MDedge Endocrinology

Omecamtiv mecarbil, a member of the novel myotropic drug class that improves cardiac performance, safely produced a significant but modest improvement in heart failure events or cardiovascular death in a pivotal trial with HFrEF patients, leaving experts unsure about the role this drug could have on top of an already crowded list of four first-line drug classes for this condition.

“It remains to be investigated and discussed where omecamtiv mecarbil fits in” the overall approach to treating patients with heart failure with reduced ejection fraction (HFrEF), commented Paul Heidenreich, MD, designated discussant for the report at the virtual scientific sessions of the American Heart Association.

Room for a fifth HFrEF drug?

In addition to the limited benefit, another question raised by the trial is how OM would perform when used on top of what is now considered standard, quadruple therapy for most HFrEF patients: a beta-blocker, a mineralocorticoid receptor antagonist, sacubitril-valsartan (Entresto), and an agent from the sodium glucose co-transporter 2 (SGLT2) inhibitor class, specifically dapagliflozin (Farxiga) or empagliflozin (Jardiance). During the period when the new OM trial was run, 2017-2019, the SGLT2 inhibitors had not yet been established as a key part of standard HFrEF treatment, and hence fewer than 3% of enrolled patients were on one of these drugs.

Because of this evidence gap, OM “can’t be across the board a fifth drug on top of standard treatment,” based on the new results, cautioned Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University School of Medicine.

The positives of omecamtiv mercarbil

But in addition to its positive result in the GALACTIC-HF trial, treatment with OM showed other attractive characteristics in a study that treated a wide spectrum of 4,120 patients with HFrEF as well as including 4,112 patients randomized to placebo. Most notably, OM had a very clean safety profile, with adverse event rates similar to placebo patients across all adverse event subtypes, as well as causing no drop in blood pressure and actually an average 2.0–mm Hg increase in systolic blood pressure, no increase in potassium, no apparent impact on renal function, and a small but significant decline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) compared with placebo.

This coupled with the novel mechanism of action of OM – direct augmentation of cardiac sarcomere function by increasing myosin attachment to actin – suggests that OM can be safely added on top of existing HFrEF treatment to provide an unique and incremental benefit.

“Other heart failure drugs [like beta-blockers and sacubitril-valsartan] lower blood pressure, so what can happen is that clinicians run out of room to add full dosages” when patients’ pressures fall too low, commented Gregory D. Lewis, MD, head of Heart Failure at Massachusetts General Hospital in Boston. He is principle investigator for another OM trial, METEORIC-HF, which is examining the possible impact of the drug on exercise capacity in a randomized study with about 270 HFrEF patients.

If the METEORIC-HF results can could confirm some of the GALACTIC-HF results that suggested improvements in patient function, the combined data could potentially lead to regulatory approval for U.S. marketing of the drug, Dr. Lewis suggested. Results from that study are expected in 2021, he said in an interview.

The GALACTIC-HF results hinted at possible functional improvement after 24 weeks on treatment among patients who required hospitalization as measured by the Kansas City Cardiomyopathy Questionnaire, which measures quality life. However, this difference failed to meet the study’s prespecified definition of a significant effect.

Another intriguing suggestion of focused benefit was in patients with a left ventricular ejection fraction at or below the median in GALACTIC-HF of 28%. In that subgroup, OM treatment was linked with a significant 16% relative reduction in the primary endpoint compared with placebo, while it had no significant effect in the other 50% of patients with higher ejection fractions. (The maximum left ventricular ejection fraction for enrollment was 35%.) This apparent subgroup interaction was statistically significant, reported Dr. Teerlink, a professor of medicine at the University of California, San Francisco, and director of Heart Failure at the San Francisco V.A. Medical Center.

Further analysis of the study data “will provide greater insight into subgroups who may demonstrate greater benefit, such as patients with lower ejection fraction in whom improving cardiac function may have a greater role,” he said. The idea that a drug that improves myocyte function at the molecular level could especially benefit patients with the lowest ejection fractions is “biologically plausible,” Dr. Teerlink said.

This scenario looks reasonable, and could make OM something of a niche drug for at least the near term, said Dr. Mann.

The world’s first myotropic drug

Possibly the most notable aspect of GALACTIC-HF is that it proved the efficacy, modest though it was, of a novel drug mechanism that fulfills a decades-long quest of heart failure researchers: a safe way to improve the heart’s pumping action.

“For years, the heart failure community struggled with treatment to improve cardiac performance, but invariably it ended in disaster by worsening cardiac deaths,” problems that led to abandonment of early inotropic drugs more than a generation ago, noted Dr. Mann.

But a more nuanced approach to inotropic agents recently has emerged from Dr. Teerlink and his associates, built on the premise that the dangers seen years ago related to the calcium modulations they caused. Their new paradigm is that the dangers of these “calcitropic” agents can be sidestepped with different agents that either mediate their effects via myosin, the myotropes like OM, or mitochondrial effects from mitotropic drugs.

The inotrope debacle from the 1990s made that drug-class name “a dirty word that causes fear and loathing in the heart failure community,” observed Dr. Mann. While the term myotrope has not yet really caught on, “If omecamtiv mecarbil starts getting used in routine practice, then I think you’ll start seeing uptake of the term myotrope,” he predicted.

GALACTIC-HF was sponsored by Amgen, Cytokinetics, and Servier, the companies developing omecamtiv mecarbil. Dr. Teerlink has received research support from and been a consultant to Amgen, Cytokinetics, and Servier, as well as Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Merck, and Novartis. Dr. Heidenreich had no disclosures. Dr. Mann is on a steering committee for a trial sponsored by Novartis and has no other commercial disclosures. Dr. Lewis is principal investigator for a trial of omecamtiv mecarbil and has no other commercial disclosures.

mzoler@mdedge.com

On Twitter @mitchelzoler

Omecamtiv mecarbil, a member of the novel myotropic drug class that improves cardiac performance, safely produced a significant but modest improvement in heart failure events or cardiovascular death in a pivotal trial with HFrEF patients, leaving experts unsure about the role this drug could have on top of an already crowded list of four first-line drug classes for this condition.

“It remains to be investigated and discussed where omecamtiv mecarbil fits in” the overall approach to treating patients with heart failure with reduced ejection fraction (HFrEF), commented Paul Heidenreich, MD, designated discussant for the report at the virtual scientific sessions of the American Heart Association.

Room for a fifth HFrEF drug?

In addition to the limited benefit, another question raised by the trial is how OM would perform when used on top of what is now considered standard, quadruple therapy for most HFrEF patients: a beta-blocker, a mineralocorticoid receptor antagonist, sacubitril-valsartan (Entresto), and an agent from the sodium glucose co-transporter 2 (SGLT2) inhibitor class, specifically dapagliflozin (Farxiga) or empagliflozin (Jardiance). During the period when the new OM trial was run, 2017-2019, the SGLT2 inhibitors had not yet been established as a key part of standard HFrEF treatment, and hence fewer than 3% of enrolled patients were on one of these drugs.

Because of this evidence gap, OM “can’t be across the board a fifth drug on top of standard treatment,” based on the new results, cautioned Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University School of Medicine.

The positives of omecamtiv mercarbil

But in addition to its positive result in the GALACTIC-HF trial, treatment with OM showed other attractive characteristics in a study that treated a wide spectrum of 4,120 patients with HFrEF as well as including 4,112 patients randomized to placebo. Most notably, OM had a very clean safety profile, with adverse event rates similar to placebo patients across all adverse event subtypes, as well as causing no drop in blood pressure and actually an average 2.0–mm Hg increase in systolic blood pressure, no increase in potassium, no apparent impact on renal function, and a small but significant decline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) compared with placebo.

This coupled with the novel mechanism of action of OM – direct augmentation of cardiac sarcomere function by increasing myosin attachment to actin – suggests that OM can be safely added on top of existing HFrEF treatment to provide an unique and incremental benefit.

“Other heart failure drugs [like beta-blockers and sacubitril-valsartan] lower blood pressure, so what can happen is that clinicians run out of room to add full dosages” when patients’ pressures fall too low, commented Gregory D. Lewis, MD, head of Heart Failure at Massachusetts General Hospital in Boston. He is principle investigator for another OM trial, METEORIC-HF, which is examining the possible impact of the drug on exercise capacity in a randomized study with about 270 HFrEF patients.

If the METEORIC-HF results can could confirm some of the GALACTIC-HF results that suggested improvements in patient function, the combined data could potentially lead to regulatory approval for U.S. marketing of the drug, Dr. Lewis suggested. Results from that study are expected in 2021, he said in an interview.

The GALACTIC-HF results hinted at possible functional improvement after 24 weeks on treatment among patients who required hospitalization as measured by the Kansas City Cardiomyopathy Questionnaire, which measures quality life. However, this difference failed to meet the study’s prespecified definition of a significant effect.

Another intriguing suggestion of focused benefit was in patients with a left ventricular ejection fraction at or below the median in GALACTIC-HF of 28%. In that subgroup, OM treatment was linked with a significant 16% relative reduction in the primary endpoint compared with placebo, while it had no significant effect in the other 50% of patients with higher ejection fractions. (The maximum left ventricular ejection fraction for enrollment was 35%.) This apparent subgroup interaction was statistically significant, reported Dr. Teerlink, a professor of medicine at the University of California, San Francisco, and director of Heart Failure at the San Francisco V.A. Medical Center.

Further analysis of the study data “will provide greater insight into subgroups who may demonstrate greater benefit, such as patients with lower ejection fraction in whom improving cardiac function may have a greater role,” he said. The idea that a drug that improves myocyte function at the molecular level could especially benefit patients with the lowest ejection fractions is “biologically plausible,” Dr. Teerlink said.

This scenario looks reasonable, and could make OM something of a niche drug for at least the near term, said Dr. Mann.

The world’s first myotropic drug

Possibly the most notable aspect of GALACTIC-HF is that it proved the efficacy, modest though it was, of a novel drug mechanism that fulfills a decades-long quest of heart failure researchers: a safe way to improve the heart’s pumping action.

“For years, the heart failure community struggled with treatment to improve cardiac performance, but invariably it ended in disaster by worsening cardiac deaths,” problems that led to abandonment of early inotropic drugs more than a generation ago, noted Dr. Mann.

But a more nuanced approach to inotropic agents recently has emerged from Dr. Teerlink and his associates, built on the premise that the dangers seen years ago related to the calcium modulations they caused. Their new paradigm is that the dangers of these “calcitropic” agents can be sidestepped with different agents that either mediate their effects via myosin, the myotropes like OM, or mitochondrial effects from mitotropic drugs.

The inotrope debacle from the 1990s made that drug-class name “a dirty word that causes fear and loathing in the heart failure community,” observed Dr. Mann. While the term myotrope has not yet really caught on, “If omecamtiv mecarbil starts getting used in routine practice, then I think you’ll start seeing uptake of the term myotrope,” he predicted.

GALACTIC-HF was sponsored by Amgen, Cytokinetics, and Servier, the companies developing omecamtiv mecarbil. Dr. Teerlink has received research support from and been a consultant to Amgen, Cytokinetics, and Servier, as well as Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Merck, and Novartis. Dr. Heidenreich had no disclosures. Dr. Mann is on a steering committee for a trial sponsored by Novartis and has no other commercial disclosures. Dr. Lewis is principal investigator for a trial of omecamtiv mecarbil and has no other commercial disclosures.

mzoler@mdedge.com

On Twitter @mitchelzoler

Omecamtiv mecarbil, a member of the novel myotropic drug class that improves cardiac performance, safely produced a significant but modest improvement in heart failure events or cardiovascular death in a pivotal trial with HFrEF patients, leaving experts unsure about the role this drug could have on top of an already crowded list of four first-line drug classes for this condition.

“It remains to be investigated and discussed where omecamtiv mecarbil fits in” the overall approach to treating patients with heart failure with reduced ejection fraction (HFrEF), commented Paul Heidenreich, MD, designated discussant for the report at the virtual scientific sessions of the American Heart Association.

Room for a fifth HFrEF drug?

In addition to the limited benefit, another question raised by the trial is how OM would perform when used on top of what is now considered standard, quadruple therapy for most HFrEF patients: a beta-blocker, a mineralocorticoid receptor antagonist, sacubitril-valsartan (Entresto), and an agent from the sodium glucose co-transporter 2 (SGLT2) inhibitor class, specifically dapagliflozin (Farxiga) or empagliflozin (Jardiance). During the period when the new OM trial was run, 2017-2019, the SGLT2 inhibitors had not yet been established as a key part of standard HFrEF treatment, and hence fewer than 3% of enrolled patients were on one of these drugs.

Because of this evidence gap, OM “can’t be across the board a fifth drug on top of standard treatment,” based on the new results, cautioned Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University School of Medicine.

The positives of omecamtiv mercarbil

But in addition to its positive result in the GALACTIC-HF trial, treatment with OM showed other attractive characteristics in a study that treated a wide spectrum of 4,120 patients with HFrEF as well as including 4,112 patients randomized to placebo. Most notably, OM had a very clean safety profile, with adverse event rates similar to placebo patients across all adverse event subtypes, as well as causing no drop in blood pressure and actually an average 2.0–mm Hg increase in systolic blood pressure, no increase in potassium, no apparent impact on renal function, and a small but significant decline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) compared with placebo.

This coupled with the novel mechanism of action of OM – direct augmentation of cardiac sarcomere function by increasing myosin attachment to actin – suggests that OM can be safely added on top of existing HFrEF treatment to provide an unique and incremental benefit.

“Other heart failure drugs [like beta-blockers and sacubitril-valsartan] lower blood pressure, so what can happen is that clinicians run out of room to add full dosages” when patients’ pressures fall too low, commented Gregory D. Lewis, MD, head of Heart Failure at Massachusetts General Hospital in Boston. He is principle investigator for another OM trial, METEORIC-HF, which is examining the possible impact of the drug on exercise capacity in a randomized study with about 270 HFrEF patients.

If the METEORIC-HF results can could confirm some of the GALACTIC-HF results that suggested improvements in patient function, the combined data could potentially lead to regulatory approval for U.S. marketing of the drug, Dr. Lewis suggested. Results from that study are expected in 2021, he said in an interview.

The GALACTIC-HF results hinted at possible functional improvement after 24 weeks on treatment among patients who required hospitalization as measured by the Kansas City Cardiomyopathy Questionnaire, which measures quality life. However, this difference failed to meet the study’s prespecified definition of a significant effect.

