators to back measures that limit out-of-pocket costs for insulin, or for other diabetes medications and supplies.

Colorado, Connecticut, Delaware, Illinois, Maine, New Hampshire, New Mexico, New York, Utah, Virginia, Washington, and West Virginia have enacted such limits, with caps ranging from $25 to $100.
 

Insulin makers unfazed, blame insurers, PBMs for high prices

The three insulin manufacturers in the United States – Eli Lilly, Novo Nordisk, and Sanofi– have not overtly fought against the laws, although in July, the Pharmaceutical Research and Manufacturers of America did sue to block a related Minnesota law that provides a free emergency supply of insulin.

And the nonprofit news organization FairWarning reported in August that a lobbyist from Eli Lilly had attempted to push a Tennessee legislator to keep the uninsured from being eligible for any out-of-pocket limits.

The insulin makers have also not lowered prices in response to the mounting number of state laws.

They see no need, said Tara O’Neill Hayes, director of human welfare policy at the American Action Forum, a center right–leaning Washington, D.C., think tank.

“You’re going to do what you can get away with,” Ms. O’Neill Hayes said in an interview. “To the extent that they can keep their prices high and people are still buying, they have limited incentives to lower those costs.”

The insulin market is dysfunctional, she added. “The increasing cost of insulin seems primarily to be the result of a lack of competition in the market and convoluted drug pricing and insurance practices,” Ms. O’Neill Hayes and colleagues wrote in a report in April on federal and state attempts to address insulin affordability.

Novo Nordisk, however, maintains that drugmakers are not solely to blame.

“Everyone in the health care system has a role to play in affordability,” said Ken Inchausti, Novo Nordisk’s senior director for corporate communications. State legislation “attempts to address a systemic issue in [U.S.] health care: How benefit design can make medicines unaffordable for many, especially for those in high-deductible health plans,” he said in an interview.

“Efforts to place copay caps on insurance plans covering insulin can certainly help lower out-of-pocket costs,” said Mr. Inchausti.

Sanofi spokesperson Jon Florio said the company supports actions that increase affordable access to insulin. However, “while we support capped copays, we feel this should not be limited to just one class of medicines,” he said. Mr. Florio also noted that Sanofi provides out-of-pocket caps to anyone with commercial insurance and that anyone without insurance can buy one or multiple Sanofi insulins for a fixed price of $99 per month, up to 10 boxes of pens and/or 10-mL vials.

And Sanofi will take part in the Centers for Medicare & Medicaid Services’ new insulin demonstration program. Starting in 2021, CMS will cap insulin copays at $35 for people in Part D plans that participate.

Eli Lilly spokesperson Brad Jacklin said the company “believes in the common goal of ensuring affordable access to insulin and other life-saving medicines because nobody should have to forgo or ration because of cost.”

Lilly supports efforts “that more directly affect patients’ cost-sharing based on their health care coverage,” he said. Insurers and pharmacy benefit managers (PBMs) should pass savings on to patients, Mr. Jacklin urged. Lilly caps some insulins at $35 for the uninsured or commercially insured. The company will also participate in the CMS program.

Meanwhile, a PhRMA-sponsored website www.letstalkaboutcost.org said that, because they do not share savings, insurers and PBMs are responsible for high insulin costs.

Manufacturer assistance programs for patients with diabetes and other chronic diseases, on the other hand, can save individuals $300-$500 a year, PhRMA said in August.
 

PBMs point back at insulin manufacturers

PBMs, however, point back at drug companies. “PBMs have been able to moderate insulin costs for most consumers with insurance,” said J.C. Scott, president and CEO of the Pharmaceutical Care Management Association, the PBM trade group, in a statement.

The rising cost of insulin is caused by a lack of competition and overuse of patent extensions, PCMA maintains.

Health insurers, which, in tandem with PBMs, give insulins formulary preference based on a discounted price, are most likely to feel the impact of laws limiting out-of-pocket costs.

If they have to make up the shortfall from a patient’s reduced payment for a prescription, they will likely raise premiums, said Ms. O’Neill Hayes.

And if patients pay the same price for insulin – regardless of who makes it – drugmakers won’t have much incentive to offer discounts or rebates for formulary placement, she said. Again, that would likely lead to higher premiums.

David Allen, a spokesperson for America’s Health Insurance Plans, said in an interview that AHIP believes lack of competition has driven up insulin prices.

“High prices for insulin correspond with high health insurance costs for insulin,” he said. When CMS starts requiring drugmakers to discount their insulins for Medicare that will allow “health plans to use those savings to reduce out-of-pocket [costs] for seniors.”

He did not respond to a question as to why health insurers were not already passing savings on to commercially insured patients, especially in states with out-of-pocket limits.

Mr. Allen did say that AHIP’s plans “stand ready to work with state policymakers to remove barriers to lower insulin prices for Americans.”
 

Utah savings hopefully saving lives already

In Utah, legislators tuned out the blame game, and instead were keen to listen to patients, who had many stories about how the high cost of insulin had hurt them, said Ms. Hooley.

She noted an estimated 50,000 Utahans rely on insulin to stay alive.

Ms. Hooley and her chapter convinced legislators to pass a bill that gives insurers the option to cap patient copays at $30 per month, or to put insulin on its lowest formulary tier and waive any patient deductible. That aspect of the law does not go into effect until January 2021, but insurers are already starting to move insulin to the lowest formulary tier.

That has helped some people immediately. One state resident said her most recent insulin prescription cost $7 – instead of the usual $200.

The uninsured are not left totally high and dry either. Starting June 1, anyone in the state could buy through a state bulk-purchasing program, which guaranteed a 60% discount.

Ms. Hooley said she’d recently heard about a patient who usually spent $300 per prescription but was able to buy insulin for $100 through the program.

“Although $100 is still too much, it is nice knowing the Utah Insulin Savings Program is saving lives,” Ms. Hooley concluded.

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

Twelve U.S. states have now passed laws aimed at making insulin more affordable – and more than 30 are considering such legislation – but they all have gaps that still put the cost of this basic and essential medication out of reach for many with diabetes.

The laws only apply to health insurance through state-regulated plans, and not to the majority of health plans that cover most Americans: Medicare, Medicaid, the Veterans Affairs health system, or self-funded employer-sponsored plans.

Overall, Hannah Crabtree, an activist who writes the blog Data for Insulin, estimates state laws that limit copays, deductibles, or other out-of-pocket costs for insulin cover an average of 27% of people with diabetes across the United States.

And while diabetes activists have applauded state actions, most want more help for the under- and uninsured.

“Our chapter will be fighting harder next legislative session for the uninsured,” said Mindie Hooley, the leader of the Utah #insulin4all chapter, which successfully lobbied legislators to pass a bill signed by the state’s governor on March 30.

“With so many losing their jobs because of the pandemic, there’s no better time than now to fight for these patients who don’t have insurance,” Ms. Hooley said in an interview.

The American Diabetes Association has also been lobbying for state caps as one of many avenues for making insulin more affordable, said Stephen Habbe, the ADA’s director for state government affairs.

One in four insulin users report rationing the medication, Mr. Habbe said.

The state laws “can really provide important relief in terms of affordability for their insulin costs, which we know can be critical in terms of preserving their life and helping to prevent complications that can potentially be disabling or even deadly,” he said in an interview.

Activists with T1 International, which created the #insulin4all campaign, are working nationwide to convince state legislators to back measures that limit out-of-pocket costs for insulin, or for other diabetes medications and supplies.

Colorado, Connecticut, Delaware, Illinois, Maine, New Hampshire, New Mexico, New York, Utah, Virginia, Washington, and West Virginia have enacted such limits, with caps ranging from $25 to $100.
 

Insulin makers unfazed, blame insurers, PBMs for high prices

The three insulin manufacturers in the United States – Eli Lilly, Novo Nordisk, and Sanofi– have not overtly fought against the laws, although in July, the Pharmaceutical Research and Manufacturers of America did sue to block a related Minnesota law that provides a free emergency supply of insulin.

And the nonprofit news organization FairWarning reported in August that a lobbyist from Eli Lilly had attempted to push a Tennessee legislator to keep the uninsured from being eligible for any out-of-pocket limits.

The insulin makers have also not lowered prices in response to the mounting number of state laws.

They see no need, said Tara O’Neill Hayes, director of human welfare policy at the American Action Forum, a center right–leaning Washington, D.C., think tank.

“You’re going to do what you can get away with,” Ms. O’Neill Hayes said in an interview. “To the extent that they can keep their prices high and people are still buying, they have limited incentives to lower those costs.”

The insulin market is dysfunctional, she added. “The increasing cost of insulin seems primarily to be the result of a lack of competition in the market and convoluted drug pricing and insurance practices,” Ms. O’Neill Hayes and colleagues wrote in a report in April on federal and state attempts to address insulin affordability.

Novo Nordisk, however, maintains that drugmakers are not solely to blame.

“Everyone in the health care system has a role to play in affordability,” said Ken Inchausti, Novo Nordisk’s senior director for corporate communications. State legislation “attempts to address a systemic issue in [U.S.] health care: How benefit design can make medicines unaffordable for many, especially for those in high-deductible health plans,” he said in an interview.

“Efforts to place copay caps on insurance plans covering insulin can certainly help lower out-of-pocket costs,” said Mr. Inchausti.

Sanofi spokesperson Jon Florio said the company supports actions that increase affordable access to insulin. However, “while we support capped copays, we feel this should not be limited to just one class of medicines,” he said. Mr. Florio also noted that Sanofi provides out-of-pocket caps to anyone with commercial insurance and that anyone without insurance can buy one or multiple Sanofi insulins for a fixed price of $99 per month, up to 10 boxes of pens and/or 10-mL vials.

And Sanofi will take part in the Centers for Medicare & Medicaid Services’ new insulin demonstration program. Starting in 2021, CMS will cap insulin copays at $35 for people in Part D plans that participate.