Another intriguing suggestion of focused benefit was in patients with a left ventricular ejection fraction at or below the median in GALACTIC-HF of 28%. In that subgroup, OM treatment was linked with a significant 16% relative reduction in the primary endpoint compared with placebo, while it had no significant effect in the other 50% of patients with higher ejection fractions. (The maximum left ventricular ejection fraction for enrollment was 35%.) This apparent subgroup interaction was statistically significant, reported Dr. Teerlink, a professor of medicine at the University of California, San Francisco, and director of Heart Failure at the San Francisco V.A. Medical Center.

Further analysis of the study data “will provide greater insight into subgroups who may demonstrate greater benefit, such as patients with lower ejection fraction in whom improving cardiac function may have a greater role,” he said. The idea that a drug that improves myocyte function at the molecular level could especially benefit patients with the lowest ejection fractions is “biologically plausible,” Dr. Teerlink said.

This scenario looks reasonable, and could make OM something of a niche drug for at least the near term, said Dr. Mann.

The world’s first myotropic drug

Possibly the most notable aspect of GALACTIC-HF is that it proved the efficacy, modest though it was, of a novel drug mechanism that fulfills a decades-long quest of heart failure researchers: a safe way to improve the heart’s pumping action.

“For years, the heart failure community struggled with treatment to improve cardiac performance, but invariably it ended in disaster by worsening cardiac deaths,” problems that led to abandonment of early inotropic drugs more than a generation ago, noted Dr. Mann.

But a more nuanced approach to inotropic agents recently has emerged from Dr. Teerlink and his associates, built on the premise that the dangers seen years ago related to the calcium modulations they caused. Their new paradigm is that the dangers of these “calcitropic” agents can be sidestepped with different agents that either mediate their effects via myosin, the myotropes like OM, or mitochondrial effects from mitotropic drugs.

The inotrope debacle from the 1990s made that drug-class name “a dirty word that causes fear and loathing in the heart failure community,” observed Dr. Mann. While the term myotrope has not yet really caught on, “If omecamtiv mecarbil starts getting used in routine practice, then I think you’ll start seeing uptake of the term myotrope,” he predicted.

GALACTIC-HF was sponsored by Amgen, Cytokinetics, and Servier, the companies developing omecamtiv mecarbil. Dr. Teerlink has received research support from and been a consultant to Amgen, Cytokinetics, and Servier, as well as Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Merck, and Novartis. Dr. Heidenreich had no disclosures. Dr. Mann is on a steering committee for a trial sponsored by Novartis and has no other commercial disclosures. Dr. Lewis is principal investigator for a trial of omecamtiv mecarbil and has no other commercial disclosures.

mzoler@mdedge.com

On Twitter @mitchelzoler

A panel convened by The Lancet has published a comprehensive report calling for major initiatives to improve diabetes prevention and care around the world.

The article was published online Nov. 12, just ahead of World Diabetes Day.

Of the 463 million people with diabetes worldwide in 2019, 80% live in low- and middle-income countries. The condition reduces life expectancy in middle-aged adults by 4-10 years, including increasing the risk of death from cardiovascular disease, kidney disease, and cancer by up to threefold. It is also a leading cause of nontraumatic amputation and blindness.

Use of evidence-based interventions, if implemented and managed properly, could prevent thousands of deaths globally every day, stressed the commission.

“There is an enormous amount of knowledge that we have amassed over the years. We need good preventive care and we need to ensure that diabetes patients, once diagnosed, have good continuous care. There is an urgent need for decision-makers, policymakers, and payers to make things happen,” the leader of the multidisciplinary commission, Juliana C.N. Chan, MBChB, MD, said in an interview.

And now diabetes has emerged as a major risk factor for death from COVID-19, particularly in the setting of inadequate glycemic control.

“COVID-19 has exposed the vulnerability of individuals with diabetes,” said Dr. Chan, of the Hong Kong Institute of Diabetes and Obesity. “We should use the pandemic as an opportunity to implement solutions.”
 

Physician education key, trickling down to field workers and patients

First on the agenda, she says, should be “physician education. There are many primary care providers and internal medicine physicians whose knowledge needs to be updated.”

“Then doctors need to transfer this information to other people, such as nurses and community field workers. We cannot just rely on doctors; we need to train nonmedics” so that knowledge about how to prevent, treat, and manage diabetes long term is communicated right down the health care chain, she explained.

“They need to know how to look at people’s eyes and feet, how to do blood and urine tests, and how to collect data. Then they need to educate patients on what they should be doing, on how to practice self-care,” she added.

“We need to change our way of thinking, redesign clinic flow and how you build a team. And those care teams need to know how to collect data, and then use that data to monitor patients and to stratify individual risk, to ensure that what has been said has been done, as well as to inform practice and policies” through, for example, the establishment of diabetes registers.

The focus needs to be on “lifelong integrated care, the right treatment at the right time,” she emphasized. History-taking, clinical and laboratory assessments, as well as monitoring of macrovascular and microvascular complications, comorbidities, and medications, are all key.

Just a few simple things, if properly implemented, could make a big difference, Dr. Chan stressed.

For example, implementing a structured lifestyle intervention and use of metformin can each prevent or delay type 2 diabetes in individuals with impaired glucose tolerance by 30%-50%, and sustained weight reduction in patients with obesity by 15 kg (33 lb) or more can induce remission of type 2 diabetes for up to 2 years.

And there are plenty of medications that are “very affordable even in low- and middle-income countries” to treat diabetes and associated risk factors, including metformin, “statins, and RAS inhibitors,” she noted.

For instance, the 10 low- and middle-income countries with the greatest burden of diabetes (China, India, Brazil, Mexico, Indonesia, Egypt, Pakistan, Bangladesh, Turkey, Thailand) account for 217 million cases of type 2 diabetes, representing nearly 50% of all diabetes cases.

The commission estimated that 3.2 million of these individuals would die in 3 years if not treated, with 1.3 million of these deaths due to cardiovascular disease.

By reducing hemoglobin A1c, blood pressure, and LDL-cholesterol through achieving a diagnosis rate of 50%, ensuring access to essential medicines in at least 70% of patients, and with a support system to sustain reductions in these risk factors over 3 years, up to 800,000 premature deaths could be avoided.
 

People with type 1 diabetes dying; WHO launches initiative

In an accompanying commentary (2020 Nov 12. doi: 10.1016/S0140-6736[20]32378-3), Katie Dain, chief executive officer of the Noncommunicable Diseases (NCD) Alliance, points out that only half of people living with diabetes around the world – and just one in seven in Africa – have reliable access to insulin.

“Lots of people with type 1 diabetes are still dying due to lack of insulin,” Dr. Chan said in an interview. “We need to elevate basic care to intermediate and ensure that basal-bolus insulin and glucose-monitoring tools are available and that patients are trained in self-care. In that way, 80% of type 1 diabetes deaths could be prevented.”

Ms. 3Dain agrees, stressing, “Political rhetoric and commitments have yet to translate into sufficient and sustainable action for people living with diabetes worldwide, and particularly for those in [low- and middle-income countries].”

The Lancet Commission document also emphasizes the importance of support for pregnant women with diabetes and attention to the psychosocial needs of people with diabetes.

And it stresses society-, population-, and community-based strategies for type 2 diabetes prevention including health awareness programs, food policies, and broad use of nonphysician personnel to deliver diabetes prevention efforts.

In tandem with World Diabetes Day, the World Health Organization will announce the development of the WHO Global Diabetes Compact, which will be launched in April 2021.

This will aim to implement the commission’s recommendations through partnerships with governments, care providers, patient advocates, and nongovernmental organizations.

Together, they will “support countries to mobilize resources and accelerate structural transformations, which will enable the scale-up of access to essential diabetes medicines and technologies, inclusion of diagnosis and treatment of diabetes in primary health care and universal health coverage packages, and reduction of major population-level diabetes risk factors such as obesity,” according to another Lancet editorial accompanying the report.

“The evidence-base for improving diabetes prevention and care is strong. The question now for diabetes advocates is how to achieve the comprehensive, systems-level change needed to translate this evidence into action.”

Dr. Chan has reported receiving grants from AstraZeneca, Lilly, Lee Powder, Hua Medicine, and Qualigenics, as well as grants and personal fees from Bayer, Boehringer Ingelheim, Sanofi, Novartis, Merck, and MSD outside the submitted work. She has reported being the chief executive officer (pro bono) of the Asia Diabetes Foundation and a cofounder of GemVCare. She also holds a patent for genetic markers for diabetes and its complications. Ms. Dain has reported no relevant financial relationships.
 

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

A panel convened by The Lancet has published a comprehensive report calling for major initiatives to improve diabetes prevention and care around the world.

The article was published online Nov. 12, just ahead of World Diabetes Day.

Of the 463 million people with diabetes worldwide in 2019, 80% live in low- and middle-income countries. The condition reduces life expectancy in middle-aged adults by 4-10 years, including increasing the risk of death from cardiovascular disease, kidney disease, and cancer by up to threefold. It is also a leading cause of nontraumatic amputation and blindness.

Use of evidence-based interventions, if implemented and managed properly, could prevent thousands of deaths globally every day, stressed the commission.

“There is an enormous amount of knowledge that we have amassed over the years. We need good preventive care and we need to ensure that diabetes patients, once diagnosed, have good continuous care. There is an urgent need for decision-makers, policymakers, and payers to make things happen,” the leader of the multidisciplinary commission, Juliana C.N. Chan, MBChB, MD, said in an interview.

And now diabetes has emerged as a major risk factor for death from COVID-19, particularly in the setting of inadequate glycemic control.

“COVID-19 has exposed the vulnerability of individuals with diabetes,” said Dr. Chan, of the Hong Kong Institute of Diabetes and Obesity. “We should use the pandemic as an opportunity to implement solutions.”
 

Physician education key, trickling down to field workers and patients

First on the agenda, she says, should be “physician education. There are many primary care providers and internal medicine physicians whose knowledge needs to be updated.”

“Then doctors need to transfer this information to other people, such as nurses and community field workers. We cannot just rely on doctors; we need to train nonmedics” so that knowledge about how to prevent, treat, and manage diabetes long term is communicated right down the health care chain, she explained.

“They need to know how to look at people’s eyes and feet, how to do blood and urine tests, and how to collect data. Then they need to educate patients on what they should be doing, on how to practice self-care,” she added.

“We need to change our way of thinking, redesign clinic flow and how you build a team. And those care teams need to know how to collect data, and then use that data to monitor patients and to stratify individual risk, to ensure that what has been said has been done, as well as to inform practice and policies” through, for example, the establishment of diabetes registers.

The focus needs to be on “lifelong integrated care, the right treatment at the right time,” she emphasized. History-taking, clinical and laboratory assessments, as well as monitoring of macrovascular and microvascular complications, comorbidities, and medications, are all key.

Just a few simple things, if properly implemented, could make a big difference, Dr. Chan stressed.

For example, implementing a structured lifestyle intervention and use of metformin can each prevent or delay type 2 diabetes in individuals with impaired glucose tolerance by 30%-50%, and sustained weight reduction in patients with obesity by 15 kg (33 lb) or more can induce remission of type 2 diabetes for up to 2 years.

And there are plenty of medications that are “very affordable even in low- and middle-income countries” to treat diabetes and associated risk factors, including metformin, “statins, and RAS inhibitors,” she noted.

For instance, the 10 low- and middle-income countries with the greatest burden of diabetes (China, India, Brazil, Mexico, Indonesia, Egypt, Pakistan, Bangladesh, Turkey, Thailand) account for 217 million cases of type 2 diabetes, representing nearly 50% of all diabetes cases.

The commission estimated that 3.2 million of these individuals would die in 3 years if not treated, with 1.3 million of these deaths due to cardiovascular disease.

By reducing hemoglobin A1c, blood pressure, and LDL-cholesterol through achieving a diagnosis rate of 50%, ensuring access to essential medicines in at least 70% of patients, and with a support system to sustain reductions in these risk factors over 3 years, up to 800,000 premature deaths could be avoided.
 

People with type 1 diabetes dying; WHO launches initiative

In an accompanying commentary (2020 Nov 12. doi: 10.1016/S0140-6736[20]32378-3), Katie Dain, chief executive officer of the Noncommunicable Diseases (NCD) Alliance, points out that only half of people living with diabetes around the world – and just one in seven in Africa – have reliable access to insulin.

“Lots of people with type 1 diabetes are still dying due to lack of insulin,” Dr. Chan said in an interview. “We need to elevate basic care to intermediate and ensure that basal-bolus insulin and glucose-monitoring tools are available and that patients are trained in self-care. In that way, 80% of type 1 diabetes deaths could be prevented.”

Ms. 3Dain agrees, stressing, “Political rhetoric and commitments have yet to translate into sufficient and sustainable action for people living with diabetes worldwide, and particularly for those in [low- and middle-income countries].”

The Lancet Commission document also emphasizes the importance of support for pregnant women with diabetes and attention to the psychosocial needs of people with diabetes.

And it stresses society-, population-, and community-based strategies for type 2 diabetes prevention including health awareness programs, food policies, and broad use of nonphysician personnel to deliver diabetes prevention efforts.

In tandem with World Diabetes Day, the World Health Organization will announce the development of the WHO Global Diabetes Compact, which will be launched in April 2021.

This will aim to implement the commission’s recommendations through partnerships with governments, care providers, patient advocates, and nongovernmental organizations.

Together, they will “support countries to mobilize resources and accelerate structural transformations, which will enable the scale-up of access to essential diabetes medicines and technologies, inclusion of diagnosis and treatment of diabetes in primary health care and universal health coverage packages, and reduction of major population-level diabetes risk factors such as obesity,” according to another Lancet editorial accompanying the report.

“The evidence-base for improving diabetes prevention and care is strong. The question now for diabetes advocates is how to achieve the comprehensive, systems-level change needed to translate this evidence into action.”

Dr. Chan has reported receiving grants from AstraZeneca, Lilly, Lee Powder, Hua Medicine, and Qualigenics, as well as grants and personal fees from Bayer, Boehringer Ingelheim, Sanofi, Novartis, Merck, and MSD outside the submitted work. She has reported being the chief executive officer (pro bono) of the Asia Diabetes Foundation and a cofounder of GemVCare. She also holds a patent for genetic markers for diabetes and its complications. Ms. Dain has reported no relevant financial relationships.
 

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

A panel convened by The Lancet has published a comprehensive report calling for major initiatives to improve diabetes prevention and care around the world.

The article was published online Nov. 12, just ahead of World Diabetes Day.

Of the 463 million people with diabetes worldwide in 2019, 80% live in low- and middle-income countries. The condition reduces life expectancy in middle-aged adults by 4-10 years, including increasing the risk of death from cardiovascular disease, kidney disease, and cancer by up to threefold. It is also a leading cause of nontraumatic amputation and blindness.

Use of evidence-based interventions, if implemented and managed properly, could prevent thousands of deaths globally every day, stressed the commission.

“There is an enormous amount of knowledge that we have amassed over the years. We need good preventive care and we need to ensure that diabetes patients, once diagnosed, have good continuous care. There is an urgent need for decision-makers, policymakers, and payers to make things happen,” the leader of the multidisciplinary commission, Juliana C.N. Chan, MBChB, MD, said in an interview.

And now diabetes has emerged as a major risk factor for death from COVID-19, particularly in the setting of inadequate glycemic control.

“COVID-19 has exposed the vulnerability of individuals with diabetes,” said Dr. Chan, of the Hong Kong Institute of Diabetes and Obesity. “We should use the pandemic as an opportunity to implement solutions.”
 

Physician education key, trickling down to field workers and patients

First on the agenda, she says, should be “physician education. There are many primary care providers and internal medicine physicians whose knowledge needs to be updated.”

“Then doctors need to transfer this information to other people, such as nurses and community field workers. We cannot just rely on doctors; we need to train nonmedics” so that knowledge about how to prevent, treat, and manage diabetes long term is communicated right down the health care chain, she explained.

“They need to know how to look at people’s eyes and feet, how to do blood and urine tests, and how to collect data. Then they need to educate patients on what they should be doing, on how to practice self-care,” she added.

“We need to change our way of thinking, redesign clinic flow and how you build a team. And those care teams need to know how to collect data, and then use that data to monitor patients and to stratify individual risk, to ensure that what has been said has been done, as well as to inform practice and policies” through, for example, the establishment of diabetes registers.

The focus needs to be on “lifelong integrated care, the right treatment at the right time,” she emphasized. History-taking, clinical and laboratory assessments, as well as monitoring of macrovascular and microvascular complications, comorbidities, and medications, are all key.

Just a few simple things, if properly implemented, could make a big difference, Dr. Chan stressed.

For example, implementing a structured lifestyle intervention and use of metformin can each prevent or delay type 2 diabetes in individuals with impaired glucose tolerance by 30%-50%, and sustained weight reduction in patients with obesity by 15 kg (33 lb) or more can induce remission of type 2 diabetes for up to 2 years.

And there are plenty of medications that are “very affordable even in low- and middle-income countries” to treat diabetes and associated risk factors, including metformin, “statins, and RAS inhibitors,” she noted.

For instance, the 10 low- and middle-income countries with the greatest burden of diabetes (China, India, Brazil, Mexico, Indonesia, Egypt, Pakistan, Bangladesh, Turkey, Thailand) account for 217 million cases of type 2 diabetes, representing nearly 50% of all diabetes cases.

The commission estimated that 3.2 million of these individuals would die in 3 years if not treated, with 1.3 million of these deaths due to cardiovascular disease.

By reducing hemoglobin A1c, blood pressure, and LDL-cholesterol through achieving a diagnosis rate of 50%, ensuring access to essential medicines in at least 70% of patients, and with a support system to sustain reductions in these risk factors over 3 years, up to 800,000 premature deaths could be avoided.
 

People with type 1 diabetes dying; WHO launches initiative

In an accompanying commentary (2020 Nov 12. doi: 10.1016/S0140-6736[20]32378-3), Katie Dain, chief executive officer of the Noncommunicable Diseases (NCD) Alliance, points out that only half of people living with diabetes around the world – and just one in seven in Africa – have reliable access to insulin.

“Lots of people with type 1 diabetes are still dying due to lack of insulin,” Dr. Chan said in an interview. “We need to elevate basic care to intermediate and ensure that basal-bolus insulin and glucose-monitoring tools are available and that patients are trained in self-care. In that way, 80% of type 1 diabetes deaths could be prevented.”

Ms. 3Dain agrees, stressing, “Political rhetoric and commitments have yet to translate into sufficient and sustainable action for people living with diabetes worldwide, and particularly for those in [low- and middle-income countries].”

The Lancet Commission document also emphasizes the importance of support for pregnant women with diabetes and attention to the psychosocial needs of people with diabetes.

And it stresses society-, population-, and community-based strategies for type 2 diabetes prevention including health awareness programs, food policies, and broad use of nonphysician personnel to deliver diabetes prevention efforts.

In tandem with World Diabetes Day, the World Health Organization will announce the development of the WHO Global Diabetes Compact, which will be launched in April 2021.

This will aim to implement the commission’s recommendations through partnerships with governments, care providers, patient advocates, and nongovernmental organizations.

Together, they will “support countries to mobilize resources and accelerate structural transformations, which will enable the scale-up of access to essential diabetes medicines and technologies, inclusion of diagnosis and treatment of diabetes in primary health care and universal health coverage packages, and reduction of major population-level diabetes risk factors such as obesity,” according to another Lancet editorial accompanying the report.

“The evidence-base for improving diabetes prevention and care is strong. The question now for diabetes advocates is how to achieve the comprehensive, systems-level change needed to translate this evidence into action.”

Dr. Chan has reported receiving grants from AstraZeneca, Lilly, Lee Powder, Hua Medicine, and Qualigenics, as well as grants and personal fees from Bayer, Boehringer Ingelheim, Sanofi, Novartis, Merck, and MSD outside the submitted work. She has reported being the chief executive officer (pro bono) of the Asia Diabetes Foundation and a cofounder of GemVCare. She also holds a patent for genetic markers for diabetes and its complications. Ms. Dain has reported no relevant financial relationships.
 

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

"The writing is on the wall” that virtual care is not meeting the needs of people with HIV who struggled with viral suppression even before the COVID-19 pandemic, said Jason Farley, PhD, ANP-BC, AACRN, associate professor of nursing at Johns Hopkins University, Baltimore. So it’s time for HIV care teams, especially clinics in the Ryan White HIV/AIDS Program, to get creative in bringing wraparound services to patients.

That may mean reallocating the workforce so that one person serves as a community health worker. Or it could mean increasing texts and video calls; helping patients find online support groups to address problems with alcohol or drug use; and conducting an overall assessment of patients’ needs as the pandemic continues.

“The virtual patient-centered medical home may be the new normal after COVID-19, and we have to be thinking about how we use this model with patients for whom it works, but supplement this model in patients that it does not,” Farley said at the virtual Association of Nurses in AIDS Care (ANAC) 2020 Annual Meeting. That work “is essential to our being able to facilitate the best patient outcomes possible.”
 

Early data, tiered interventions

Farley referred to an article published in September in the Journal AIDS that confirmed unpublished data mentioned at the International AIDS Conference 2020. The article reported that viral suppression rates among people with HIV who attended San Francisco’s Ward 86 HIV clinic dropped by 31% from pre-COVID levels.

Of the 1766 people who attended the clinic, about 1 in 5 had detectable HIV viral loads at any point in 2019. But that rate was 31% higher after shelter-in-place orders were issued. And although patients participated in telemedicine visits at more or less the same rate before and after the pandemic (31% vs. 30% no-shows), viral suppression rates dropped. The impact was especially acute for homeless individuals.

“This destabilization occurred despite our population attending telemedicine visits at a higher rate than expected, given the 60% drop in ambulatory care visit volume nationwide,” the authors stated in their article. “Telehealth visits, while offering greater patient convenience, may lead to less access to clinic-based social support services essential to achieving viral suppression among vulnerable groups.”

That’s the challenge HIV clinics now face, Farley said at the ANAC meeting.

He suggested a differentiated care approach in which there are four tiers of care, starting with the standard level of outreach, which may include email, electronic health record blasts, and robo-calls to remind people of their appointments and to refill their medications. Those with sustained viral suppression may only need 90-day automatic refills of their medications. Those who are vulnerable to nonadherence may need to be contacted weekly or more often by the clinic. Such contact could be made by a social worker, a community health worker, or through some form of virtual support.

Patients at tier 4, who have labile viral suppression, need far more than that. These are the 15% of patients with HIV who struggled with viral suppression before the pandemic. They are the patients that Farley’s team focuses on at Baltimore’s John G. Bartlett Specialty Clinic for Infectious Disease.

“We’ve completely deconstructed the patient-centered medical home,” he said of the early move to virtual care. He suggested that clinicians assess their services and ask themselves some questions:

• Has someone on the team reached out to every patient and checked in to see what their biggest needs are, medical or not, during the pandemic? Have they assessed the patient’s ability to receive video calls or text messages?
• How have group-support programs that address stigma or the social determinants of health fared in the transition to virtual medicine?
• Are patients who are in recovery being supported in order that they may engage with recovery programs online?
• How well have counseling services done in engaging people in virtual care? Currently, given the overall increase in mental health challenges during the pandemic, one would expect that the use of mental health counseling is increasing. “If they’re stagnant or going down, someone needs to be reflecting on that issue internally in the clinic,” he said.
• Are patients being contacted regarding the effects that isolation is having on their lives? “The things that would normally allow us to self-mitigate and self-manage these conditions, like going to the gym, meeting with friends, religious services – all of those are being cut,” he said.
• Is there an early alert from an in-person pharmacy to trigger outreach via a community health worker for patients who haven’t picked up their medications in a week or more?

Farley pointed to a 2015 model for an enhanced e-health approach to chronic care management that called for e-support from the community and that was enhanced through virtual communities.

These are some of the approaches Farley has taken at his clinic. He leads a team that focuses specifically on patients who struggled with engagement before the pandemic. Through a grant from the US Department of Health & Human Services’ Health Resources and Services Administration – even before the pandemic – that team has been funding community health workers who have multiple contacts with patients online and virtually and are able to offer what he calls “unapologetically enabling” support for patients so that they are able to focus on their health.

He gave the following example. Before the pandemic, a community health worker on the team had been working with a patient who showed up at every scheduled visit and swore that she was taking her medications, although clearly she was not. A community health worker, who was made available through the grant, was able to recognize that the patient’s biggest challenge in her life was providing childcare for her special-needs child. The community health worker worked with the patient for months to find stable childcare for the child, paid 2 months of rent for the patient so that she would not become homeless, and helped her find transitional housing. When the pandemic hit, the community health worker was already texting and conducting video calls with the patient regularly.

For the past 9 months, that patient has had an undetectable viral load, Farley said.

“Nine months during a pandemic,” Farley reiterated, “and the community health worker keeps working with her, keeps meeting with her.”
 

Stigma on stigma

The need for this level of support from the clinic may be even more important for people with HIV who acquire COVID-19, said Orlando Harris, PhD, assistant professor of community health systems at the University of California, San Francisco, (UCSF) School of Nursing. HIV-related stigma is a well-known deterrent to care for people living with the virus. During the presentation, Harris asked Farley about the impact of COVID-19 stigma on people with both HIV and COVID-19.

Farley said that patients at his clinic have told him that they have “ostracized” friends who have tested positive for COVID-19. Harris remembered a person with HIV who participated in one of his trials telling the researchers that despite all his precautions – wearing a mask, staying socially distant – he still acquired COVID-19. There was nothing he could have done, Harris said, other than just not go to the grocery store.

The fear of contracting another disease that is associated with stigma, as well as the need to disclose it, can inflame memories of the trauma of being diagnosed with HIV, Harris said. And with patient-centered medical homes struggling to reconstitute their wraparound services via telehealth, he said he wonders whether clinicians should be doing more.

“I worry about people who have survived being diagnosed with HIV in the ‘80s and the ‘90s before antiretroviral therapy showed up on the scene,” he told Medscape Medical News. “I worry that the folks that survived one pandemic [may] be feeling fearful or living in that fear that this new pandemic might take them out. That’s why I’m stressing the need for us to really consider, as clinicians and also as researchers the support systems, the coping mechanisms, the counseling, or what have you to support those living with HIV and vulnerable to COVID-19.”

During telehealth visits, that can be achieved simply by asking people how they are really doing and what their coping mechanisms are.

For their part, the clinicians at San Francisco’s Ward 86 are not trying to provide that support through telehealth on the same level as they were at the beginning of the pandemic, said Matthew Spinelli, MD, assistant professor of medicine, and Monica Gandhi, MD, associate chief of the Division of HIV, Infectious Diseases and Global Medicine, who are both at UCSF and are coauthors of the study.

They still offer telemedicine appointments to patients who request them, said Spinelli. He said about one-third of his patients still prefer to receive their care virtually. The rest have gone back to face-to-face support.

“The analysis led us to promptly open up care as much as possible to our patients, with the idea that telehealth is not cutting it for vulnerable patients with HIV,” Gandhi told Medscape Medical News via email. “We don’t think it’s right for a population who relies on social support from the clinic.”
 

This article first appeared on Medscape.com.

"The writing is on the wall” that virtual care is not meeting the needs of people with HIV who struggled with viral suppression even before the COVID-19 pandemic, said Jason Farley, PhD, ANP-BC, AACRN, associate professor of nursing at Johns Hopkins University, Baltimore. So it’s time for HIV care teams, especially clinics in the Ryan White HIV/AIDS Program, to get creative in bringing wraparound services to patients.

That may mean reallocating the workforce so that one person serves as a community health worker. Or it could mean increasing texts and video calls; helping patients find online support groups to address problems with alcohol or drug use; and conducting an overall assessment of patients’ needs as the pandemic continues.

“The virtual patient-centered medical home may be the new normal after COVID-19, and we have to be thinking about how we use this model with patients for whom it works, but supplement this model in patients that it does not,” Farley said at the virtual Association of Nurses in AIDS Care (ANAC) 2020 Annual Meeting. That work “is essential to our being able to facilitate the best patient outcomes possible.”
 

Early data, tiered interventions

Farley referred to an article published in September in the Journal AIDS that confirmed unpublished data mentioned at the International AIDS Conference 2020. The article reported that viral suppression rates among people with HIV who attended San Francisco’s Ward 86 HIV clinic dropped by 31% from pre-COVID levels.

Of the 1766 people who attended the clinic, about 1 in 5 had detectable HIV viral loads at any point in 2019. But that rate was 31% higher after shelter-in-place orders were issued. And although patients participated in telemedicine visits at more or less the same rate before and after the pandemic (31% vs. 30% no-shows), viral suppression rates dropped. The impact was especially acute for homeless individuals.

“This destabilization occurred despite our population attending telemedicine visits at a higher rate than expected, given the 60% drop in ambulatory care visit volume nationwide,” the authors stated in their article. “Telehealth visits, while offering greater patient convenience, may lead to less access to clinic-based social support services essential to achieving viral suppression among vulnerable groups.”

That’s the challenge HIV clinics now face, Farley said at the ANAC meeting.

He suggested a differentiated care approach in which there are four tiers of care, starting with the standard level of outreach, which may include email, electronic health record blasts, and robo-calls to remind people of their appointments and to refill their medications. Those with sustained viral suppression may only need 90-day automatic refills of their medications. Those who are vulnerable to nonadherence may need to be contacted weekly or more often by the clinic. Such contact could be made by a social worker, a community health worker, or through some form of virtual support.