Eli Lilly spokesperson Brad Jacklin said the company “believes in the common goal of ensuring affordable access to insulin and other life-saving medicines because nobody should have to forgo or ration because of cost.”

Lilly supports efforts “that more directly affect patients’ cost-sharing based on their health care coverage,” he said. Insurers and pharmacy benefit managers (PBMs) should pass savings on to patients, Mr. Jacklin urged. Lilly caps some insulins at $35 for the uninsured or commercially insured. The company will also participate in the CMS program.

Meanwhile, a PhRMA-sponsored website www.letstalkaboutcost.org said that, because they do not share savings, insurers and PBMs are responsible for high insulin costs.

Manufacturer assistance programs for patients with diabetes and other chronic diseases, on the other hand, can save individuals $300-$500 a year, PhRMA said in August.
 

PBMs point back at insulin manufacturers

PBMs, however, point back at drug companies. “PBMs have been able to moderate insulin costs for most consumers with insurance,” said J.C. Scott, president and CEO of the Pharmaceutical Care Management Association, the PBM trade group, in a statement.

The rising cost of insulin is caused by a lack of competition and overuse of patent extensions, PCMA maintains.

Health insurers, which, in tandem with PBMs, give insulins formulary preference based on a discounted price, are most likely to feel the impact of laws limiting out-of-pocket costs.

If they have to make up the shortfall from a patient’s reduced payment for a prescription, they will likely raise premiums, said Ms. O’Neill Hayes.

And if patients pay the same price for insulin – regardless of who makes it – drugmakers won’t have much incentive to offer discounts or rebates for formulary placement, she said. Again, that would likely lead to higher premiums.

David Allen, a spokesperson for America’s Health Insurance Plans, said in an interview that AHIP believes lack of competition has driven up insulin prices.

“High prices for insulin correspond with high health insurance costs for insulin,” he said. When CMS starts requiring drugmakers to discount their insulins for Medicare that will allow “health plans to use those savings to reduce out-of-pocket [costs] for seniors.”

He did not respond to a question as to why health insurers were not already passing savings on to commercially insured patients, especially in states with out-of-pocket limits.

Mr. Allen did say that AHIP’s plans “stand ready to work with state policymakers to remove barriers to lower insulin prices for Americans.”
 

Utah savings hopefully saving lives already

In Utah, legislators tuned out the blame game, and instead were keen to listen to patients, who had many stories about how the high cost of insulin had hurt them, said Ms. Hooley.

She noted an estimated 50,000 Utahans rely on insulin to stay alive.

Ms. Hooley and her chapter convinced legislators to pass a bill that gives insurers the option to cap patient copays at $30 per month, or to put insulin on its lowest formulary tier and waive any patient deductible. That aspect of the law does not go into effect until January 2021, but insurers are already starting to move insulin to the lowest formulary tier.

That has helped some people immediately. One state resident said her most recent insulin prescription cost $7 – instead of the usual $200.

The uninsured are not left totally high and dry either. Starting June 1, anyone in the state could buy through a state bulk-purchasing program, which guaranteed a 60% discount.

Ms. Hooley said she’d recently heard about a patient who usually spent $300 per prescription but was able to buy insulin for $100 through the program.

“Although $100 is still too much, it is nice knowing the Utah Insulin Savings Program is saving lives,” Ms. Hooley concluded.

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

Twelve U.S. states have now passed laws aimed at making insulin more affordable – and more than 30 are considering such legislation – but they all have gaps that still put the cost of this basic and essential medication out of reach for many with diabetes.

The laws only apply to health insurance through state-regulated plans, and not to the majority of health plans that cover most Americans: Medicare, Medicaid, the Veterans Affairs health system, or self-funded employer-sponsored plans.

Overall, Hannah Crabtree, an activist who writes the blog Data for Insulin, estimates state laws that limit copays, deductibles, or other out-of-pocket costs for insulin cover an average of 27% of people with diabetes across the United States.

And while diabetes activists have applauded state actions, most want more help for the under- and uninsured.

“Our chapter will be fighting harder next legislative session for the uninsured,” said Mindie Hooley, the leader of the Utah #insulin4all chapter, which successfully lobbied legislators to pass a bill signed by the state’s governor on March 30.

“With so many losing their jobs because of the pandemic, there’s no better time than now to fight for these patients who don’t have insurance,” Ms. Hooley said in an interview.

The American Diabetes Association has also been lobbying for state caps as one of many avenues for making insulin more affordable, said Stephen Habbe, the ADA’s director for state government affairs.

One in four insulin users report rationing the medication, Mr. Habbe said.

The state laws “can really provide important relief in terms of affordability for their insulin costs, which we know can be critical in terms of preserving their life and helping to prevent complications that can potentially be disabling or even deadly,” he said in an interview.

Activists with T1 International, which created the #insulin4all campaign, are working nationwide to convince state legislators to back measures that limit out-of-pocket costs for insulin, or for other diabetes medications and supplies.

Colorado, Connecticut, Delaware, Illinois, Maine, New Hampshire, New Mexico, New York, Utah, Virginia, Washington, and West Virginia have enacted such limits, with caps ranging from $25 to $100.
 

Insulin makers unfazed, blame insurers, PBMs for high prices

The three insulin manufacturers in the United States – Eli Lilly, Novo Nordisk, and Sanofi– have not overtly fought against the laws, although in July, the Pharmaceutical Research and Manufacturers of America did sue to block a related Minnesota law that provides a free emergency supply of insulin.

And the nonprofit news organization FairWarning reported in August that a lobbyist from Eli Lilly had attempted to push a Tennessee legislator to keep the uninsured from being eligible for any out-of-pocket limits.

The insulin makers have also not lowered prices in response to the mounting number of state laws.

They see no need, said Tara O’Neill Hayes, director of human welfare policy at the American Action Forum, a center right–leaning Washington, D.C., think tank.

“You’re going to do what you can get away with,” Ms. O’Neill Hayes said in an interview. “To the extent that they can keep their prices high and people are still buying, they have limited incentives to lower those costs.”

The insulin market is dysfunctional, she added. “The increasing cost of insulin seems primarily to be the result of a lack of competition in the market and convoluted drug pricing and insurance practices,” Ms. O’Neill Hayes and colleagues wrote in a report in April on federal and state attempts to address insulin affordability.

Novo Nordisk, however, maintains that drugmakers are not solely to blame.

“Everyone in the health care system has a role to play in affordability,” said Ken Inchausti, Novo Nordisk’s senior director for corporate communications. State legislation “attempts to address a systemic issue in [U.S.] health care: How benefit design can make medicines unaffordable for many, especially for those in high-deductible health plans,” he said in an interview.

“Efforts to place copay caps on insurance plans covering insulin can certainly help lower out-of-pocket costs,” said Mr. Inchausti.

Sanofi spokesperson Jon Florio said the company supports actions that increase affordable access to insulin. However, “while we support capped copays, we feel this should not be limited to just one class of medicines,” he said. Mr. Florio also noted that Sanofi provides out-of-pocket caps to anyone with commercial insurance and that anyone without insurance can buy one or multiple Sanofi insulins for a fixed price of $99 per month, up to 10 boxes of pens and/or 10-mL vials.

And Sanofi will take part in the Centers for Medicare & Medicaid Services’ new insulin demonstration program. Starting in 2021, CMS will cap insulin copays at $35 for people in Part D plans that participate.

Eli Lilly spokesperson Brad Jacklin said the company “believes in the common goal of ensuring affordable access to insulin and other life-saving medicines because nobody should have to forgo or ration because of cost.”

Lilly supports efforts “that more directly affect patients’ cost-sharing based on their health care coverage,” he said. Insurers and pharmacy benefit managers (PBMs) should pass savings on to patients, Mr. Jacklin urged. Lilly caps some insulins at $35 for the uninsured or commercially insured. The company will also participate in the CMS program.

Meanwhile, a PhRMA-sponsored website www.letstalkaboutcost.org said that, because they do not share savings, insurers and PBMs are responsible for high insulin costs.

Manufacturer assistance programs for patients with diabetes and other chronic diseases, on the other hand, can save individuals $300-$500 a year, PhRMA said in August.
 

PBMs point back at insulin manufacturers

PBMs, however, point back at drug companies. “PBMs have been able to moderate insulin costs for most consumers with insurance,” said J.C. Scott, president and CEO of the Pharmaceutical Care Management Association, the PBM trade group, in a statement.

The rising cost of insulin is caused by a lack of competition and overuse of patent extensions, PCMA maintains.

Health insurers, which, in tandem with PBMs, give insulins formulary preference based on a discounted price, are most likely to feel the impact of laws limiting out-of-pocket costs.

If they have to make up the shortfall from a patient’s reduced payment for a prescription, they will likely raise premiums, said Ms. O’Neill Hayes.

And if patients pay the same price for insulin – regardless of who makes it – drugmakers won’t have much incentive to offer discounts or rebates for formulary placement, she said. Again, that would likely lead to higher premiums.

David Allen, a spokesperson for America’s Health Insurance Plans, said in an interview that AHIP believes lack of competition has driven up insulin prices.

“High prices for insulin correspond with high health insurance costs for insulin,” he said. When CMS starts requiring drugmakers to discount their insulins for Medicare that will allow “health plans to use those savings to reduce out-of-pocket [costs] for seniors.”

He did not respond to a question as to why health insurers were not already passing savings on to commercially insured patients, especially in states with out-of-pocket limits.

Mr. Allen did say that AHIP’s plans “stand ready to work with state policymakers to remove barriers to lower insulin prices for Americans.”
 

Utah savings hopefully saving lives already

In Utah, legislators tuned out the blame game, and instead were keen to listen to patients, who had many stories about how the high cost of insulin had hurt them, said Ms. Hooley.