Patients at tier 4, who have labile viral suppression, need far more than that. These are the 15% of patients with HIV who struggled with viral suppression before the pandemic. They are the patients that Farley’s team focuses on at Baltimore’s John G. Bartlett Specialty Clinic for Infectious Disease.

“We’ve completely deconstructed the patient-centered medical home,” he said of the early move to virtual care. He suggested that clinicians assess their services and ask themselves some questions:

• Has someone on the team reached out to every patient and checked in to see what their biggest needs are, medical or not, during the pandemic? Have they assessed the patient’s ability to receive video calls or text messages?
• How have group-support programs that address stigma or the social determinants of health fared in the transition to virtual medicine?
• Are patients who are in recovery being supported in order that they may engage with recovery programs online?
• How well have counseling services done in engaging people in virtual care? Currently, given the overall increase in mental health challenges during the pandemic, one would expect that the use of mental health counseling is increasing. “If they’re stagnant or going down, someone needs to be reflecting on that issue internally in the clinic,” he said.
• Are patients being contacted regarding the effects that isolation is having on their lives? “The things that would normally allow us to self-mitigate and self-manage these conditions, like going to the gym, meeting with friends, religious services – all of those are being cut,” he said.
• Is there an early alert from an in-person pharmacy to trigger outreach via a community health worker for patients who haven’t picked up their medications in a week or more?

Farley pointed to a 2015 model for an enhanced e-health approach to chronic care management that called for e-support from the community and that was enhanced through virtual communities.

These are some of the approaches Farley has taken at his clinic. He leads a team that focuses specifically on patients who struggled with engagement before the pandemic. Through a grant from the US Department of Health & Human Services’ Health Resources and Services Administration – even before the pandemic – that team has been funding community health workers who have multiple contacts with patients online and virtually and are able to offer what he calls “unapologetically enabling” support for patients so that they are able to focus on their health.

He gave the following example. Before the pandemic, a community health worker on the team had been working with a patient who showed up at every scheduled visit and swore that she was taking her medications, although clearly she was not. A community health worker, who was made available through the grant, was able to recognize that the patient’s biggest challenge in her life was providing childcare for her special-needs child. The community health worker worked with the patient for months to find stable childcare for the child, paid 2 months of rent for the patient so that she would not become homeless, and helped her find transitional housing. When the pandemic hit, the community health worker was already texting and conducting video calls with the patient regularly.

For the past 9 months, that patient has had an undetectable viral load, Farley said.

“Nine months during a pandemic,” Farley reiterated, “and the community health worker keeps working with her, keeps meeting with her.”
 

Stigma on stigma

The need for this level of support from the clinic may be even more important for people with HIV who acquire COVID-19, said Orlando Harris, PhD, assistant professor of community health systems at the University of California, San Francisco, (UCSF) School of Nursing. HIV-related stigma is a well-known deterrent to care for people living with the virus. During the presentation, Harris asked Farley about the impact of COVID-19 stigma on people with both HIV and COVID-19.

Farley said that patients at his clinic have told him that they have “ostracized” friends who have tested positive for COVID-19. Harris remembered a person with HIV who participated in one of his trials telling the researchers that despite all his precautions – wearing a mask, staying socially distant – he still acquired COVID-19. There was nothing he could have done, Harris said, other than just not go to the grocery store.

The fear of contracting another disease that is associated with stigma, as well as the need to disclose it, can inflame memories of the trauma of being diagnosed with HIV, Harris said. And with patient-centered medical homes struggling to reconstitute their wraparound services via telehealth, he said he wonders whether clinicians should be doing more.

“I worry about people who have survived being diagnosed with HIV in the ‘80s and the ‘90s before antiretroviral therapy showed up on the scene,” he told Medscape Medical News. “I worry that the folks that survived one pandemic [may] be feeling fearful or living in that fear that this new pandemic might take them out. That’s why I’m stressing the need for us to really consider, as clinicians and also as researchers the support systems, the coping mechanisms, the counseling, or what have you to support those living with HIV and vulnerable to COVID-19.”

During telehealth visits, that can be achieved simply by asking people how they are really doing and what their coping mechanisms are.

For their part, the clinicians at San Francisco’s Ward 86 are not trying to provide that support through telehealth on the same level as they were at the beginning of the pandemic, said Matthew Spinelli, MD, assistant professor of medicine, and Monica Gandhi, MD, associate chief of the Division of HIV, Infectious Diseases and Global Medicine, who are both at UCSF and are coauthors of the study.

They still offer telemedicine appointments to patients who request them, said Spinelli. He said about one-third of his patients still prefer to receive their care virtually. The rest have gone back to face-to-face support.

“The analysis led us to promptly open up care as much as possible to our patients, with the idea that telehealth is not cutting it for vulnerable patients with HIV,” Gandhi told Medscape Medical News via email. “We don’t think it’s right for a population who relies on social support from the clinic.”
 

This article first appeared on Medscape.com.

"The writing is on the wall” that virtual care is not meeting the needs of people with HIV who struggled with viral suppression even before the COVID-19 pandemic, said Jason Farley, PhD, ANP-BC, AACRN, associate professor of nursing at Johns Hopkins University, Baltimore. So it’s time for HIV care teams, especially clinics in the Ryan White HIV/AIDS Program, to get creative in bringing wraparound services to patients.

That may mean reallocating the workforce so that one person serves as a community health worker. Or it could mean increasing texts and video calls; helping patients find online support groups to address problems with alcohol or drug use; and conducting an overall assessment of patients’ needs as the pandemic continues.

“The virtual patient-centered medical home may be the new normal after COVID-19, and we have to be thinking about how we use this model with patients for whom it works, but supplement this model in patients that it does not,” Farley said at the virtual Association of Nurses in AIDS Care (ANAC) 2020 Annual Meeting. That work “is essential to our being able to facilitate the best patient outcomes possible.”
 

Early data, tiered interventions

Farley referred to an article published in September in the Journal AIDS that confirmed unpublished data mentioned at the International AIDS Conference 2020. The article reported that viral suppression rates among people with HIV who attended San Francisco’s Ward 86 HIV clinic dropped by 31% from pre-COVID levels.

Of the 1766 people who attended the clinic, about 1 in 5 had detectable HIV viral loads at any point in 2019. But that rate was 31% higher after shelter-in-place orders were issued. And although patients participated in telemedicine visits at more or less the same rate before and after the pandemic (31% vs. 30% no-shows), viral suppression rates dropped. The impact was especially acute for homeless individuals.

“This destabilization occurred despite our population attending telemedicine visits at a higher rate than expected, given the 60% drop in ambulatory care visit volume nationwide,” the authors stated in their article. “Telehealth visits, while offering greater patient convenience, may lead to less access to clinic-based social support services essential to achieving viral suppression among vulnerable groups.”

That’s the challenge HIV clinics now face, Farley said at the ANAC meeting.

He suggested a differentiated care approach in which there are four tiers of care, starting with the standard level of outreach, which may include email, electronic health record blasts, and robo-calls to remind people of their appointments and to refill their medications. Those with sustained viral suppression may only need 90-day automatic refills of their medications. Those who are vulnerable to nonadherence may need to be contacted weekly or more often by the clinic. Such contact could be made by a social worker, a community health worker, or through some form of virtual support.

Patients at tier 4, who have labile viral suppression, need far more than that. These are the 15% of patients with HIV who struggled with viral suppression before the pandemic. They are the patients that Farley’s team focuses on at Baltimore’s John G. Bartlett Specialty Clinic for Infectious Disease.

“We’ve completely deconstructed the patient-centered medical home,” he said of the early move to virtual care. He suggested that clinicians assess their services and ask themselves some questions:

• Has someone on the team reached out to every patient and checked in to see what their biggest needs are, medical or not, during the pandemic? Have they assessed the patient’s ability to receive video calls or text messages?
• How have group-support programs that address stigma or the social determinants of health fared in the transition to virtual medicine?
• Are patients who are in recovery being supported in order that they may engage with recovery programs online?
• How well have counseling services done in engaging people in virtual care? Currently, given the overall increase in mental health challenges during the pandemic, one would expect that the use of mental health counseling is increasing. “If they’re stagnant or going down, someone needs to be reflecting on that issue internally in the clinic,” he said.
• Are patients being contacted regarding the effects that isolation is having on their lives? “The things that would normally allow us to self-mitigate and self-manage these conditions, like going to the gym, meeting with friends, religious services – all of those are being cut,” he said.
• Is there an early alert from an in-person pharmacy to trigger outreach via a community health worker for patients who haven’t picked up their medications in a week or more?

Farley pointed to a 2015 model for an enhanced e-health approach to chronic care management that called for e-support from the community and that was enhanced through virtual communities.

These are some of the approaches Farley has taken at his clinic. He leads a team that focuses specifically on patients who struggled with engagement before the pandemic. Through a grant from the US Department of Health & Human Services’ Health Resources and Services Administration – even before the pandemic – that team has been funding community health workers who have multiple contacts with patients online and virtually and are able to offer what he calls “unapologetically enabling” support for patients so that they are able to focus on their health.

He gave the following example. Before the pandemic, a community health worker on the team had been working with a patient who showed up at every scheduled visit and swore that she was taking her medications, although clearly she was not. A community health worker, who was made available through the grant, was able to recognize that the patient’s biggest challenge in her life was providing childcare for her special-needs child. The community health worker worked with the patient for months to find stable childcare for the child, paid 2 months of rent for the patient so that she would not become homeless, and helped her find transitional housing. When the pandemic hit, the community health worker was already texting and conducting video calls with the patient regularly.

For the past 9 months, that patient has had an undetectable viral load, Farley said.

“Nine months during a pandemic,” Farley reiterated, “and the community health worker keeps working with her, keeps meeting with her.”
 

Stigma on stigma

The need for this level of support from the clinic may be even more important for people with HIV who acquire COVID-19, said Orlando Harris, PhD, assistant professor of community health systems at the University of California, San Francisco, (UCSF) School of Nursing. HIV-related stigma is a well-known deterrent to care for people living with the virus. During the presentation, Harris asked Farley about the impact of COVID-19 stigma on people with both HIV and COVID-19.

Farley said that patients at his clinic have told him that they have “ostracized” friends who have tested positive for COVID-19. Harris remembered a person with HIV who participated in one of his trials telling the researchers that despite all his precautions – wearing a mask, staying socially distant – he still acquired COVID-19. There was nothing he could have done, Harris said, other than just not go to the grocery store.

The fear of contracting another disease that is associated with stigma, as well as the need to disclose it, can inflame memories of the trauma of being diagnosed with HIV, Harris said. And with patient-centered medical homes struggling to reconstitute their wraparound services via telehealth, he said he wonders whether clinicians should be doing more.

“I worry about people who have survived being diagnosed with HIV in the ‘80s and the ‘90s before antiretroviral therapy showed up on the scene,” he told Medscape Medical News. “I worry that the folks that survived one pandemic [may] be feeling fearful or living in that fear that this new pandemic might take them out. That’s why I’m stressing the need for us to really consider, as clinicians and also as researchers the support systems, the coping mechanisms, the counseling, or what have you to support those living with HIV and vulnerable to COVID-19.”

During telehealth visits, that can be achieved simply by asking people how they are really doing and what their coping mechanisms are.

For their part, the clinicians at San Francisco’s Ward 86 are not trying to provide that support through telehealth on the same level as they were at the beginning of the pandemic, said Matthew Spinelli, MD, assistant professor of medicine, and Monica Gandhi, MD, associate chief of the Division of HIV, Infectious Diseases and Global Medicine, who are both at UCSF and are coauthors of the study.

They still offer telemedicine appointments to patients who request them, said Spinelli. He said about one-third of his patients still prefer to receive their care virtually. The rest have gone back to face-to-face support.

“The analysis led us to promptly open up care as much as possible to our patients, with the idea that telehealth is not cutting it for vulnerable patients with HIV,” Gandhi told Medscape Medical News via email. “We don’t think it’s right for a population who relies on social support from the clinic.”
 

This article first appeared on Medscape.com.

A new guideline from the Kidney Disease: Improving Global Outcomes group addressing issues around diabetes management in patients with chronic kidney disease (CKD) has just been published in synopsis form in Annals of Internal Medicine.

The full guideline, including 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD, was published last month in Kidney International and on the KDIGO website.

More than 40% of people with diabetes develop CKD, and a significant number develop kidney failure requiring dialysis or transplant. This is the first guidance from KDIGO to address the comorbidity.

The new synopsis is aimed at primary care and nonnephrology specialist clinicians who manage patients with diabetes and CKD, in addition to nephrologists, first author Sankar D. Navaneethan, MD, said in an interview.

“Most of these patients are in the hands of primary care, endocrinology, and cardiology. We want to emphasize when they see patients with different severities of kidney disease [is] what are some of the things they have to be cognizant of,” said Dr. Navaneethan, professor of medicine and director of clinical research in the section of nephrology at Baylor College of Medicine, Houston.

The synopsis summarizes key recommendations from the larger guidance regarding comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, glucose-lowering therapies, and educational/integrated care approaches.

It does not depart from prior diabetes guidelines, but it does provide advice for specific situations relevant to CKD, such as the limitations of hemoglobin A1c when estimated glomerular filtration rate (eGFR) drops below 30 mL/min per 1.73m², and dietary protein consumption. It is based on published evidence up until February 2020.

For the nephrologist audience in particular, Dr. Navaneethan said, “we wanted to highlight team-based care, interacting with other specialists and working with them.”

“We [nephrologists] are more used to team-based care in dialysis patients. ... So we wanted to highlight that self-management programs and team-based care are important for empowering patients.”

“As nephrologists, we might not be comfortable starting patients on an SGLT2 [sodium-glucose cotransporter 2] inhibitor. We may need to reach out to our endocrinology or primary care colleagues and learn from them,” he explained.
 

RAS inhibitor use, smoking cessation, glycemic targets

Under “comprehensive care,” the guideline panel recommends treatment with an ACE inhibitor or an angiotensin II receptor blocker – renin-angiotensin system (RAS) blockade – for patients with diabetes, hypertension, and albuminuria (albumin-creatinine ratio >30 mg/g).

These medications should be titrated to the highest approved tolerated dose, with close monitoring of serum potassium and serum creatinine levels within 2-4 weeks of initiation or change in dose.

The document guides clinicians on that monitoring, as well as on RAS blockade use in patient subgroups, use of alternative agents, and mitigation of adverse effects.

Patients with diabetes and CKD who use tobacco should be advised to quit.

The group recommended A1c to monitor glycemic control in patients with diabetes and CKD not receiving dialysis.

However, when eGFR is below 30 mL/min per 1.73m2, A1c levels tend to be lower because of shortened erythrocyte lifespan, which interpretation should take into account. Continuous glucose monitoring can be used as an alternative because it is not affected by CKD.

Glycemic targets should be individualized depending on hypoglycemia risk, ranging from 6.5% to 8.0% for A1c or time in range of 70-180 mg/dL for continuous glucose monitoring readings.
 

SGLT2 inhibitors, metformin, and GLP-1 agonists

The panel also recommends treatment with both metformin and an SGLT2 inhibitor for patients with type 2 diabetes, CKD, and an eGFR ≥30 mL/min per 1.73m2.

For those who do not achieve glycemic targets or who cannot take those medications, a long-acting glucagonlike peptide–1 receptor agonist can be used instead.

Clinical trial data are summarized for the SGLT2 inhibitor canagliflozin supporting its use in patients with CKD specifically, along with mitigation of adverse events. Last year, the Food and Drug Administration approved this agent to slow the progression of diabetic nephropathy based on the CREDENCE study.

Results from the DAPA-CKD trial showing CKD reduction with another SGLT2 inhibitor, dapagliflozin, were not available at the time the new document was written, nor was the recent study showing diabetic CKD benefit for the novel mineralocorticoid receptor antagonist finerenone, Dr. Navaneethan noted.

The panel determined that there is insufficient evidence for adding other glucose-lowering agents to insulin in patients with type 1 diabetes and CKD.
 

Lifestyle interventions: Dietary protein, sodium, and physical activity

Most of the dietary guidance for patients with diabetes and CKD is the same as for the general population, including a recommendation to eat a diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts, and lower in processed meats, refined carbohydrates, and sweetened beverages.

However, the guideline details two key areas that differ, one with regard to protein intake and the other on sodium.

Although lower protein intake had been advised in the past for patients with CKD, clinical trial evidence has not shown protein restriction to reduce glomerular hyperfiltration or slow kidney disease progression.

Therefore, the same level recommended for the general population – 0.8 g/kg per day – is also advised for those with diabetes and CKD who are not on dialysis.

Those who are on dialysis can increase daily protein intake to 1.0-1.2 g/kg per day to offset catabolism and negative nitrogen imbalance.

Because kidney function decline is associated with sodium retention that can raise cardiovascular risk, sodium should be limited to less than 2 g/day (or less than 90 mmol or 5 g of sodium chloride per day).

The panel also recommended moderate-intensity physical activity for at least 150 minutes per week or to tolerance.

“We wanted to emphasize how important lifestyle is. It’s the foundation you want to build on. You can take medications without all these other things – exercise, diet, weight loss – but they won’t be nearly as effective,” Dr. Navaneethan commented.
 

Self-management education, team-based care

The final section of the synopsis advises that people with diabetes and CKD receive structured self-management educational programs, and that “policy makers and institutional decision-makers implement team-based, integrated care focused on risk evaluation and patient empowerment to provide comprehensive care in patients with diabetes and CKD.”

Despite limited data for those measures specifically in patients with diabetes and CKD, “the working group believed that well-informed patients would choose self-management as the cornerstone of any chronic care model; therefore, a high value was placed on the potential benefits of self-management education programs in persons with diabetes and CKD.”

And regarding team-based care, “despite a paucity of direct evidence, the working group judged that multidisciplinary integrated care for patients with diabetes and CKD would represent a good investment.”

The guidelines will likely be updated in the next 1-2 years, Dr. Navaneethan said in an interview.

Dr. Navaneethan has reported receiving consultancy fees from Bayer, Boehringer Ingelheim, Reata, and Tricida, and research support from Keryx.

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

A new guideline from the Kidney Disease: Improving Global Outcomes group addressing issues around diabetes management in patients with chronic kidney disease (CKD) has just been published in synopsis form in Annals of Internal Medicine.

The full guideline, including 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD, was published last month in Kidney International and on the KDIGO website.

More than 40% of people with diabetes develop CKD, and a significant number develop kidney failure requiring dialysis or transplant. This is the first guidance from KDIGO to address the comorbidity.

The new synopsis is aimed at primary care and nonnephrology specialist clinicians who manage patients with diabetes and CKD, in addition to nephrologists, first author Sankar D. Navaneethan, MD, said in an interview.

“Most of these patients are in the hands of primary care, endocrinology, and cardiology. We want to emphasize when they see patients with different severities of kidney disease [is] what are some of the things they have to be cognizant of,” said Dr. Navaneethan, professor of medicine and director of clinical research in the section of nephrology at Baylor College of Medicine, Houston.

The synopsis summarizes key recommendations from the larger guidance regarding comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, glucose-lowering therapies, and educational/integrated care approaches.

It does not depart from prior diabetes guidelines, but it does provide advice for specific situations relevant to CKD, such as the limitations of hemoglobin A1c when estimated glomerular filtration rate (eGFR) drops below 30 mL/min per 1.73m², and dietary protein consumption. It is based on published evidence up until February 2020.

For the nephrologist audience in particular, Dr. Navaneethan said, “we wanted to highlight team-based care, interacting with other specialists and working with them.”

“We [nephrologists] are more used to team-based care in dialysis patients. ... So we wanted to highlight that self-management programs and team-based care are important for empowering patients.”

“As nephrologists, we might not be comfortable starting patients on an SGLT2 [sodium-glucose cotransporter 2] inhibitor. We may need to reach out to our endocrinology or primary care colleagues and learn from them,” he explained.
 

RAS inhibitor use, smoking cessation, glycemic targets

Under “comprehensive care,” the guideline panel recommends treatment with an ACE inhibitor or an angiotensin II receptor blocker – renin-angiotensin system (RAS) blockade – for patients with diabetes, hypertension, and albuminuria (albumin-creatinine ratio >30 mg/g).

These medications should be titrated to the highest approved tolerated dose, with close monitoring of serum potassium and serum creatinine levels within 2-4 weeks of initiation or change in dose.

The document guides clinicians on that monitoring, as well as on RAS blockade use in patient subgroups, use of alternative agents, and mitigation of adverse effects.

Patients with diabetes and CKD who use tobacco should be advised to quit.

The group recommended A1c to monitor glycemic control in patients with diabetes and CKD not receiving dialysis.

However, when eGFR is below 30 mL/min per 1.73m2, A1c levels tend to be lower because of shortened erythrocyte lifespan, which interpretation should take into account. Continuous glucose monitoring can be used as an alternative because it is not affected by CKD.

Glycemic targets should be individualized depending on hypoglycemia risk, ranging from 6.5% to 8.0% for A1c or time in range of 70-180 mg/dL for continuous glucose monitoring readings.
 

SGLT2 inhibitors, metformin, and GLP-1 agonists

The panel also recommends treatment with both metformin and an SGLT2 inhibitor for patients with type 2 diabetes, CKD, and an eGFR ≥30 mL/min per 1.73m2.

For those who do not achieve glycemic targets or who cannot take those medications, a long-acting glucagonlike peptide–1 receptor agonist can be used instead.

Clinical trial data are summarized for the SGLT2 inhibitor canagliflozin supporting its use in patients with CKD specifically, along with mitigation of adverse events. Last year, the Food and Drug Administration approved this agent to slow the progression of diabetic nephropathy based on the CREDENCE study.

Results from the DAPA-CKD trial showing CKD reduction with another SGLT2 inhibitor, dapagliflozin, were not available at the time the new document was written, nor was the recent study showing diabetic CKD benefit for the novel mineralocorticoid receptor antagonist finerenone, Dr. Navaneethan noted.

The panel determined that there is insufficient evidence for adding other glucose-lowering agents to insulin in patients with type 1 diabetes and CKD.
 

Lifestyle interventions: Dietary protein, sodium, and physical activity

Most of the dietary guidance for patients with diabetes and CKD is the same as for the general population, including a recommendation to eat a diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts, and lower in processed meats, refined carbohydrates, and sweetened beverages.

However, the guideline details two key areas that differ, one with regard to protein intake and the other on sodium.

Although lower protein intake had been advised in the past for patients with CKD, clinical trial evidence has not shown protein restriction to reduce glomerular hyperfiltration or slow kidney disease progression.

Therefore, the same level recommended for the general population – 0.8 g/kg per day – is also advised for those with diabetes and CKD who are not on dialysis.

Those who are on dialysis can increase daily protein intake to 1.0-1.2 g/kg per day to offset catabolism and negative nitrogen imbalance.

Because kidney function decline is associated with sodium retention that can raise cardiovascular risk, sodium should be limited to less than 2 g/day (or less than 90 mmol or 5 g of sodium chloride per day).

The panel also recommended moderate-intensity physical activity for at least 150 minutes per week or to tolerance.

“We wanted to emphasize how important lifestyle is. It’s the foundation you want to build on. You can take medications without all these other things – exercise, diet, weight loss – but they won’t be nearly as effective,” Dr. Navaneethan commented.
 

Self-management education, team-based care

The final section of the synopsis advises that people with diabetes and CKD receive structured self-management educational programs, and that “policy makers and institutional decision-makers implement team-based, integrated care focused on risk evaluation and patient empowerment to provide comprehensive care in patients with diabetes and CKD.”

Despite limited data for those measures specifically in patients with diabetes and CKD, “the working group believed that well-informed patients would choose self-management as the cornerstone of any chronic care model; therefore, a high value was placed on the potential benefits of self-management education programs in persons with diabetes and CKD.”

And regarding team-based care, “despite a paucity of direct evidence, the working group judged that multidisciplinary integrated care for patients with diabetes and CKD would represent a good investment.”

The guidelines will likely be updated in the next 1-2 years, Dr. Navaneethan said in an interview.

Dr. Navaneethan has reported receiving consultancy fees from Bayer, Boehringer Ingelheim, Reata, and Tricida, and research support from Keryx.

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

A new guideline from the Kidney Disease: Improving Global Outcomes group addressing issues around diabetes management in patients with chronic kidney disease (CKD) has just been published in synopsis form in Annals of Internal Medicine.

The full guideline, including 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD, was published last month in Kidney International and on the KDIGO website.

More than 40% of people with diabetes develop CKD, and a significant number develop kidney failure requiring dialysis or transplant. This is the first guidance from KDIGO to address the comorbidity.

The new synopsis is aimed at primary care and nonnephrology specialist clinicians who manage patients with diabetes and CKD, in addition to nephrologists, first author Sankar D. Navaneethan, MD, said in an interview.

“Most of these patients are in the hands of primary care, endocrinology, and cardiology. We want to emphasize when they see patients with different severities of kidney disease [is] what are some of the things they have to be cognizant of,” said Dr. Navaneethan, professor of medicine and director of clinical research in the section of nephrology at Baylor College of Medicine, Houston.

The synopsis summarizes key recommendations from the larger guidance regarding comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, glucose-lowering therapies, and educational/integrated care approaches.

It does not depart from prior diabetes guidelines, but it does provide advice for specific situations relevant to CKD, such as the limitations of hemoglobin A1c when estimated glomerular filtration rate (eGFR) drops below 30 mL/min per 1.73m², and dietary protein consumption. It is based on published evidence up until February 2020.

For the nephrologist audience in particular, Dr. Navaneethan said, “we wanted to highlight team-based care, interacting with other specialists and working with them.”

“We [nephrologists] are more used to team-based care in dialysis patients. ... So we wanted to highlight that self-management programs and team-based care are important for empowering patients.”

“As nephrologists, we might not be comfortable starting patients on an SGLT2 [sodium-glucose cotransporter 2] inhibitor. We may need to reach out to our endocrinology or primary care colleagues and learn from them,” he explained.
 

RAS inhibitor use, smoking cessation, glycemic targets

Under “comprehensive care,” the guideline panel recommends treatment with an ACE inhibitor or an angiotensin II receptor blocker – renin-angiotensin system (RAS) blockade – for patients with diabetes, hypertension, and albuminuria (albumin-creatinine ratio >30 mg/g).

These medications should be titrated to the highest approved tolerated dose, with close monitoring of serum potassium and serum creatinine levels within 2-4 weeks of initiation or change in dose.

The document guides clinicians on that monitoring, as well as on RAS blockade use in patient subgroups, use of alternative agents, and mitigation of adverse effects.

Patients with diabetes and CKD who use tobacco should be advised to quit.

The group recommended A1c to monitor glycemic control in patients with diabetes and CKD not receiving dialysis.

However, when eGFR is below 30 mL/min per 1.73m2, A1c levels tend to be lower because of shortened erythrocyte lifespan, which interpretation should take into account. Continuous glucose monitoring can be used as an alternative because it is not affected by CKD.

Glycemic targets should be individualized depending on hypoglycemia risk, ranging from 6.5% to 8.0% for A1c or time in range of 70-180 mg/dL for continuous glucose monitoring readings.
 

SGLT2 inhibitors, metformin, and GLP-1 agonists

The panel also recommends treatment with both metformin and an SGLT2 inhibitor for patients with type 2 diabetes, CKD, and an eGFR ≥30 mL/min per 1.73m2.

For those who do not achieve glycemic targets or who cannot take those medications, a long-acting glucagonlike peptide–1 receptor agonist can be used instead.

Clinical trial data are summarized for the SGLT2 inhibitor canagliflozin supporting its use in patients with CKD specifically, along with mitigation of adverse events. Last year, the Food and Drug Administration approved this agent to slow the progression of diabetic nephropathy based on the CREDENCE study.

Results from the DAPA-CKD trial showing CKD reduction with another SGLT2 inhibitor, dapagliflozin, were not available at the time the new document was written, nor was the recent study showing diabetic CKD benefit for the novel mineralocorticoid receptor antagonist finerenone, Dr. Navaneethan noted.

The panel determined that there is insufficient evidence for adding other glucose-lowering agents to insulin in patients with type 1 diabetes and CKD.
 

Lifestyle interventions: Dietary protein, sodium, and physical activity

Most of the dietary guidance for patients with diabetes and CKD is the same as for the general population, including a recommendation to eat a diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts, and lower in processed meats, refined carbohydrates, and sweetened beverages.

However, the guideline details two key areas that differ, one with regard to protein intake and the other on sodium.

Although lower protein intake had been advised in the past for patients with CKD, clinical trial evidence has not shown protein restriction to reduce glomerular hyperfiltration or slow kidney disease progression.

Therefore, the same level recommended for the general population – 0.8 g/kg per day – is also advised for those with diabetes and CKD who are not on dialysis.

Those who are on dialysis can increase daily protein intake to 1.0-1.2 g/kg per day to offset catabolism and negative nitrogen imbalance.