She noted an estimated 50,000 Utahans rely on insulin to stay alive.

Ms. Hooley and her chapter convinced legislators to pass a bill that gives insurers the option to cap patient copays at $30 per month, or to put insulin on its lowest formulary tier and waive any patient deductible. That aspect of the law does not go into effect until January 2021, but insurers are already starting to move insulin to the lowest formulary tier.

That has helped some people immediately. One state resident said her most recent insulin prescription cost $7 – instead of the usual $200.

The uninsured are not left totally high and dry either. Starting June 1, anyone in the state could buy through a state bulk-purchasing program, which guaranteed a 60% discount.

Ms. Hooley said she’d recently heard about a patient who usually spent $300 per prescription but was able to buy insulin for $100 through the program.

“Although $100 is still too much, it is nice knowing the Utah Insulin Savings Program is saving lives,” Ms. Hooley concluded.

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

For patients with suspected small-bowel bleeding, a three-variable scoring system predicted the diagnostic outcomes of video capsule endoscopy, according to the findings of a multicenter study.

“Admission to the hospital with overt bleeding and having a hemoglobin [level] of less than 6.4 g/dL were two positive predictors of a diagnosis. Being younger than 54 years old at the time of the video capsule endoscopy exam was a significant negative predictor of a diagnosis,” Neil B. Marya, MD, of the University of California, Los Angeles, and associates wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

To develop the scoring system, they analyzed retrospective data from 162 adults with suspected small-bowel bleeding who received video capsule endoscopies at the University of Massachusetts or the University of California, Los Angeles, in 2016 or 2017. Most of these individuals were outpatients with occult gastrointestinal bleeding, but nearly one-third were inpatients with overt bleeding.

In all, 70 (43%) patients had a relevant finding on video capsule endoscopy, most frequently arteriovenous malformation (26%), blood (10.5%), or ulceration (10.5%). On multivariable analysis, the odds of positive video capsule endoscopy were significantly higher when patients had been admitted to the hospital with overt bleeding (adjusted odds ratio, 2.38; 95% confidence interval, 1.05-5.39) or had a baseline hemoglobin level less than or equal to 6.4 g/dL (aOR, 2.68; 95% CI, 1.11-6.48). In contrast, patients who were younger than 54 years were significantly less likely to have diagnostic lesions (aOR, 0.25; 95% CI, 0.11-0.58). After designating these variables as A, B, and C, respectively, the researchers derived the following equation to produce the score: (0.87 x A) + (0.99 x B) – (1.38 x C). Each variable was scored as 1 (present) or 0 (absent). Based on this equation, the highest score possible score was 1.86, and the lowest possible score was –1.38.

The researchers validated this scoring system by analyzing data from 152 adults with suspected small-bowel bleeding who were examined prospectively at the two centers. The development and validation cohorts resembled each other except that the validation cohort had lower mean hemoglobin levels (8.2 g/dL versus 9.0 g/dL in the development cohort; P < .01) and higher mean blood urea nitrogen levels (25.3 mg/dL vs. 19.9 mg per dL; P =.03). Receiver operating curves were similar between the two groups (respective C-statistics, 0.70 and 0.69; P = .91).

However, the scoring system’s maximum specificity was only 30.6%, yielding a positive predictive value of only 48.6%. The associated cutoff score was greater than or equal to 0. At this cutoff, sensitivity was “at least 90%,” and negative predictive value was 83.6%. Thus, the scoring system is best suited for identifying patients who are unlikely to have a diagnostic lesion found on video capsule endoscopy, the researchers said.

“Patients with scores of less than 0 could conceivably have capsule examinations deferred,” they concluded. “For example, consider a clinician taking care of a hospitalized patient who meets criteria for undergoing video capsule endoscopy for the indication of suspected small intestinal bleeding, but finds that the patient has a suspected small-bowel bleeding capsule diagnosis score of less than 0. The clinician could decide to have their patient undergo the video capsule endoscopy as an outpatient, since the likelihood of detecting an actionable lesion is low. This decision could have a [beneficial] financial impact.”

No external funding sources were reported. Dr. Marya disclosed a recent consulting relationship with AnX Robotica. Two coinvestigators disclosed a consulting relationship with Medtronic and research support from Olympus and Medtronic.

SOURCE: Marya NB et al. Tech Innov Gastrointest Endosc. 2020 Jun 19. doi: 10.1016/j.tige.2020.06.001.

For patients with suspected small-bowel bleeding, a three-variable scoring system predicted the diagnostic outcomes of video capsule endoscopy, according to the findings of a multicenter study.

“Admission to the hospital with overt bleeding and having a hemoglobin [level] of less than 6.4 g/dL were two positive predictors of a diagnosis. Being younger than 54 years old at the time of the video capsule endoscopy exam was a significant negative predictor of a diagnosis,” Neil B. Marya, MD, of the University of California, Los Angeles, and associates wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

To develop the scoring system, they analyzed retrospective data from 162 adults with suspected small-bowel bleeding who received video capsule endoscopies at the University of Massachusetts or the University of California, Los Angeles, in 2016 or 2017. Most of these individuals were outpatients with occult gastrointestinal bleeding, but nearly one-third were inpatients with overt bleeding.

In all, 70 (43%) patients had a relevant finding on video capsule endoscopy, most frequently arteriovenous malformation (26%), blood (10.5%), or ulceration (10.5%). On multivariable analysis, the odds of positive video capsule endoscopy were significantly higher when patients had been admitted to the hospital with overt bleeding (adjusted odds ratio, 2.38; 95% confidence interval, 1.05-5.39) or had a baseline hemoglobin level less than or equal to 6.4 g/dL (aOR, 2.68; 95% CI, 1.11-6.48). In contrast, patients who were younger than 54 years were significantly less likely to have diagnostic lesions (aOR, 0.25; 95% CI, 0.11-0.58). After designating these variables as A, B, and C, respectively, the researchers derived the following equation to produce the score: (0.87 x A) + (0.99 x B) – (1.38 x C). Each variable was scored as 1 (present) or 0 (absent). Based on this equation, the highest score possible score was 1.86, and the lowest possible score was –1.38.

The researchers validated this scoring system by analyzing data from 152 adults with suspected small-bowel bleeding who were examined prospectively at the two centers. The development and validation cohorts resembled each other except that the validation cohort had lower mean hemoglobin levels (8.2 g/dL versus 9.0 g/dL in the development cohort; P < .01) and higher mean blood urea nitrogen levels (25.3 mg/dL vs. 19.9 mg per dL; P =.03). Receiver operating curves were similar between the two groups (respective C-statistics, 0.70 and 0.69; P = .91).

However, the scoring system’s maximum specificity was only 30.6%, yielding a positive predictive value of only 48.6%. The associated cutoff score was greater than or equal to 0. At this cutoff, sensitivity was “at least 90%,” and negative predictive value was 83.6%. Thus, the scoring system is best suited for identifying patients who are unlikely to have a diagnostic lesion found on video capsule endoscopy, the researchers said.

“Patients with scores of less than 0 could conceivably have capsule examinations deferred,” they concluded. “For example, consider a clinician taking care of a hospitalized patient who meets criteria for undergoing video capsule endoscopy for the indication of suspected small intestinal bleeding, but finds that the patient has a suspected small-bowel bleeding capsule diagnosis score of less than 0. The clinician could decide to have their patient undergo the video capsule endoscopy as an outpatient, since the likelihood of detecting an actionable lesion is low. This decision could have a [beneficial] financial impact.”

No external funding sources were reported. Dr. Marya disclosed a recent consulting relationship with AnX Robotica. Two coinvestigators disclosed a consulting relationship with Medtronic and research support from Olympus and Medtronic.

SOURCE: Marya NB et al. Tech Innov Gastrointest Endosc. 2020 Jun 19. doi: 10.1016/j.tige.2020.06.001.

For patients with suspected small-bowel bleeding, a three-variable scoring system predicted the diagnostic outcomes of video capsule endoscopy, according to the findings of a multicenter study.

“Admission to the hospital with overt bleeding and having a hemoglobin [level] of less than 6.4 g/dL were two positive predictors of a diagnosis. Being younger than 54 years old at the time of the video capsule endoscopy exam was a significant negative predictor of a diagnosis,” Neil B. Marya, MD, of the University of California, Los Angeles, and associates wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

To develop the scoring system, they analyzed retrospective data from 162 adults with suspected small-bowel bleeding who received video capsule endoscopies at the University of Massachusetts or the University of California, Los Angeles, in 2016 or 2017. Most of these individuals were outpatients with occult gastrointestinal bleeding, but nearly one-third were inpatients with overt bleeding.

In all, 70 (43%) patients had a relevant finding on video capsule endoscopy, most frequently arteriovenous malformation (26%), blood (10.5%), or ulceration (10.5%). On multivariable analysis, the odds of positive video capsule endoscopy were significantly higher when patients had been admitted to the hospital with overt bleeding (adjusted odds ratio, 2.38; 95% confidence interval, 1.05-5.39) or had a baseline hemoglobin level less than or equal to 6.4 g/dL (aOR, 2.68; 95% CI, 1.11-6.48). In contrast, patients who were younger than 54 years were significantly less likely to have diagnostic lesions (aOR, 0.25; 95% CI, 0.11-0.58). After designating these variables as A, B, and C, respectively, the researchers derived the following equation to produce the score: (0.87 x A) + (0.99 x B) – (1.38 x C). Each variable was scored as 1 (present) or 0 (absent). Based on this equation, the highest score possible score was 1.86, and the lowest possible score was –1.38.