Because kidney function decline is associated with sodium retention that can raise cardiovascular risk, sodium should be limited to less than 2 g/day (or less than 90 mmol or 5 g of sodium chloride per day).

The panel also recommended moderate-intensity physical activity for at least 150 minutes per week or to tolerance.

“We wanted to emphasize how important lifestyle is. It’s the foundation you want to build on. You can take medications without all these other things – exercise, diet, weight loss – but they won’t be nearly as effective,” Dr. Navaneethan commented.
 

Self-management education, team-based care

The final section of the synopsis advises that people with diabetes and CKD receive structured self-management educational programs, and that “policy makers and institutional decision-makers implement team-based, integrated care focused on risk evaluation and patient empowerment to provide comprehensive care in patients with diabetes and CKD.”

Despite limited data for those measures specifically in patients with diabetes and CKD, “the working group believed that well-informed patients would choose self-management as the cornerstone of any chronic care model; therefore, a high value was placed on the potential benefits of self-management education programs in persons with diabetes and CKD.”

And regarding team-based care, “despite a paucity of direct evidence, the working group judged that multidisciplinary integrated care for patients with diabetes and CKD would represent a good investment.”

The guidelines will likely be updated in the next 1-2 years, Dr. Navaneethan said in an interview.

Dr. Navaneethan has reported receiving consultancy fees from Bayer, Boehringer Ingelheim, Reata, and Tricida, and research support from Keryx.

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

Cardiovascular disease risk is elevated among transgender individuals seeking gender-affirming hormone therapy, according to a retrospective study in 427 patients.

nktwentythree/Getty Images

The transgender population often experiences socioeconomic and health disparities, including reduced access to care, Kara J. Denby, MD, said in an interview.

Previous research suggests that the use of gender-affirming hormone therapy (GAHT) may place transgender persons at increased cardiovascular risk, she said.

To identify the potential risk for transgender individuals, the researchers identified baseline cardiovascular risk in patients who had not yet undergone GAHT. Study participants were enrolled in a multidisciplinary transgender program, and the researchers collected data on demographics, medical history, vitals, medications, and laboratory results. The average age of the participants was 26 years, 172 identified as men, 236 as women, and 20 as nonbinary.

Overall, 55% of the participants had a chronic medical condition at baseline. Of these, 74 patients had hypertension, 41 had hyperlipidemia, 2 had a history of stroke, 7 had coronary artery disease, and 4 had chronic obstructive pulmonary disease.

For all patients who did not have documented atherosclerotic cardiovascular disease, their American College of Cardiology/American Heart Association ASCVD and QRISK3 risk scores were calculated. “The incidence of undiagnosed hypertension and hyperlipidemia was 6.8% and 11.3% respectively, and of these cases, only 64% and 24% were on appropriate therapies,” noted Dr. Denby of the Cleveland (Ohio) Clinic.

She reported the results Nov. 13 in a presentation at the at the virtual American Heart Association scientific sessions.

The findings were limited by the observational nature of the study.

However, the results suggest that transgender patients “appear to be at higher risk than their age-matched historical cohorts regardless of gender,” said Dr. Denby. More research is needed, but cardiovascular disease–prevention efforts may be inadequate in the transgender population given the elevated risk observed in this study, she concluded.
 

Growing transgender population is medically underserved

The transgender population is growing in the United States and internationally, said Dr. Denby. “This group has a history of being marginalized as a result of their transgender status with socioeconomic and health repercussions,” she said. “It is well known that transgender patients are less likely to have access to health care or utilize health care for a variety of reasons, including stigma and fear of mistreatment. This often leads transgender individuals to present to care late in disease processes which makes their disease harder to treat and often leads to emergent medical conditions,” she added.

“Transgender men and women are at high risk for cardiovascular disease and often aren’t screened at recommended intervals because of decreased health care use compared to their cisgender counterparts,” she said. “This may lead to untreated diseases that make them even more likely to suffer poor health outcomes.”

The current study is important because there are “almost no prior data regarding the cardiovascular health status of this population prior to gender-affirming care,” Dr. Denby emphasized. “There are data that gay, lesbian, and bisexual individuals are at higher risk for poor cardiovascular outcomes, but the same data are lacking in the transgender group,” she said.

“As transgender individuals have frequent physician visits while on hormonal therapy, this seems like the opportune time to screen for cardiovascular risk factors and treat previously undiagnosed diseases that can lead to poor health outcomes in the future,” Dr. Denby explained. “If we are able to intervene at an earlier age, perhaps we can help prevent poor health outcomes down the road,” she said.
 

Additional research can inform practice

Dr. Denby said she was not surprised by the findings. “This is a very high-risk population that often doesn’t follow closely in the health care system,” she said. “These data are very important in thinking holistically about transgender patients.” Clinicians can “use the opportunities we have when they present for gender-affirming care to optimize their overall health status, promote long-term health, and reduce the risks associated with hormonal therapy and gender-affirming surgeries,” she noted. “We hope to use this information to change our practice at the Cleveland Clinic and nationally as well. Transgender patients should be screened and aggressively treated for cardiovascular disease and risk factors,” she said.

Key barriers to overcome include determining the best way to reach out to transgender individuals and then making them feel comfortable in the clinical setting, Dr. Denby said. “This means that we must set up clinics that are approachable and safe for all comers. The lack of laws in many states that protect this vulnerable population also contributes to lack of access to care,” she added. 

“We hope to continue research in this arena about how to effectively screen and treat transgender patients as they present to care, not only in the transgender clinic, but also to primary care providers (ob.gyn., internal medicine, family medicine, pediatrics) who also care for this population” since no specific guidelines currently exist to direct the screening for cardiovascular patients in particular, she said.
 

Findings offer foundation for LGBTQ cardiovascular studies

“This [study] provides us with a good rationale for why we should be considering cardiovascular health in transgender adults,” Billy A. Caceres, PhD, RN, of Columbia University School of Nursing, New York, said in an interview. “It is largely descriptive, but I think that that’s a good step in terms of at least understanding the magnitude of this problem. In addition, I think that what this abstract might do is help lead to future research that examines potentially the associations between not only gender-affirming hormone therapies but other potential social determinants like discrimination or poverty on the cardiovascular health of transgender people,” he noted.

Dr. Caceres served as chair of the writing group for the recent American Heart Association Scientific Statement: LGBTQ Heart Health published in Circulation. He had no financial conflicts to disclose.

The study received no outside funding. Dr. Denby had no financial conflicts to disclose.

SOURCE: Denby KJ et al. AHA 2020, Presentation P2274.

Cardiovascular disease risk is elevated among transgender individuals seeking gender-affirming hormone therapy, according to a retrospective study in 427 patients.

nktwentythree/Getty Images

The transgender population often experiences socioeconomic and health disparities, including reduced access to care, Kara J. Denby, MD, said in an interview.

Previous research suggests that the use of gender-affirming hormone therapy (GAHT) may place transgender persons at increased cardiovascular risk, she said.

To identify the potential risk for transgender individuals, the researchers identified baseline cardiovascular risk in patients who had not yet undergone GAHT. Study participants were enrolled in a multidisciplinary transgender program, and the researchers collected data on demographics, medical history, vitals, medications, and laboratory results. The average age of the participants was 26 years, 172 identified as men, 236 as women, and 20 as nonbinary.

Overall, 55% of the participants had a chronic medical condition at baseline. Of these, 74 patients had hypertension, 41 had hyperlipidemia, 2 had a history of stroke, 7 had coronary artery disease, and 4 had chronic obstructive pulmonary disease.

For all patients who did not have documented atherosclerotic cardiovascular disease, their American College of Cardiology/American Heart Association ASCVD and QRISK3 risk scores were calculated. “The incidence of undiagnosed hypertension and hyperlipidemia was 6.8% and 11.3% respectively, and of these cases, only 64% and 24% were on appropriate therapies,” noted Dr. Denby of the Cleveland (Ohio) Clinic.

She reported the results Nov. 13 in a presentation at the at the virtual American Heart Association scientific sessions.

The findings were limited by the observational nature of the study.

However, the results suggest that transgender patients “appear to be at higher risk than their age-matched historical cohorts regardless of gender,” said Dr. Denby. More research is needed, but cardiovascular disease–prevention efforts may be inadequate in the transgender population given the elevated risk observed in this study, she concluded.
 

Growing transgender population is medically underserved

The transgender population is growing in the United States and internationally, said Dr. Denby. “This group has a history of being marginalized as a result of their transgender status with socioeconomic and health repercussions,” she said. “It is well known that transgender patients are less likely to have access to health care or utilize health care for a variety of reasons, including stigma and fear of mistreatment. This often leads transgender individuals to present to care late in disease processes which makes their disease harder to treat and often leads to emergent medical conditions,” she added.

“Transgender men and women are at high risk for cardiovascular disease and often aren’t screened at recommended intervals because of decreased health care use compared to their cisgender counterparts,” she said. “This may lead to untreated diseases that make them even more likely to suffer poor health outcomes.”

The current study is important because there are “almost no prior data regarding the cardiovascular health status of this population prior to gender-affirming care,” Dr. Denby emphasized. “There are data that gay, lesbian, and bisexual individuals are at higher risk for poor cardiovascular outcomes, but the same data are lacking in the transgender group,” she said.

“As transgender individuals have frequent physician visits while on hormonal therapy, this seems like the opportune time to screen for cardiovascular risk factors and treat previously undiagnosed diseases that can lead to poor health outcomes in the future,” Dr. Denby explained. “If we are able to intervene at an earlier age, perhaps we can help prevent poor health outcomes down the road,” she said.
 

Additional research can inform practice

Dr. Denby said she was not surprised by the findings. “This is a very high-risk population that often doesn’t follow closely in the health care system,” she said. “These data are very important in thinking holistically about transgender patients.” Clinicians can “use the opportunities we have when they present for gender-affirming care to optimize their overall health status, promote long-term health, and reduce the risks associated with hormonal therapy and gender-affirming surgeries,” she noted. “We hope to use this information to change our practice at the Cleveland Clinic and nationally as well. Transgender patients should be screened and aggressively treated for cardiovascular disease and risk factors,” she said.

Key barriers to overcome include determining the best way to reach out to transgender individuals and then making them feel comfortable in the clinical setting, Dr. Denby said. “This means that we must set up clinics that are approachable and safe for all comers. The lack of laws in many states that protect this vulnerable population also contributes to lack of access to care,” she added. 

“We hope to continue research in this arena about how to effectively screen and treat transgender patients as they present to care, not only in the transgender clinic, but also to primary care providers (ob.gyn., internal medicine, family medicine, pediatrics) who also care for this population” since no specific guidelines currently exist to direct the screening for cardiovascular patients in particular, she said.
 

Findings offer foundation for LGBTQ cardiovascular studies

“This [study] provides us with a good rationale for why we should be considering cardiovascular health in transgender adults,” Billy A. Caceres, PhD, RN, of Columbia University School of Nursing, New York, said in an interview. “It is largely descriptive, but I think that that’s a good step in terms of at least understanding the magnitude of this problem. In addition, I think that what this abstract might do is help lead to future research that examines potentially the associations between not only gender-affirming hormone therapies but other potential social determinants like discrimination or poverty on the cardiovascular health of transgender people,” he noted.

Dr. Caceres served as chair of the writing group for the recent American Heart Association Scientific Statement: LGBTQ Heart Health published in Circulation. He had no financial conflicts to disclose.

The study received no outside funding. Dr. Denby had no financial conflicts to disclose.

SOURCE: Denby KJ et al. AHA 2020, Presentation P2274.

Cardiovascular disease risk is elevated among transgender individuals seeking gender-affirming hormone therapy, according to a retrospective study in 427 patients.

nktwentythree/Getty Images

The transgender population often experiences socioeconomic and health disparities, including reduced access to care, Kara J. Denby, MD, said in an interview.

Previous research suggests that the use of gender-affirming hormone therapy (GAHT) may place transgender persons at increased cardiovascular risk, she said.

To identify the potential risk for transgender individuals, the researchers identified baseline cardiovascular risk in patients who had not yet undergone GAHT. Study participants were enrolled in a multidisciplinary transgender program, and the researchers collected data on demographics, medical history, vitals, medications, and laboratory results. The average age of the participants was 26 years, 172 identified as men, 236 as women, and 20 as nonbinary.

Overall, 55% of the participants had a chronic medical condition at baseline. Of these, 74 patients had hypertension, 41 had hyperlipidemia, 2 had a history of stroke, 7 had coronary artery disease, and 4 had chronic obstructive pulmonary disease.

For all patients who did not have documented atherosclerotic cardiovascular disease, their American College of Cardiology/American Heart Association ASCVD and QRISK3 risk scores were calculated. “The incidence of undiagnosed hypertension and hyperlipidemia was 6.8% and 11.3% respectively, and of these cases, only 64% and 24% were on appropriate therapies,” noted Dr. Denby of the Cleveland (Ohio) Clinic.

She reported the results Nov. 13 in a presentation at the at the virtual American Heart Association scientific sessions.

The findings were limited by the observational nature of the study.

However, the results suggest that transgender patients “appear to be at higher risk than their age-matched historical cohorts regardless of gender,” said Dr. Denby. More research is needed, but cardiovascular disease–prevention efforts may be inadequate in the transgender population given the elevated risk observed in this study, she concluded.
 

Growing transgender population is medically underserved

The transgender population is growing in the United States and internationally, said Dr. Denby. “This group has a history of being marginalized as a result of their transgender status with socioeconomic and health repercussions,” she said. “It is well known that transgender patients are less likely to have access to health care or utilize health care for a variety of reasons, including stigma and fear of mistreatment. This often leads transgender individuals to present to care late in disease processes which makes their disease harder to treat and often leads to emergent medical conditions,” she added.

“Transgender men and women are at high risk for cardiovascular disease and often aren’t screened at recommended intervals because of decreased health care use compared to their cisgender counterparts,” she said. “This may lead to untreated diseases that make them even more likely to suffer poor health outcomes.”

The current study is important because there are “almost no prior data regarding the cardiovascular health status of this population prior to gender-affirming care,” Dr. Denby emphasized. “There are data that gay, lesbian, and bisexual individuals are at higher risk for poor cardiovascular outcomes, but the same data are lacking in the transgender group,” she said.

“As transgender individuals have frequent physician visits while on hormonal therapy, this seems like the opportune time to screen for cardiovascular risk factors and treat previously undiagnosed diseases that can lead to poor health outcomes in the future,” Dr. Denby explained. “If we are able to intervene at an earlier age, perhaps we can help prevent poor health outcomes down the road,” she said.
 

Additional research can inform practice

Dr. Denby said she was not surprised by the findings. “This is a very high-risk population that often doesn’t follow closely in the health care system,” she said. “These data are very important in thinking holistically about transgender patients.” Clinicians can “use the opportunities we have when they present for gender-affirming care to optimize their overall health status, promote long-term health, and reduce the risks associated with hormonal therapy and gender-affirming surgeries,” she noted. “We hope to use this information to change our practice at the Cleveland Clinic and nationally as well. Transgender patients should be screened and aggressively treated for cardiovascular disease and risk factors,” she said.

Key barriers to overcome include determining the best way to reach out to transgender individuals and then making them feel comfortable in the clinical setting, Dr. Denby said. “This means that we must set up clinics that are approachable and safe for all comers. The lack of laws in many states that protect this vulnerable population also contributes to lack of access to care,” she added. 

“We hope to continue research in this arena about how to effectively screen and treat transgender patients as they present to care, not only in the transgender clinic, but also to primary care providers (ob.gyn., internal medicine, family medicine, pediatrics) who also care for this population” since no specific guidelines currently exist to direct the screening for cardiovascular patients in particular, she said.
 

Findings offer foundation for LGBTQ cardiovascular studies

“This [study] provides us with a good rationale for why we should be considering cardiovascular health in transgender adults,” Billy A. Caceres, PhD, RN, of Columbia University School of Nursing, New York, said in an interview. “It is largely descriptive, but I think that that’s a good step in terms of at least understanding the magnitude of this problem. In addition, I think that what this abstract might do is help lead to future research that examines potentially the associations between not only gender-affirming hormone therapies but other potential social determinants like discrimination or poverty on the cardiovascular health of transgender people,” he noted.

Dr. Caceres served as chair of the writing group for the recent American Heart Association Scientific Statement: LGBTQ Heart Health published in Circulation. He had no financial conflicts to disclose.

The study received no outside funding. Dr. Denby had no financial conflicts to disclose.

SOURCE: Denby KJ et al. AHA 2020, Presentation P2274.

In a phase 3 trial where all participants received intensive behavior therapy, investigational 2.4-mg once-weekly subcutaneous semaglutide (Novo Nordisk) resulted in a 10.3% greater average weight loss than placebo over a period of 68 weeks.

If approved, this medication could be a “potential major breakthrough” in obesity management, the investigators suggested. But other experts urged caution, as cost and uptake are important considerations.
 

‘Potential weight loss that patients would be happy with’

Thomas A. Wadden, PhD, presented results from the study of 611 adults with overweight or obesity but no diabetes at the virtual ObesityWeek® Interactive 2020 meeting.

“Perhaps even more impressive was the finding that 75% of patients lost 10% or more of baseline body weight,” said Dr. Wadden, of the department of psychiatry at the University of Pennsylvania, Philadelphia.

Moreover, in this trial of semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist that is approved for treating type 2 diabetes at a weekly subcutaneous dose of 1 mg, but is being investigated at the higher dose for weight loss – 55% of patients lost ≥15% of their initial weight, and 36% lost ≥20% of their initial weight.

“These large categorical weight losses – particularly of 15% and 20% of initial weight – are potentially a major breakthrough in the management of obesity,” Dr. Wadden said in an interview.

Weight losses of this size, he added, “should confer greater improvements in cardiometabolic risk factors (such as hypertension, sleep apnea, and type 2 diabetes) as compared with losses of 5%-10% achieved with current behavioral or pharmacological approaches.” And patients are generally not satisfied with losses of less than 10% of initial weight when participating in intensive behavior programs or taking weight-loss medications.

Now, “the larger categorical weight losses will mean that a greater number of patients with obesity will be able to achieve a weight loss with which they are ... happy,” Dr. Wadden said in an interview.

According to Louis J. Aronne, MD, Weill Professor of Metabolic Research, Weill Cornell Medicine, New York, who is an investigator for another trial of semaglutide: “Even though it has the same mechanism of action [as liraglutide], the weight loss is two or more times greater [with semaglutide]. In my opinion, it’s really going to be a major advance in the treatment of obesity.”

In the discussion that followed the virtual presentation, one attendee asked about potential weight regain if a patient stopped taking the drug. Based on experience with another subcutaneous injectable GLP-1 receptor agonist, liraglutide (Saxenda), already approved for obesity, it may be that taking medicine for chronic overweight may become like taking a statin for elevated cholesterol, said Dr. Wadden.

Novo Nordisk has now completed the four trials in the STEP (Semaglutide Treatment Effect in People With Obesity) global phase 3 clinical development program, and plans to file applications with the Food and Drug Administration later this year and with the European Medicines Agency in early 2021 for review of semaglutide 2.4 mg for weight management.
 

“Fundamental issues need to be figured out”

Invited to comment, Scott Kahan, MD, said: “This is impressive data, confirming that semaglutide, particularly when used in concert with evidence-based counseling, is a highly effective agent for obesity management.”

However, “the real question, though, is what comes next,” stressed Dr. Kahan, director of the National Center for Weight and Wellness, Washington, DC.

“Will it be approved by the U.S. FDA? I believe so,” he said in an interview. “Yet we already have several effective obesity medications approved over the past decade – all of which are rarely used and therefore make little impact for patients in the real world.”

“Will there be insurance coverage, and therefore practical access for those who could most benefit?” he continued. “Will prescribers counsel their patients about obesity management, including the use of effective medications? Will patients utilize available options?”

“These and other fundamental issues must be figured out before we anoint any treatment option as a meaningful step forward, let alone a transformative development,” according to Dr. Kahan.

Similarly, Irl B. Hirsch, MD, stressed that, should this medication be approved for weight loss, cost would be a major factor in its uptake.

“I’m old enough to recall when we started using lovastatin in the late 1980s,” Dr. Hirsch, professor of medicine, University of Washington Medicine Diabetes Institute, Seattle, said in an interview.

“We used it without the type of evidence of statin use we have today. A pill, but in those days the statins were expensive. But over time, the evidence for statins grew and over the next 15 years it was quite clear that for both primary prevention (for those with diabetes) and secondary intervention these drugs needed to be used by millions of people. These recommendations became easier once the drugs became generic.

“Will the same thing happen for GLP-1 agonists? The problem is we need both ‘hard-outcome data’ [such as 3-point major adverse cardiovascular events] and more reasonable cost before we see this expanding to an entire population.

“In the future perhaps we could have a biosimilar GLP-1 agonist that would be more affordable than what we pay now, but even before that we need agreement from our reimbursement thought leaders that our society should reimburse these agents.

“My thinking now is the cost-benefit could be favorable, but this is all dependent on what happens to the cost of the drugs over time,” he said.
 

Additive effect of intensive behavior therapy plus medication

Dr. Wadden explained that intensive behavioral therapy “provides 14 or more counseling sessions in 6 months to modify diet and physical activity, through the patients’ use of behavioral strategies (such as keeping daily food and activity diaries).”

Such programs typically produce mean weight loss of 5%-8% of initial weight; less frequent (e.g., monthly) programs typically produce weight loss of only 1%-3%.

Prior studies suggest that intensive behavioral therapy and medication have additive effects. To investigate this, Dr. Wadden and colleagues randomized 611 adults (81% women) who were a mean age of 46 years and had a mean body mass index of 38 kg/m².

All participants received 30 intensive behavior therapy sessions provided by a registered dietitian (or other qualified provider), which typically lasted 20-30 minutes and were given weekly for 12 weeks, every other week for the next 12 weeks, and then monthly.  

The dietitian gave participants behavioral strategies to help them adhere to diet and physical activity goals.

During the first 8 weeks, participants were provided with a 1,000-1,200 kcal/day meal replacement diet that included liquid shakes, meal bars, and prepared entrees designed to facilitate a large initial weight loss.

They then transitioned to a diet of conventional foods (of their choosing), with a goal of 1,200-1,800 kcal/day based on body weight.  

The physical activity goal was 100 minutes/week of walking or other aerobic activity in the first month, building up to 200 minutes/week by month 6.
 

‘More effective than current FDA-approved weight-loss medications’

At week 68, mean body weight decreased from baseline by 16.0% in the semaglutide group versus 5.7% in the placebo group (P < .0001).

In this trial, where all participants received extensive intensive behavior therapy, more participants had weight loss ≥5%, ≥10%, ≥15%, and ≥20% of their initial weight with semaglutide versus placebo (87% vs. 48%; 75% vs. 27%; 56% vs. 13%; 36% vs. 4%, respectively; all P < .0001).

From baseline to week 68, the proportion of participants with prediabetes decreased from 48% to 7% in the semaglutide group and from 53% to 26% in the placebo group.

Patients who received semaglutide had greater improvements in lipids, too.

Although the weight loss was 10.3% (10.6 kg) greater with semaglutide, Dr. Wadden noted, “additional studies have shown this net benefit to be as great as 11%-12%, which would make semaglutide 2.4 mg more effective than current [FDA-approved] weight-loss medications.”

“Naltrexone-bupropion (Contrave) with lifestyle counseling, for example,” he continued, “produces a loss that is 5 kg greater than lifestyle counseling plus placebo, liraglutide 3.0 mg (Saxenda) a loss 5.3 kg greater than placebo, and phentermine-topiramate (Qsymia) a loss that is 8.8 kg greater than placebo.” 

Semaglutide was well tolerated. Gastrointestinal adverse events, the most common type, occurred in 83% of patients in the semaglutide group and 63% of patients in the placebo group.

Nausea, as well as constipation and diarrhea, are common in medications that increase GLP-1 levels, Dr. Wadden noted. Side effects can be managed by slowly increasing the medication dose over 4 months.  

Dr. Wadden expects that, if approved, semaglutide 2.4 mg subcutaneous once-weekly will be recommended as an adjunct to a reduced calorie diet and increased physical activity. Additional studies suggest that monthly counseling should be sufficient to obtain similar weight losses as those seen in the current trial, which had more intensive counseling.

As well as being approved as a weekly subcutaneous injectable treatment for type 2 diabetes, semaglutide is also approved as an once-daily oral agent for the same indication (Rybelsus, Novo Nordisk) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.

Dr. Wadden serves on scientific advisory boards for Novo Nordisk and WW (formerly Weight Watchers), and has received grant support, on behalf of the University of Pennsylvania, from Novo Nordisk. Dr. Aronne is an investigator in a long-term trial of semaglutide and has served on scientific advisory boards for Novo Nordisk in the past. He also has other industry relationships that are not related to semaglutide.

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

In a phase 3 trial where all participants received intensive behavior therapy, investigational 2.4-mg once-weekly subcutaneous semaglutide (Novo Nordisk) resulted in a 10.3% greater average weight loss than placebo over a period of 68 weeks.

If approved, this medication could be a “potential major breakthrough” in obesity management, the investigators suggested. But other experts urged caution, as cost and uptake are important considerations.
 

‘Potential weight loss that patients would be happy with’

Thomas A. Wadden, PhD, presented results from the study of 611 adults with overweight or obesity but no diabetes at the virtual ObesityWeek® Interactive 2020 meeting.

“Perhaps even more impressive was the finding that 75% of patients lost 10% or more of baseline body weight,” said Dr. Wadden, of the department of psychiatry at the University of Pennsylvania, Philadelphia.

Moreover, in this trial of semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist that is approved for treating type 2 diabetes at a weekly subcutaneous dose of 1 mg, but is being investigated at the higher dose for weight loss – 55% of patients lost ≥15% of their initial weight, and 36% lost ≥20% of their initial weight.

“These large categorical weight losses – particularly of 15% and 20% of initial weight – are potentially a major breakthrough in the management of obesity,” Dr. Wadden said in an interview.

Weight losses of this size, he added, “should confer greater improvements in cardiometabolic risk factors (such as hypertension, sleep apnea, and type 2 diabetes) as compared with losses of 5%-10% achieved with current behavioral or pharmacological approaches.” And patients are generally not satisfied with losses of less than 10% of initial weight when participating in intensive behavior programs or taking weight-loss medications.

Now, “the larger categorical weight losses will mean that a greater number of patients with obesity will be able to achieve a weight loss with which they are ... happy,” Dr. Wadden said in an interview.

According to Louis J. Aronne, MD, Weill Professor of Metabolic Research, Weill Cornell Medicine, New York, who is an investigator for another trial of semaglutide: “Even though it has the same mechanism of action [as liraglutide], the weight loss is two or more times greater [with semaglutide]. In my opinion, it’s really going to be a major advance in the treatment of obesity.”

In the discussion that followed the virtual presentation, one attendee asked about potential weight regain if a patient stopped taking the drug. Based on experience with another subcutaneous injectable GLP-1 receptor agonist, liraglutide (Saxenda), already approved for obesity, it may be that taking medicine for chronic overweight may become like taking a statin for elevated cholesterol, said Dr. Wadden.

Novo Nordisk has now completed the four trials in the STEP (Semaglutide Treatment Effect in People With Obesity) global phase 3 clinical development program, and plans to file applications with the Food and Drug Administration later this year and with the European Medicines Agency in early 2021 for review of semaglutide 2.4 mg for weight management.
 

“Fundamental issues need to be figured out”

Invited to comment, Scott Kahan, MD, said: “This is impressive data, confirming that semaglutide, particularly when used in concert with evidence-based counseling, is a highly effective agent for obesity management.”

However, “the real question, though, is what comes next,” stressed Dr. Kahan, director of the National Center for Weight and Wellness, Washington, DC.

“Will it be approved by the U.S. FDA? I believe so,” he said in an interview. “Yet we already have several effective obesity medications approved over the past decade – all of which are rarely used and therefore make little impact for patients in the real world.”

“Will there be insurance coverage, and therefore practical access for those who could most benefit?” he continued. “Will prescribers counsel their patients about obesity management, including the use of effective medications? Will patients utilize available options?”

“These and other fundamental issues must be figured out before we anoint any treatment option as a meaningful step forward, let alone a transformative development,” according to Dr. Kahan.

Similarly, Irl B. Hirsch, MD, stressed that, should this medication be approved for weight loss, cost would be a major factor in its uptake.

“I’m old enough to recall when we started using lovastatin in the late 1980s,” Dr. Hirsch, professor of medicine, University of Washington Medicine Diabetes Institute, Seattle, said in an interview.

“We used it without the type of evidence of statin use we have today. A pill, but in those days the statins were expensive. But over time, the evidence for statins grew and over the next 15 years it was quite clear that for both primary prevention (for those with diabetes) and secondary intervention these drugs needed to be used by millions of people. These recommendations became easier once the drugs became generic.

“Will the same thing happen for GLP-1 agonists? The problem is we need both ‘hard-outcome data’ [such as 3-point major adverse cardiovascular events] and more reasonable cost before we see this expanding to an entire population.