The researchers validated this scoring system by analyzing data from 152 adults with suspected small-bowel bleeding who were examined prospectively at the two centers. The development and validation cohorts resembled each other except that the validation cohort had lower mean hemoglobin levels (8.2 g/dL versus 9.0 g/dL in the development cohort; P < .01) and higher mean blood urea nitrogen levels (25.3 mg/dL vs. 19.9 mg per dL; P =.03). Receiver operating curves were similar between the two groups (respective C-statistics, 0.70 and 0.69; P = .91).

However, the scoring system’s maximum specificity was only 30.6%, yielding a positive predictive value of only 48.6%. The associated cutoff score was greater than or equal to 0. At this cutoff, sensitivity was “at least 90%,” and negative predictive value was 83.6%. Thus, the scoring system is best suited for identifying patients who are unlikely to have a diagnostic lesion found on video capsule endoscopy, the researchers said.

“Patients with scores of less than 0 could conceivably have capsule examinations deferred,” they concluded. “For example, consider a clinician taking care of a hospitalized patient who meets criteria for undergoing video capsule endoscopy for the indication of suspected small intestinal bleeding, but finds that the patient has a suspected small-bowel bleeding capsule diagnosis score of less than 0. The clinician could decide to have their patient undergo the video capsule endoscopy as an outpatient, since the likelihood of detecting an actionable lesion is low. This decision could have a [beneficial] financial impact.”

No external funding sources were reported. Dr. Marya disclosed a recent consulting relationship with AnX Robotica. Two coinvestigators disclosed a consulting relationship with Medtronic and research support from Olympus and Medtronic.

SOURCE: Marya NB et al. Tech Innov Gastrointest Endosc. 2020 Jun 19. doi: 10.1016/j.tige.2020.06.001.

Atezolizumab (Tecentriq) plus paclitaxel is ineffective in patients with previously untreated, inoperable, locally advanced or metastatic triple-negative breast cancer (TNBC), according to an alert from the Food and Drug Administration.

The FDA said the phase 3 IMpassion131 trial showed that atezolizumab plus paclitaxel did not significantly reduce the risk of cancer progression and death, when compared with paclitaxel plus placebo, in programmed death-ligand 1 (PD-L1)–positive patients.

“Additionally, interim overall survival results favored paclitaxel plus placebo over paclitaxel plus atezolizumab in both the PD-L1-positive population and total population,” the FDA noted.

As a result, “health care professionals should not replace paclitaxel protein-bound (Abraxane) with paclitaxel in clinical practice,” the FDA advised.

Atezolizumab is approved for use in combination with protein-bound paclitaxel, also known as nanoparticle albumin–bound paclitaxel (nab-paclitaxel), to treat patients with unresectable, locally advanced, or metastatic TNBC whose tumors express PD-L1, as detected by an FDA-approved test. The combination was granted accelerated approval for this indication last year.

Atezolizumab plus nab-paclitaxel is the combination most often used in PD-L1-positive TNBC, as opposed to atezolizumab and unbound paclitaxel, said Melinda L. Telli, MD, an associate professor of medicine and director of the Stanford Cancer Institute Breast Cancer Program at Stanford (Calif.) University.

However, as the FDA noted, “continued approval of atezolizumab in combination with [nab-paclitaxel] may be contingent on proven benefit of the treatment in additional trials.”

Dr. Telli explained that atezolizumab was granted accelerated approval for the treatment of PD-L1-positive TNBC based on results of the phase 3 IMpassion130 trial, which compared nab-paclitaxel plus atezolizumab with nab-paclitaxel plus placebo.

“Additional data from IMpassion131 was hoped to be used to support the conversion of the accelerated approval to a full approval. Since IMpassion131 was negative, it unfortunately places the status of atezolizumab in [TNBC] in jeopardy as the benefits were not corroborated. The FDA may move to revoke the approval of atezolizumab for [TNBC],” Dr. Telli said.

In its alert, the FDA stated that it “will review the findings of IMpassion131 and will communicate new information regarding the IMpassion131 results and any potential changes to prescribing information.”

“We need to wait for full presentation and publication of the study results, but, in my assessment, the negative results in IMpassion131 are most likely due to differences in patient selection [from IMpassion130],” Dr. Telli said.

Results from IMpassion131 are scheduled to be presented at the ESMO Virtual Congress 2020.

The IMpassion trials were funded by Roche, maker of atezolizumab. Dr. Telli disclosed relationships with AbbVie, AstraZeneca, Merck, PharmaMar, Pfizer, and Tesaro.
 

[email protected]

Atezolizumab (Tecentriq) plus paclitaxel is ineffective in patients with previously untreated, inoperable, locally advanced or metastatic triple-negative breast cancer (TNBC), according to an alert from the Food and Drug Administration.

The FDA said the phase 3 IMpassion131 trial showed that atezolizumab plus paclitaxel did not significantly reduce the risk of cancer progression and death, when compared with paclitaxel plus placebo, in programmed death-ligand 1 (PD-L1)–positive patients.

“Additionally, interim overall survival results favored paclitaxel plus placebo over paclitaxel plus atezolizumab in both the PD-L1-positive population and total population,” the FDA noted.

As a result, “health care professionals should not replace paclitaxel protein-bound (Abraxane) with paclitaxel in clinical practice,” the FDA advised.

Atezolizumab is approved for use in combination with protein-bound paclitaxel, also known as nanoparticle albumin–bound paclitaxel (nab-paclitaxel), to treat patients with unresectable, locally advanced, or metastatic TNBC whose tumors express PD-L1, as detected by an FDA-approved test. The combination was granted accelerated approval for this indication last year.

Atezolizumab plus nab-paclitaxel is the combination most often used in PD-L1-positive TNBC, as opposed to atezolizumab and unbound paclitaxel, said Melinda L. Telli, MD, an associate professor of medicine and director of the Stanford Cancer Institute Breast Cancer Program at Stanford (Calif.) University.

However, as the FDA noted, “continued approval of atezolizumab in combination with [nab-paclitaxel] may be contingent on proven benefit of the treatment in additional trials.”

Dr. Telli explained that atezolizumab was granted accelerated approval for the treatment of PD-L1-positive TNBC based on results of the phase 3 IMpassion130 trial, which compared nab-paclitaxel plus atezolizumab with nab-paclitaxel plus placebo.

“Additional data from IMpassion131 was hoped to be used to support the conversion of the accelerated approval to a full approval. Since IMpassion131 was negative, it unfortunately places the status of atezolizumab in [TNBC] in jeopardy as the benefits were not corroborated. The FDA may move to revoke the approval of atezolizumab for [TNBC],” Dr. Telli said.

In its alert, the FDA stated that it “will review the findings of IMpassion131 and will communicate new information regarding the IMpassion131 results and any potential changes to prescribing information.”

“We need to wait for full presentation and publication of the study results, but, in my assessment, the negative results in IMpassion131 are most likely due to differences in patient selection [from IMpassion130],” Dr. Telli said.

Results from IMpassion131 are scheduled to be presented at the ESMO Virtual Congress 2020.

The IMpassion trials were funded by Roche, maker of atezolizumab. Dr. Telli disclosed relationships with AbbVie, AstraZeneca, Merck, PharmaMar, Pfizer, and Tesaro.
 

[email protected]

Atezolizumab (Tecentriq) plus paclitaxel is ineffective in patients with previously untreated, inoperable, locally advanced or metastatic triple-negative breast cancer (TNBC), according to an alert from the Food and Drug Administration.

The FDA said the phase 3 IMpassion131 trial showed that atezolizumab plus paclitaxel did not significantly reduce the risk of cancer progression and death, when compared with paclitaxel plus placebo, in programmed death-ligand 1 (PD-L1)–positive patients.

“Additionally, interim overall survival results favored paclitaxel plus placebo over paclitaxel plus atezolizumab in both the PD-L1-positive population and total population,” the FDA noted.

As a result, “health care professionals should not replace paclitaxel protein-bound (Abraxane) with paclitaxel in clinical practice,” the FDA advised.

Atezolizumab is approved for use in combination with protein-bound paclitaxel, also known as nanoparticle albumin–bound paclitaxel (nab-paclitaxel), to treat patients with unresectable, locally advanced, or metastatic TNBC whose tumors express PD-L1, as detected by an FDA-approved test. The combination was granted accelerated approval for this indication last year.

Atezolizumab plus nab-paclitaxel is the combination most often used in PD-L1-positive TNBC, as opposed to atezolizumab and unbound paclitaxel, said Melinda L. Telli, MD, an associate professor of medicine and director of the Stanford Cancer Institute Breast Cancer Program at Stanford (Calif.) University.

However, as the FDA noted, “continued approval of atezolizumab in combination with [nab-paclitaxel] may be contingent on proven benefit of the treatment in additional trials.”

Dr. Telli explained that atezolizumab was granted accelerated approval for the treatment of PD-L1-positive TNBC based on results of the phase 3 IMpassion130 trial, which compared nab-paclitaxel plus atezolizumab with nab-paclitaxel plus placebo.

“Additional data from IMpassion131 was hoped to be used to support the conversion of the accelerated approval to a full approval. Since IMpassion131 was negative, it unfortunately places the status of atezolizumab in [TNBC] in jeopardy as the benefits were not corroborated. The FDA may move to revoke the approval of atezolizumab for [TNBC],” Dr. Telli said.

In its alert, the FDA stated that it “will review the findings of IMpassion131 and will communicate new information regarding the IMpassion131 results and any potential changes to prescribing information.”

“We need to wait for full presentation and publication of the study results, but, in my assessment, the negative results in IMpassion131 are most likely due to differences in patient selection [from IMpassion130],” Dr. Telli said.

Results from IMpassion131 are scheduled to be presented at the ESMO Virtual Congress 2020.

The IMpassion trials were funded by Roche, maker of atezolizumab. Dr. Telli disclosed relationships with AbbVie, AstraZeneca, Merck, PharmaMar, Pfizer, and Tesaro.
 

[email protected]

A history of liver transplant conveyed no increased risk of death from COVID-19 infections, according to data from a multicenter cohort study of 151 transplant recipients who became infected.

Although current data suggest a possible increased risk of adverse outcomes if liver transplant patients develop COVID-19 infections, the effects remain unclear, wrote Gwilym J. Webb, PhD, of the University of Oxford (England) and colleagues.

In a study published in the Lancet Gastroenterology & Hepatology, the researchers identified adults from 18 countries who had laboratory-confirmed COVID-19 infections between March 25, 2020, and June 26, 2020. The average age of the patients was 60 years, and 68% were men. A contemporaneous group of 627 consecutive adults with confirmed COVID-19 infections who had not undergone liver transplants served as controls.

Overall, 28 of the liver transplant patients and 167 of the controls died (19% vs. 27%; P = .046).

In addition, no differences appeared between infected transplant patients and infected controls in terms of hospitalization (82% vs. 76%) and the need for intensive care (31% vs. 30%), although the transplant patients were significantly more likely to require invasive ventilation (20% vs. 5%).

However, in a multivariate analysis, older age, serum creatinine concentration, and the presence of nonliver cancers were independently associated with increased risk of death in the liver transplant patients, with odds ratios of 1.06 for each year increase in age, 1.57 for each mg/dL increase in serum creatinine concentration, and 18.30 with the presence of a nonliver cancer.

The study findings were limited by several factors including the potential overreporting of severe COVID-19 cases because of reporting bias in the transplant registry, as well as the inability of the sample size to rule out mortality differences, the differences in comorbidities between the transplant patients and controls, and the impact of unmeasured confounding variables such as diet, physical activity, or fibrosis or cirrhosis in recipient grafts, the researchers noted. However, the results suggest that a history of liver transplantation does not increase the risk of death following COVID-19 infection, they wrote.

“Thus, traditional risk factors for adverse outcomes from COVID-19 should be preferentially considered when considering the risks and benefits of hospital attendance, immunosuppression, and social-distancing requirements for liver transplant recipients during the ongoing COVID-19 pandemic,” they concluded.

Focus on comorbidities and combined transplants

“Given that age and presence of comorbidities were significantly associated with risk of death in the cohorts of patients who had and had not undergone liver transplantation, greater emphasis should be placed on other coexisting comorbidities, rather than transplantation status per se, when risk-stratifying liver transplant recipients,” the researchers noted. “Indirectly, these findings suggest that liver transplantation, where indicated, should not be delayed during the COVID-19 pandemic, and that supportive care should not be limited for patients with existing liver transplants with COVID-19,” they suggested.

Given the high prevalence of COVID-19 in many countries, “it is inevitable that liver transplant patients will become infected,” said Wajahat Mehal, MD, of Yale University, New Haven, Conn., in an interview.

Going forward, “it is important to know the natural history of COVID in the immunocompromised population,” he emphasized.

One of the study limitations was the lack of data on how patients’ immunosuppression regimens were changed, if at all, while they were infected. “Since some other immunocompromised patients have had a higher rate of complications [in the wake of COVID-19 infections], I was pleasantly surprised that liver transplant recipients did so well,” Dr. Mehal said.

Dr. Mehal noted that additional research is needed to promote safety in patients with liver disease in the context of COVID-19. “It would be important to evaluate combined transplants, particularly combined liver/kidney transplants,” he said.

The study was supported by the European Association for the Study of the Liver, the National Institutes of Health, and the United Kingdom National Institute for Health Research. Lead author Dr. Webb had no financial conflicts to disclose. One coauthor disclosed unrelated fees from AbbVie and grants from the Fondation du Centre Hospitalier de l’Université de Montréal. Dr. Mehal had no financial conflicts to disclose.

SOURCE: Webb GJ et al. Lancet Gastroenterol Hepatol. 2020 Aug 28. doi: 10.1016/ S2468-1253(20)30271-5.

A history of liver transplant conveyed no increased risk of death from COVID-19 infections, according to data from a multicenter cohort study of 151 transplant recipients who became infected.

Although current data suggest a possible increased risk of adverse outcomes if liver transplant patients develop COVID-19 infections, the effects remain unclear, wrote Gwilym J. Webb, PhD, of the University of Oxford (England) and colleagues.

In a study published in the Lancet Gastroenterology & Hepatology, the researchers identified adults from 18 countries who had laboratory-confirmed COVID-19 infections between March 25, 2020, and June 26, 2020. The average age of the patients was 60 years, and 68% were men. A contemporaneous group of 627 consecutive adults with confirmed COVID-19 infections who had not undergone liver transplants served as controls.

Overall, 28 of the liver transplant patients and 167 of the controls died (19% vs. 27%; P = .046).

In addition, no differences appeared between infected transplant patients and infected controls in terms of hospitalization (82% vs. 76%) and the need for intensive care (31% vs. 30%), although the transplant patients were significantly more likely to require invasive ventilation (20% vs. 5%).

However, in a multivariate analysis, older age, serum creatinine concentration, and the presence of nonliver cancers were independently associated with increased risk of death in the liver transplant patients, with odds ratios of 1.06 for each year increase in age, 1.57 for each mg/dL increase in serum creatinine concentration, and 18.30 with the presence of a nonliver cancer.

The study findings were limited by several factors including the potential overreporting of severe COVID-19 cases because of reporting bias in the transplant registry, as well as the inability of the sample size to rule out mortality differences, the differences in comorbidities between the transplant patients and controls, and the impact of unmeasured confounding variables such as diet, physical activity, or fibrosis or cirrhosis in recipient grafts, the researchers noted. However, the results suggest that a history of liver transplantation does not increase the risk of death following COVID-19 infection, they wrote.

“Thus, traditional risk factors for adverse outcomes from COVID-19 should be preferentially considered when considering the risks and benefits of hospital attendance, immunosuppression, and social-distancing requirements for liver transplant recipients during the ongoing COVID-19 pandemic,” they concluded.

Focus on comorbidities and combined transplants

“Given that age and presence of comorbidities were significantly associated with risk of death in the cohorts of patients who had and had not undergone liver transplantation, greater emphasis should be placed on other coexisting comorbidities, rather than transplantation status per se, when risk-stratifying liver transplant recipients,” the researchers noted. “Indirectly, these findings suggest that liver transplantation, where indicated, should not be delayed during the COVID-19 pandemic, and that supportive care should not be limited for patients with existing liver transplants with COVID-19,” they suggested.

Given the high prevalence of COVID-19 in many countries, “it is inevitable that liver transplant patients will become infected,” said Wajahat Mehal, MD, of Yale University, New Haven, Conn., in an interview.

Going forward, “it is important to know the natural history of COVID in the immunocompromised population,” he emphasized.

One of the study limitations was the lack of data on how patients’ immunosuppression regimens were changed, if at all, while they were infected. “Since some other immunocompromised patients have had a higher rate of complications [in the wake of COVID-19 infections], I was pleasantly surprised that liver transplant recipients did so well,” Dr. Mehal said.

Dr. Mehal noted that additional research is needed to promote safety in patients with liver disease in the context of COVID-19. “It would be important to evaluate combined transplants, particularly combined liver/kidney transplants,” he said.

The study was supported by the European Association for the Study of the Liver, the National Institutes of Health, and the United Kingdom National Institute for Health Research. Lead author Dr. Webb had no financial conflicts to disclose. One coauthor disclosed unrelated fees from AbbVie and grants from the Fondation du Centre Hospitalier de l’Université de Montréal. Dr. Mehal had no financial conflicts to disclose.

SOURCE: Webb GJ et al. Lancet Gastroenterol Hepatol. 2020 Aug 28. doi: 10.1016/ S2468-1253(20)30271-5.

A history of liver transplant conveyed no increased risk of death from COVID-19 infections, according to data from a multicenter cohort study of 151 transplant recipients who became infected.

Although current data suggest a possible increased risk of adverse outcomes if liver transplant patients develop COVID-19 infections, the effects remain unclear, wrote Gwilym J. Webb, PhD, of the University of Oxford (England) and colleagues.

In a study published in the Lancet Gastroenterology & Hepatology, the researchers identified adults from 18 countries who had laboratory-confirmed COVID-19 infections between March 25, 2020, and June 26, 2020. The average age of the patients was 60 years, and 68% were men. A contemporaneous group of 627 consecutive adults with confirmed COVID-19 infections who had not undergone liver transplants served as controls.

Overall, 28 of the liver transplant patients and 167 of the controls died (19% vs. 27%; P = .046).

In addition, no differences appeared between infected transplant patients and infected controls in terms of hospitalization (82% vs. 76%) and the need for intensive care (31% vs. 30%), although the transplant patients were significantly more likely to require invasive ventilation (20% vs. 5%).

However, in a multivariate analysis, older age, serum creatinine concentration, and the presence of nonliver cancers were independently associated with increased risk of death in the liver transplant patients, with odds ratios of 1.06 for each year increase in age, 1.57 for each mg/dL increase in serum creatinine concentration, and 18.30 with the presence of a nonliver cancer.

The study findings were limited by several factors including the potential overreporting of severe COVID-19 cases because of reporting bias in the transplant registry, as well as the inability of the sample size to rule out mortality differences, the differences in comorbidities between the transplant patients and controls, and the impact of unmeasured confounding variables such as diet, physical activity, or fibrosis or cirrhosis in recipient grafts, the researchers noted. However, the results suggest that a history of liver transplantation does not increase the risk of death following COVID-19 infection, they wrote.

“Thus, traditional risk factors for adverse outcomes from COVID-19 should be preferentially considered when considering the risks and benefits of hospital attendance, immunosuppression, and social-distancing requirements for liver transplant recipients during the ongoing COVID-19 pandemic,” they concluded.

Focus on comorbidities and combined transplants

“Given that age and presence of comorbidities were significantly associated with risk of death in the cohorts of patients who had and had not undergone liver transplantation, greater emphasis should be placed on other coexisting comorbidities, rather than transplantation status per se, when risk-stratifying liver transplant recipients,” the researchers noted. “Indirectly, these findings suggest that liver transplantation, where indicated, should not be delayed during the COVID-19 pandemic, and that supportive care should not be limited for patients with existing liver transplants with COVID-19,” they suggested.

Given the high prevalence of COVID-19 in many countries, “it is inevitable that liver transplant patients will become infected,” said Wajahat Mehal, MD, of Yale University, New Haven, Conn., in an interview.

Going forward, “it is important to know the natural history of COVID in the immunocompromised population,” he emphasized.

One of the study limitations was the lack of data on how patients’ immunosuppression regimens were changed, if at all, while they were infected. “Since some other immunocompromised patients have had a higher rate of complications [in the wake of COVID-19 infections], I was pleasantly surprised that liver transplant recipients did so well,” Dr. Mehal said.

Dr. Mehal noted that additional research is needed to promote safety in patients with liver disease in the context of COVID-19. “It would be important to evaluate combined transplants, particularly combined liver/kidney transplants,” he said.

The study was supported by the European Association for the Study of the Liver, the National Institutes of Health, and the United Kingdom National Institute for Health Research. Lead author Dr. Webb had no financial conflicts to disclose. One coauthor disclosed unrelated fees from AbbVie and grants from the Fondation du Centre Hospitalier de l’Université de Montréal. Dr. Mehal had no financial conflicts to disclose.

SOURCE: Webb GJ et al. Lancet Gastroenterol Hepatol. 2020 Aug 28. doi: 10.1016/ S2468-1253(20)30271-5.

Knowing it may be met with some skepticism, the Trump administration Thursday announced a sweeping plan that officials say will transform health care in rural America.

Even before the coronavirus pandemic reached into the nation’s less-populated regions, rural Americans were sicker, poorer, and older than the rest of the country. Hospitals are shuttering at record rates, and health care experts have long called for changes.

The new plan, released by the Department of Health & Human Services Secretary Alex M. Azar, II, acknowledges the gaps in health care and other problems facing rural America. It lists a litany of projects and directives, with many already underway or announced within federal agencies.

“We cannot just tinker around the edges of a rural healthcare system that has struggled for too long,” Azar said in a prepared statement.

Yet, that is exactly what experts say the administration continues to do.

“They tinker around the edges,” said Tommy Barnhart, former president of the National Rural Health Association. And he added, “there’s a lot of political hype” that has happened under President Trump, as well as previous presidents.

In the past few months, rural health care has increasingly become a focus for Mr. Trump, whose polling numbers are souring as COVID-19 kills hundreds of Americans every day, drives down restaurant demand for some farm products, and spreads through meatpacking plants. Rural states including Iowa and the Dakotas are reporting the latest surges in cases.

This announcement comes in response to Mr. Trump’s executive order last month calling for improved rural health and telehealth access. Earlier this week, three federal agencies also announced they would team up to address gaps in rural broadband service – a key need because large portions of the plan seek to expand telehealth.

The plan is more than 70 pages long and the word “telehealth” appears more than 90 times, with a focus on projects across HHS, including the Health Resources and Services Administration and the Centers for Medicare & Medicaid Services.

Mr. Barnhart said CMS has passed some public health emergency waivers since the beginning of the pandemic that helped rural facilities get more funding, including one that specifically was designed to provide additional money for telehealth services. However, those waivers are set to expire when the coronavirus emergency ends. Officials have not yet set a date for when the federal emergency will end.

Andrew Jay Schwartzman, senior counselor to the Benton Institute for Broadband & Society, a private foundation that works to ensure greater Internet access, said there are multiple challenges with implementing telehealth across the nation. Many initiatives for robust telehealth programs need fast bandwidth, yet getting the money and setting up the necessary infrastructure is very difficult, he said.

“It will be a long time before this kind of technology will be readily available to much of the country,” he said.

Ge Bai, associate professor of accounting and health policy at Johns Hopkins University in Baltimore, noted that telehealth was short on funding in the HHS initiative. However, she said, the focus on telehealth, as well as a proposed shift in payment for small rural hospitals and changing workforce licensing requirements, had good potential.

“We are so close to the election that this is probably more of a messaging issue to cater to rural residents,” Ms. Bai said. “But it doesn’t matter who will be president. This report will give the next administration useful guidance.”

The American Hospital Association, representing 5,000 hospitals nationwide, sent a letter to Mr. Trump last week recommending a host of steps the administration could take. As of late Thursday, AHA was still reviewing the HHS plan but said it was “encouraged by the increased attention on rural health care.”

Buried within the HHS announcement are technical initiatives, such as a contract to help clinics and hospitals integrate care, and detailed efforts to address gaps in care, including a proposal to increase funding for school-based mental health programs in the president’s 2021 budget.

A senior HHS official said that, while some actions have been taken in recent months to improve rural health — such as the $11 billion provided to rural hospitals through coronavirus relief funding — more is needed.

“We’re putting our stake in the ground that the time for talk is over,” he said. “We’re going to move forward.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Knowing it may be met with some skepticism, the Trump administration Thursday announced a sweeping plan that officials say will transform health care in rural America.

Even before the coronavirus pandemic reached into the nation’s less-populated regions, rural Americans were sicker, poorer, and older than the rest of the country. Hospitals are shuttering at record rates, and health care experts have long called for changes.

The new plan, released by the Department of Health & Human Services Secretary Alex M. Azar, II, acknowledges the gaps in health care and other problems facing rural America. It lists a litany of projects and directives, with many already underway or announced within federal agencies.

“We cannot just tinker around the edges of a rural healthcare system that has struggled for too long,” Azar said in a prepared statement.

Yet, that is exactly what experts say the administration continues to do.

“They tinker around the edges,” said Tommy Barnhart, former president of the National Rural Health Association. And he added, “there’s a lot of political hype” that has happened under President Trump, as well as previous presidents.

In the past few months, rural health care has increasingly become a focus for Mr. Trump, whose polling numbers are souring as COVID-19 kills hundreds of Americans every day, drives down restaurant demand for some farm products, and spreads through meatpacking plants. Rural states including Iowa and the Dakotas are reporting the latest surges in cases.

This announcement comes in response to Mr. Trump’s executive order last month calling for improved rural health and telehealth access. Earlier this week, three federal agencies also announced they would team up to address gaps in rural broadband service – a key need because large portions of the plan seek to expand telehealth.

The plan is more than 70 pages long and the word “telehealth” appears more than 90 times, with a focus on projects across HHS, including the Health Resources and Services Administration and the Centers for Medicare & Medicaid Services.

Mr. Barnhart said CMS has passed some public health emergency waivers since the beginning of the pandemic that helped rural facilities get more funding, including one that specifically was designed to provide additional money for telehealth services. However, those waivers are set to expire when the coronavirus emergency ends. Officials have not yet set a date for when the federal emergency will end.

Andrew Jay Schwartzman, senior counselor to the Benton Institute for Broadband & Society, a private foundation that works to ensure greater Internet access, said there are multiple challenges with implementing telehealth across the nation. Many initiatives for robust telehealth programs need fast bandwidth, yet getting the money and setting up the necessary infrastructure is very difficult, he said.

“It will be a long time before this kind of technology will be readily available to much of the country,” he said.

Ge Bai, associate professor of accounting and health policy at Johns Hopkins University in Baltimore, noted that telehealth was short on funding in the HHS initiative. However, she said, the focus on telehealth, as well as a proposed shift in payment for small rural hospitals and changing workforce licensing requirements, had good potential.

“We are so close to the election that this is probably more of a messaging issue to cater to rural residents,” Ms. Bai said. “But it doesn’t matter who will be president. This report will give the next administration useful guidance.”

The American Hospital Association, representing 5,000 hospitals nationwide, sent a letter to Mr. Trump last week recommending a host of steps the administration could take. As of late Thursday, AHA was still reviewing the HHS plan but said it was “encouraged by the increased attention on rural health care.”

Buried within the HHS announcement are technical initiatives, such as a contract to help clinics and hospitals integrate care, and detailed efforts to address gaps in care, including a proposal to increase funding for school-based mental health programs in the president’s 2021 budget.

A senior HHS official said that, while some actions have been taken in recent months to improve rural health — such as the $11 billion provided to rural hospitals through coronavirus relief funding — more is needed.

“We’re putting our stake in the ground that the time for talk is over,” he said. “We’re going to move forward.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Knowing it may be met with some skepticism, the Trump administration Thursday announced a sweeping plan that officials say will transform health care in rural America.

Even before the coronavirus pandemic reached into the nation’s less-populated regions, rural Americans were sicker, poorer, and older than the rest of the country. Hospitals are shuttering at record rates, and health care experts have long called for changes.

The new plan, released by the Department of Health & Human Services Secretary Alex M. Azar, II, acknowledges the gaps in health care and other problems facing rural America. It lists a litany of projects and directives, with many already underway or announced within federal agencies.

“We cannot just tinker around the edges of a rural healthcare system that has struggled for too long,” Azar said in a prepared statement.

Yet, that is exactly what experts say the administration continues to do.

“They tinker around the edges,” said Tommy Barnhart, former president of the National Rural Health Association. And he added, “there’s a lot of political hype” that has happened under President Trump, as well as previous presidents.

In the past few months, rural health care has increasingly become a focus for Mr. Trump, whose polling numbers are souring as COVID-19 kills hundreds of Americans every day, drives down restaurant demand for some farm products, and spreads through meatpacking plants. Rural states including Iowa and the Dakotas are reporting the latest surges in cases.

This announcement comes in response to Mr. Trump’s executive order last month calling for improved rural health and telehealth access. Earlier this week, three federal agencies also announced they would team up to address gaps in rural broadband service – a key need because large portions of the plan seek to expand telehealth.

The plan is more than 70 pages long and the word “telehealth” appears more than 90 times, with a focus on projects across HHS, including the Health Resources and Services Administration and the Centers for Medicare & Medicaid Services.

Mr. Barnhart said CMS has passed some public health emergency waivers since the beginning of the pandemic that helped rural facilities get more funding, including one that specifically was designed to provide additional money for telehealth services. However, those waivers are set to expire when the coronavirus emergency ends. Officials have not yet set a date for when the federal emergency will end.

Andrew Jay Schwartzman, senior counselor to the Benton Institute for Broadband & Society, a private foundation that works to ensure greater Internet access, said there are multiple challenges with implementing telehealth across the nation. Many initiatives for robust telehealth programs need fast bandwidth, yet getting the money and setting up the necessary infrastructure is very difficult, he said.

“It will be a long time before this kind of technology will be readily available to much of the country,” he said.

Ge Bai, associate professor of accounting and health policy at Johns Hopkins University in Baltimore, noted that telehealth was short on funding in the HHS initiative. However, she said, the focus on telehealth, as well as a proposed shift in payment for small rural hospitals and changing workforce licensing requirements, had good potential.

“We are so close to the election that this is probably more of a messaging issue to cater to rural residents,” Ms. Bai said. “But it doesn’t matter who will be president. This report will give the next administration useful guidance.”

The American Hospital Association, representing 5,000 hospitals nationwide, sent a letter to Mr. Trump last week recommending a host of steps the administration could take. As of late Thursday, AHA was still reviewing the HHS plan but said it was “encouraged by the increased attention on rural health care.”

Buried within the HHS announcement are technical initiatives, such as a contract to help clinics and hospitals integrate care, and detailed efforts to address gaps in care, including a proposal to increase funding for school-based mental health programs in the president’s 2021 budget.

A senior HHS official said that, while some actions have been taken in recent months to improve rural health — such as the $11 billion provided to rural hospitals through coronavirus relief funding — more is needed.

“We’re putting our stake in the ground that the time for talk is over,” he said. “We’re going to move forward.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

In the very near future, clinicians injecting dermal fillers on the face will have the benefit of a guided “smart” needle that senses blood vessels, thereby dramatically reducing the risk of adverse events such as necrosis and blindness.

That is the goal of an experienced team composed of leading clinicians, academics, and researchers developing S³ Inject, a first-in-class safety innovation that has entered human trials.

“When physicians inject the fillers, they hope experience and technique will enable them to avoid adverse events,” Irina Erenburg, PhD, said during the virtual annual Masters of Aesthetics Symposium. “If they inadvertently hit a blood vessel, the filler can actually occlude that vessel and cause either an infarct of the skin or, in certain serious cases, blindness. This is a challenging adverse event that every injector is focused on avoiding. While hyaluronidase is used as a rescue [medication] in certain cases, the risk is real,” she added.

Vision abnormalities, including blindness, and necrosis are among the adverse events associated with dermal fillers that have been reported to the Food and Drug Administration.

S³ Inject is a sensing needle that can differentiate tissues such as fat, blood vessels, and muscle. Its proprietary algorithms provide immediate feedback via a micro LED light embedded in the needle hub. Results from recent human trials demonstrate that, as the needle tip passes through different biological tissues and fluids, “it senses changes in specific electrical properties and with that information sends a very precise signal to the needle hub,” said Dr. Erenburg, CEO and President of Waltham, Mass.–based Blossom Innovations, a company focused on developing early stage medical devices in dermatology. “With that information, the physician can make real-time treatment decisions.”

Currently, in order to determine if the needle is in a blood vessel, physicians pull back on the syringe and look for a flash of blood. “In speaking with physicians, the pull back technique has limitations, in part, because filler in the syringe can limit easy pull back to check the presence of a blood vessel,” she said. “Our needles provide an immediate response for a safer injection.”

Blossom Innovations has developed a proprietary manufacturing process that will initially target 27 gauge needles, but over time it plans to introduce multiple sizes, as well as cannulas.

“The physicians in our industry are committed to patient safety and they’re looking for better outcomes with a solution that does not impact their technique,” said Dr. Erenburg, who founded Blossom Innovations along with R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston; Dieter Manstein, MD, PhD, also at Massachusetts General Hospital; and Henry H.L. Chan, MD, PhD, of the Hong Kong Dermatology and Laser Center. During market research for S³ Inject, which was conducted with 15 leading injectors, thought leaders, and trend makers, the country’s leading injectors expressed strong interest in “solutions that allow them to provide additional safety for their patients and provide personal reassurance to the physician,” she said. “They definitely would want to train all their physicians and injectors on its use.”

As clinical testing continues, the company is preparing to submit data to the FDA’s Premarket Notification program, known as the 510(k) process. “Our intent is to create a scale-up manufacturing over the course of the coming year in time for our clearance, with a planned launch at the end of 2021,” Dr. Erenburg said. “Based on our clinical research and physician discussions, we are confident that S³ Inject is a breakthrough safety technology which will drive a better outcome for patients.”

Dr. Erenburg is an employee of Blossom Innovations.

[email protected]

In the very near future, clinicians injecting dermal fillers on the face will have the benefit of a guided “smart” needle that senses blood vessels, thereby dramatically reducing the risk of adverse events such as necrosis and blindness.

That is the goal of an experienced team composed of leading clinicians, academics, and researchers developing S³ Inject, a first-in-class safety innovation that has entered human trials.

“When physicians inject the fillers, they hope experience and technique will enable them to avoid adverse events,” Irina Erenburg, PhD, said during the virtual annual Masters of Aesthetics Symposium. “If they inadvertently hit a blood vessel, the filler can actually occlude that vessel and cause either an infarct of the skin or, in certain serious cases, blindness. This is a challenging adverse event that every injector is focused on avoiding. While hyaluronidase is used as a rescue [medication] in certain cases, the risk is real,” she added.

Vision abnormalities, including blindness, and necrosis are among the adverse events associated with dermal fillers that have been reported to the Food and Drug Administration.

S³ Inject is a sensing needle that can differentiate tissues such as fat, blood vessels, and muscle. Its proprietary algorithms provide immediate feedback via a micro LED light embedded in the needle hub. Results from recent human trials demonstrate that, as the needle tip passes through different biological tissues and fluids, “it senses changes in specific electrical properties and with that information sends a very precise signal to the needle hub,” said Dr. Erenburg, CEO and President of Waltham, Mass.–based Blossom Innovations, a company focused on developing early stage medical devices in dermatology. “With that information, the physician can make real-time treatment decisions.”

Currently, in order to determine if the needle is in a blood vessel, physicians pull back on the syringe and look for a flash of blood. “In speaking with physicians, the pull back technique has limitations, in part, because filler in the syringe can limit easy pull back to check the presence of a blood vessel,” she said. “Our needles provide an immediate response for a safer injection.”

Blossom Innovations has developed a proprietary manufacturing process that will initially target 27 gauge needles, but over time it plans to introduce multiple sizes, as well as cannulas.

“The physicians in our industry are committed to patient safety and they’re looking for better outcomes with a solution that does not impact their technique,” said Dr. Erenburg, who founded Blossom Innovations along with R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston; Dieter Manstein, MD, PhD, also at Massachusetts General Hospital; and Henry H.L. Chan, MD, PhD, of the Hong Kong Dermatology and Laser Center. During market research for S³ Inject, which was conducted with 15 leading injectors, thought leaders, and trend makers, the country’s leading injectors expressed strong interest in “solutions that allow them to provide additional safety for their patients and provide personal reassurance to the physician,” she said. “They definitely would want to train all their physicians and injectors on its use.”

As clinical testing continues, the company is preparing to submit data to the FDA’s Premarket Notification program, known as the 510(k) process. “Our intent is to create a scale-up manufacturing over the course of the coming year in time for our clearance, with a planned launch at the end of 2021,” Dr. Erenburg said. “Based on our clinical research and physician discussions, we are confident that S³ Inject is a breakthrough safety technology which will drive a better outcome for patients.”

Dr. Erenburg is an employee of Blossom Innovations.

[email protected]

In the very near future, clinicians injecting dermal fillers on the face will have the benefit of a guided “smart” needle that senses blood vessels, thereby dramatically reducing the risk of adverse events such as necrosis and blindness.

That is the goal of an experienced team composed of leading clinicians, academics, and researchers developing S³ Inject, a first-in-class safety innovation that has entered human trials.

“When physicians inject the fillers, they hope experience and technique will enable them to avoid adverse events,” Irina Erenburg, PhD, said during the virtual annual Masters of Aesthetics Symposium. “If they inadvertently hit a blood vessel, the filler can actually occlude that vessel and cause either an infarct of the skin or, in certain serious cases, blindness. This is a challenging adverse event that every injector is focused on avoiding. While hyaluronidase is used as a rescue [medication] in certain cases, the risk is real,” she added.

Vision abnormalities, including blindness, and necrosis are among the adverse events associated with dermal fillers that have been reported to the Food and Drug Administration.

S³ Inject is a sensing needle that can differentiate tissues such as fat, blood vessels, and muscle. Its proprietary algorithms provide immediate feedback via a micro LED light embedded in the needle hub. Results from recent human trials demonstrate that, as the needle tip passes through different biological tissues and fluids, “it senses changes in specific electrical properties and with that information sends a very precise signal to the needle hub,” said Dr. Erenburg, CEO and President of Waltham, Mass.–based Blossom Innovations, a company focused on developing early stage medical devices in dermatology. “With that information, the physician can make real-time treatment decisions.”

Currently, in order to determine if the needle is in a blood vessel, physicians pull back on the syringe and look for a flash of blood. “In speaking with physicians, the pull back technique has limitations, in part, because filler in the syringe can limit easy pull back to check the presence of a blood vessel,” she said. “Our needles provide an immediate response for a safer injection.”

Blossom Innovations has developed a proprietary manufacturing process that will initially target 27 gauge needles, but over time it plans to introduce multiple sizes, as well as cannulas.

“The physicians in our industry are committed to patient safety and they’re looking for better outcomes with a solution that does not impact their technique,” said Dr. Erenburg, who founded Blossom Innovations along with R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston; Dieter Manstein, MD, PhD, also at Massachusetts General Hospital; and Henry H.L. Chan, MD, PhD, of the Hong Kong Dermatology and Laser Center. During market research for S³ Inject, which was conducted with 15 leading injectors, thought leaders, and trend makers, the country’s leading injectors expressed strong interest in “solutions that allow them to provide additional safety for their patients and provide personal reassurance to the physician,” she said. “They definitely would want to train all their physicians and injectors on its use.”

As clinical testing continues, the company is preparing to submit data to the FDA’s Premarket Notification program, known as the 510(k) process. “Our intent is to create a scale-up manufacturing over the course of the coming year in time for our clearance, with a planned launch at the end of 2021,” Dr. Erenburg said. “Based on our clinical research and physician discussions, we are confident that S³ Inject is a breakthrough safety technology which will drive a better outcome for patients.”

Dr. Erenburg is an employee of Blossom Innovations.

[email protected]

The human growth hormone formulation somapacitan for adults with growth hormone deficiency was approved by the Food and Drug Administration on Sept. 1. The drug is injected once a week, while other FDA-approved human growth hormone formulations require daily jabs.

Somapacitan contains an albumin-binding element attached to the growth hormone, causing the reversible binding to albumin proteins in the body. This reduces clearance and increases the half-life of the hormone. The formulation has previous demonstrated safety and efficacy in children with growth hormone deficiency (J Clin Endocrinol Metab. 2020 Apr 1. doi: 10.1210/clinem/dgz310).

Growth hormone treatment can counter abdominal obesity, reduced lean body mass, fatigue, osteopenia, cardiovascular risks, and other manifestations of growth hormone deficiency in adults, but daily injections can be burdensome for patients. That makes long-acting versions attractive, but the lifelong nature of the treatment makes it important to characterize safety and tolerability.

The approval comes on the strength of a randomized, placebo-controlled phase 3 trial (REAL 1) of 300 adult patients in 17 countries with growth hormone deficiency (J Clin Endocrinol Metab. 2020 Apr 1. doi: 10.1210/clinem/dgaa049). Participants had either never received growth hormone treatment, or had stopped taking one at least 6 months before starting the trial. Subjects received once-weekly somapacitan, once-weekly placebo, or daily somatropin, which is FDA approved.

The primary endpoint was percentage change of truncal fat, which is regulated by growth hormone, and can lead to medical problems. After 34 weeks, subjects in the somapacitan group experienced a 1.06% decrease in truncal fat, compared with a 0.47% increase in the placebo group (P = .009) and a 2.23% decrease in the daily somatropin group.

After 34 weeks, a 52-week extension trial began. The somapacitan group continued on the drug and the placebo group was offered somapacitan. Patients on daily somatropin were randomized to continue daily treatment with somatropin or to switch to somapacitan.

At the end of the extension trial, those taking somapacitan for the full 86-week duration had an average reduction of 1.52% in truncal fat. After 86 weeks, the somapacitan and daily somatropin groups had similar values for percentage change in visceral fat, lean body mass, or appendicular skeletal muscle mass.

Common side effects of somapacitan were back pain, joint paint, indigestion, a sleep disorder, dizziness, tonsillitis, swelling in the arms or lower legs, vomiting, adrenal insufficiency, hypertension, increase in blood creatine phosphokinase, weight increase, and anemia.

Somapacitan, marketed as Sogroya by Novo Nordisk, is contraindicated in patients with an allergy to the drug, as well as those with an active malignancy, diabetic eye disease where increases in blood sugars could lead to retinal damage, acute critical illness, or acute respiratory failure.

The FDA recommends that providers perform an eye examination before drug initiation, as well as periodically while the patient is taking the drug, to rule out preexisting papilledema. This could be a sign of intracranial hypertension, which could be caused or worsened by growth hormones.

The human growth hormone formulation somapacitan for adults with growth hormone deficiency was approved by the Food and Drug Administration on Sept. 1. The drug is injected once a week, while other FDA-approved human growth hormone formulations require daily jabs.

Somapacitan contains an albumin-binding element attached to the growth hormone, causing the reversible binding to albumin proteins in the body. This reduces clearance and increases the half-life of the hormone. The formulation has previous demonstrated safety and efficacy in children with growth hormone deficiency (J Clin Endocrinol Metab. 2020 Apr 1. doi: 10.1210/clinem/dgz310).

Growth hormone treatment can counter abdominal obesity, reduced lean body mass, fatigue, osteopenia, cardiovascular risks, and other manifestations of growth hormone deficiency in adults, but daily injections can be burdensome for patients. That makes long-acting versions attractive, but the lifelong nature of the treatment makes it important to characterize safety and tolerability.

The approval comes on the strength of a randomized, placebo-controlled phase 3 trial (REAL 1) of 300 adult patients in 17 countries with growth hormone deficiency (J Clin Endocrinol Metab. 2020 Apr 1. doi: 10.1210/clinem/dgaa049). Participants had either never received growth hormone treatment, or had stopped taking one at least 6 months before starting the trial. Subjects received once-weekly somapacitan, once-weekly placebo, or daily somatropin, which is FDA approved.

The primary endpoint was percentage change of truncal fat, which is regulated by growth hormone, and can lead to medical problems. After 34 weeks, subjects in the somapacitan group experienced a 1.06% decrease in truncal fat, compared with a 0.47% increase in the placebo group (P = .009) and a 2.23% decrease in the daily somatropin group.

After 34 weeks, a 52-week extension trial began. The somapacitan group continued on the drug and the placebo group was offered somapacitan. Patients on daily somatropin were randomized to continue daily treatment with somatropin or to switch to somapacitan.

At the end of the extension trial, those taking somapacitan for the full 86-week duration had an average reduction of 1.52% in truncal fat. After 86 weeks, the somapacitan and daily somatropin groups had similar values for percentage change in visceral fat, lean body mass, or appendicular skeletal muscle mass.

Common side effects of somapacitan were back pain, joint paint, indigestion, a sleep disorder, dizziness, tonsillitis, swelling in the arms or lower legs, vomiting, adrenal insufficiency, hypertension, increase in blood creatine phosphokinase, weight increase, and anemia.

Somapacitan, marketed as Sogroya by Novo Nordisk, is contraindicated in patients with an allergy to the drug, as well as those with an active malignancy, diabetic eye disease where increases in blood sugars could lead to retinal damage, acute critical illness, or acute respiratory failure.

The FDA recommends that providers perform an eye examination before drug initiation, as well as periodically while the patient is taking the drug, to rule out preexisting papilledema. This could be a sign of intracranial hypertension, which could be caused or worsened by growth hormones.

The human growth hormone formulation somapacitan for adults with growth hormone deficiency was approved by the Food and Drug Administration on Sept. 1. The drug is injected once a week, while other FDA-approved human growth hormone formulations require daily jabs.

Somapacitan contains an albumin-binding element attached to the growth hormone, causing the reversible binding to albumin proteins in the body. This reduces clearance and increases the half-life of the hormone. The formulation has previous demonstrated safety and efficacy in children with growth hormone deficiency (J Clin Endocrinol Metab. 2020 Apr 1. doi: 10.1210/clinem/dgz310).

Growth hormone treatment can counter abdominal obesity, reduced lean body mass, fatigue, osteopenia, cardiovascular risks, and other manifestations of growth hormone deficiency in adults, but daily injections can be burdensome for patients. That makes long-acting versions attractive, but the lifelong nature of the treatment makes it important to characterize safety and tolerability.

The approval comes on the strength of a randomized, placebo-controlled phase 3 trial (REAL 1) of 300 adult patients in 17 countries with growth hormone deficiency (J Clin Endocrinol Metab. 2020 Apr 1. doi: 10.1210/clinem/dgaa049). Participants had either never received growth hormone treatment, or had stopped taking one at least 6 months before starting the trial. Subjects received once-weekly somapacitan, once-weekly placebo, or daily somatropin, which is FDA approved.

The primary endpoint was percentage change of truncal fat, which is regulated by growth hormone, and can lead to medical problems. After 34 weeks, subjects in the somapacitan group experienced a 1.06% decrease in truncal fat, compared with a 0.47% increase in the placebo group (P = .009) and a 2.23% decrease in the daily somatropin group.

After 34 weeks, a 52-week extension trial began. The somapacitan group continued on the drug and the placebo group was offered somapacitan. Patients on daily somatropin were randomized to continue daily treatment with somatropin or to switch to somapacitan.

At the end of the extension trial, those taking somapacitan for the full 86-week duration had an average reduction of 1.52% in truncal fat. After 86 weeks, the somapacitan and daily somatropin groups had similar values for percentage change in visceral fat, lean body mass, or appendicular skeletal muscle mass.

Common side effects of somapacitan were back pain, joint paint, indigestion, a sleep disorder, dizziness, tonsillitis, swelling in the arms or lower legs, vomiting, adrenal insufficiency, hypertension, increase in blood creatine phosphokinase, weight increase, and anemia.

Somapacitan, marketed as Sogroya by Novo Nordisk, is contraindicated in patients with an allergy to the drug, as well as those with an active malignancy, diabetic eye disease where increases in blood sugars could lead to retinal damage, acute critical illness, or acute respiratory failure.

The FDA recommends that providers perform an eye examination before drug initiation, as well as periodically while the patient is taking the drug, to rule out preexisting papilledema. This could be a sign of intracranial hypertension, which could be caused or worsened by growth hormones.