“In the future perhaps we could have a biosimilar GLP-1 agonist that would be more affordable than what we pay now, but even before that we need agreement from our reimbursement thought leaders that our society should reimburse these agents.

“My thinking now is the cost-benefit could be favorable, but this is all dependent on what happens to the cost of the drugs over time,” he said.
 

Additive effect of intensive behavior therapy plus medication

Dr. Wadden explained that intensive behavioral therapy “provides 14 or more counseling sessions in 6 months to modify diet and physical activity, through the patients’ use of behavioral strategies (such as keeping daily food and activity diaries).”

Such programs typically produce mean weight loss of 5%-8% of initial weight; less frequent (e.g., monthly) programs typically produce weight loss of only 1%-3%.

Prior studies suggest that intensive behavioral therapy and medication have additive effects. To investigate this, Dr. Wadden and colleagues randomized 611 adults (81% women) who were a mean age of 46 years and had a mean body mass index of 38 kg/m².

All participants received 30 intensive behavior therapy sessions provided by a registered dietitian (or other qualified provider), which typically lasted 20-30 minutes and were given weekly for 12 weeks, every other week for the next 12 weeks, and then monthly.  

The dietitian gave participants behavioral strategies to help them adhere to diet and physical activity goals.

During the first 8 weeks, participants were provided with a 1,000-1,200 kcal/day meal replacement diet that included liquid shakes, meal bars, and prepared entrees designed to facilitate a large initial weight loss.

They then transitioned to a diet of conventional foods (of their choosing), with a goal of 1,200-1,800 kcal/day based on body weight.  

The physical activity goal was 100 minutes/week of walking or other aerobic activity in the first month, building up to 200 minutes/week by month 6.
 

‘More effective than current FDA-approved weight-loss medications’

At week 68, mean body weight decreased from baseline by 16.0% in the semaglutide group versus 5.7% in the placebo group (P < .0001).

In this trial, where all participants received extensive intensive behavior therapy, more participants had weight loss ≥5%, ≥10%, ≥15%, and ≥20% of their initial weight with semaglutide versus placebo (87% vs. 48%; 75% vs. 27%; 56% vs. 13%; 36% vs. 4%, respectively; all P < .0001).

From baseline to week 68, the proportion of participants with prediabetes decreased from 48% to 7% in the semaglutide group and from 53% to 26% in the placebo group.

Patients who received semaglutide had greater improvements in lipids, too.

Although the weight loss was 10.3% (10.6 kg) greater with semaglutide, Dr. Wadden noted, “additional studies have shown this net benefit to be as great as 11%-12%, which would make semaglutide 2.4 mg more effective than current [FDA-approved] weight-loss medications.”

“Naltrexone-bupropion (Contrave) with lifestyle counseling, for example,” he continued, “produces a loss that is 5 kg greater than lifestyle counseling plus placebo, liraglutide 3.0 mg (Saxenda) a loss 5.3 kg greater than placebo, and phentermine-topiramate (Qsymia) a loss that is 8.8 kg greater than placebo.” 

Semaglutide was well tolerated. Gastrointestinal adverse events, the most common type, occurred in 83% of patients in the semaglutide group and 63% of patients in the placebo group.

Nausea, as well as constipation and diarrhea, are common in medications that increase GLP-1 levels, Dr. Wadden noted. Side effects can be managed by slowly increasing the medication dose over 4 months.  

Dr. Wadden expects that, if approved, semaglutide 2.4 mg subcutaneous once-weekly will be recommended as an adjunct to a reduced calorie diet and increased physical activity. Additional studies suggest that monthly counseling should be sufficient to obtain similar weight losses as those seen in the current trial, which had more intensive counseling.

As well as being approved as a weekly subcutaneous injectable treatment for type 2 diabetes, semaglutide is also approved as an once-daily oral agent for the same indication (Rybelsus, Novo Nordisk) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.

Dr. Wadden serves on scientific advisory boards for Novo Nordisk and WW (formerly Weight Watchers), and has received grant support, on behalf of the University of Pennsylvania, from Novo Nordisk. Dr. Aronne is an investigator in a long-term trial of semaglutide and has served on scientific advisory boards for Novo Nordisk in the past. He also has other industry relationships that are not related to semaglutide.

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

In a phase 3 trial where all participants received intensive behavior therapy, investigational 2.4-mg once-weekly subcutaneous semaglutide (Novo Nordisk) resulted in a 10.3% greater average weight loss than placebo over a period of 68 weeks.

If approved, this medication could be a “potential major breakthrough” in obesity management, the investigators suggested. But other experts urged caution, as cost and uptake are important considerations.
 

‘Potential weight loss that patients would be happy with’

Thomas A. Wadden, PhD, presented results from the study of 611 adults with overweight or obesity but no diabetes at the virtual ObesityWeek® Interactive 2020 meeting.

“Perhaps even more impressive was the finding that 75% of patients lost 10% or more of baseline body weight,” said Dr. Wadden, of the department of psychiatry at the University of Pennsylvania, Philadelphia.

Moreover, in this trial of semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist that is approved for treating type 2 diabetes at a weekly subcutaneous dose of 1 mg, but is being investigated at the higher dose for weight loss – 55% of patients lost ≥15% of their initial weight, and 36% lost ≥20% of their initial weight.

“These large categorical weight losses – particularly of 15% and 20% of initial weight – are potentially a major breakthrough in the management of obesity,” Dr. Wadden said in an interview.

Weight losses of this size, he added, “should confer greater improvements in cardiometabolic risk factors (such as hypertension, sleep apnea, and type 2 diabetes) as compared with losses of 5%-10% achieved with current behavioral or pharmacological approaches.” And patients are generally not satisfied with losses of less than 10% of initial weight when participating in intensive behavior programs or taking weight-loss medications.

Now, “the larger categorical weight losses will mean that a greater number of patients with obesity will be able to achieve a weight loss with which they are ... happy,” Dr. Wadden said in an interview.

According to Louis J. Aronne, MD, Weill Professor of Metabolic Research, Weill Cornell Medicine, New York, who is an investigator for another trial of semaglutide: “Even though it has the same mechanism of action [as liraglutide], the weight loss is two or more times greater [with semaglutide]. In my opinion, it’s really going to be a major advance in the treatment of obesity.”

In the discussion that followed the virtual presentation, one attendee asked about potential weight regain if a patient stopped taking the drug. Based on experience with another subcutaneous injectable GLP-1 receptor agonist, liraglutide (Saxenda), already approved for obesity, it may be that taking medicine for chronic overweight may become like taking a statin for elevated cholesterol, said Dr. Wadden.

Novo Nordisk has now completed the four trials in the STEP (Semaglutide Treatment Effect in People With Obesity) global phase 3 clinical development program, and plans to file applications with the Food and Drug Administration later this year and with the European Medicines Agency in early 2021 for review of semaglutide 2.4 mg for weight management.
 

“Fundamental issues need to be figured out”

Invited to comment, Scott Kahan, MD, said: “This is impressive data, confirming that semaglutide, particularly when used in concert with evidence-based counseling, is a highly effective agent for obesity management.”

However, “the real question, though, is what comes next,” stressed Dr. Kahan, director of the National Center for Weight and Wellness, Washington, DC.

“Will it be approved by the U.S. FDA? I believe so,” he said in an interview. “Yet we already have several effective obesity medications approved over the past decade – all of which are rarely used and therefore make little impact for patients in the real world.”

“Will there be insurance coverage, and therefore practical access for those who could most benefit?” he continued. “Will prescribers counsel their patients about obesity management, including the use of effective medications? Will patients utilize available options?”

“These and other fundamental issues must be figured out before we anoint any treatment option as a meaningful step forward, let alone a transformative development,” according to Dr. Kahan.

Similarly, Irl B. Hirsch, MD, stressed that, should this medication be approved for weight loss, cost would be a major factor in its uptake.

“I’m old enough to recall when we started using lovastatin in the late 1980s,” Dr. Hirsch, professor of medicine, University of Washington Medicine Diabetes Institute, Seattle, said in an interview.

“We used it without the type of evidence of statin use we have today. A pill, but in those days the statins were expensive. But over time, the evidence for statins grew and over the next 15 years it was quite clear that for both primary prevention (for those with diabetes) and secondary intervention these drugs needed to be used by millions of people. These recommendations became easier once the drugs became generic.

“Will the same thing happen for GLP-1 agonists? The problem is we need both ‘hard-outcome data’ [such as 3-point major adverse cardiovascular events] and more reasonable cost before we see this expanding to an entire population.

“In the future perhaps we could have a biosimilar GLP-1 agonist that would be more affordable than what we pay now, but even before that we need agreement from our reimbursement thought leaders that our society should reimburse these agents.

“My thinking now is the cost-benefit could be favorable, but this is all dependent on what happens to the cost of the drugs over time,” he said.
 

Additive effect of intensive behavior therapy plus medication

Dr. Wadden explained that intensive behavioral therapy “provides 14 or more counseling sessions in 6 months to modify diet and physical activity, through the patients’ use of behavioral strategies (such as keeping daily food and activity diaries).”

Such programs typically produce mean weight loss of 5%-8% of initial weight; less frequent (e.g., monthly) programs typically produce weight loss of only 1%-3%.

Prior studies suggest that intensive behavioral therapy and medication have additive effects. To investigate this, Dr. Wadden and colleagues randomized 611 adults (81% women) who were a mean age of 46 years and had a mean body mass index of 38 kg/m².

All participants received 30 intensive behavior therapy sessions provided by a registered dietitian (or other qualified provider), which typically lasted 20-30 minutes and were given weekly for 12 weeks, every other week for the next 12 weeks, and then monthly.  

The dietitian gave participants behavioral strategies to help them adhere to diet and physical activity goals.

During the first 8 weeks, participants were provided with a 1,000-1,200 kcal/day meal replacement diet that included liquid shakes, meal bars, and prepared entrees designed to facilitate a large initial weight loss.

They then transitioned to a diet of conventional foods (of their choosing), with a goal of 1,200-1,800 kcal/day based on body weight.  

The physical activity goal was 100 minutes/week of walking or other aerobic activity in the first month, building up to 200 minutes/week by month 6.
 

‘More effective than current FDA-approved weight-loss medications’

At week 68, mean body weight decreased from baseline by 16.0% in the semaglutide group versus 5.7% in the placebo group (P < .0001).

In this trial, where all participants received extensive intensive behavior therapy, more participants had weight loss ≥5%, ≥10%, ≥15%, and ≥20% of their initial weight with semaglutide versus placebo (87% vs. 48%; 75% vs. 27%; 56% vs. 13%; 36% vs. 4%, respectively; all P < .0001).

From baseline to week 68, the proportion of participants with prediabetes decreased from 48% to 7% in the semaglutide group and from 53% to 26% in the placebo group.

Patients who received semaglutide had greater improvements in lipids, too.

Although the weight loss was 10.3% (10.6 kg) greater with semaglutide, Dr. Wadden noted, “additional studies have shown this net benefit to be as great as 11%-12%, which would make semaglutide 2.4 mg more effective than current [FDA-approved] weight-loss medications.”

“Naltrexone-bupropion (Contrave) with lifestyle counseling, for example,” he continued, “produces a loss that is 5 kg greater than lifestyle counseling plus placebo, liraglutide 3.0 mg (Saxenda) a loss 5.3 kg greater than placebo, and phentermine-topiramate (Qsymia) a loss that is 8.8 kg greater than placebo.” 

Semaglutide was well tolerated. Gastrointestinal adverse events, the most common type, occurred in 83% of patients in the semaglutide group and 63% of patients in the placebo group.

Nausea, as well as constipation and diarrhea, are common in medications that increase GLP-1 levels, Dr. Wadden noted. Side effects can be managed by slowly increasing the medication dose over 4 months.  

Dr. Wadden expects that, if approved, semaglutide 2.4 mg subcutaneous once-weekly will be recommended as an adjunct to a reduced calorie diet and increased physical activity. Additional studies suggest that monthly counseling should be sufficient to obtain similar weight losses as those seen in the current trial, which had more intensive counseling.

As well as being approved as a weekly subcutaneous injectable treatment for type 2 diabetes, semaglutide is also approved as an once-daily oral agent for the same indication (Rybelsus, Novo Nordisk) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.

Dr. Wadden serves on scientific advisory boards for Novo Nordisk and WW (formerly Weight Watchers), and has received grant support, on behalf of the University of Pennsylvania, from Novo Nordisk. Dr. Aronne is an investigator in a long-term trial of semaglutide and has served on scientific advisory boards for Novo Nordisk in the past. He also has other industry relationships that are not related to semaglutide.

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

Almost 60% of patients with biopsy-confirmed nonalcoholic steatohepatitis and liver fibrosis showed resolution of NASH after treatment with semaglutide, according to a phase 2, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine and presented at the 2020 American Association for the Study of Liver Diseases (AASLD) meeting.

“This bodes well for further study of semaglutide and is supported further by marked improvements in weight, glycemic control and lipid profile,” commented the study’s senior author Philip N. Newsome, PhD, FRCPE, of the University of Birmingham (England), in an interview.

The highest daily dose (0.4 mg) of the glucagonlike peptide-1 (GLP-1) receptor agonist, semaglutide, which is approved for the treatment of type 2 diabetes, led to levels of NASH resolution “which are higher than any previously demonstrated,” noted Dr. Newsome. “This was also accompanied by improvement in noninvasive markers of liver fibrosis and also less fibrosis progression, compared to placebo.”

“I think this represents an exciting advance and will, if confirmed in further studies, mark a step-change in our management of patients with NASH,” he added.

The multicenter study, conducted at 143 sites in 16 countries, included 320 patients, aged 18-75 years, with or without type 2 diabetes, who had histologic evidence of NASH and stage 1-3 liver fibrosis.

They were randomized in a 3:3:3:1:1:1 ratio to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg, or placebo for 72 weeks.

The primary endpoint was resolution of NASH and no worsening of fibrosis, with a secondary endpoint being improvement of fibrosis by at least one stage without worsening of NASH.

The study found 40% of patients in the 0.1-mg semaglutide group, 36% in the 0.2-mg group, and 59% in the 0.4-mg group achieved NASH resolution with no worsening of fibrosis, compared with 17% of the placebo group (odds ratio, 6.87; P < .001 for the highest semaglutide dose). However, the treatment did not lead to significant between-group differences in the secondary endpoint, which occurred in 43% of patients on the highest semaglutide dose compared to 33% in the placebo group (OR, 1.42; P = .48).

Treatment with semaglutide also resulted in dose-dependent reductions in body weight, as well as in glycated hemoglobin levels. Bodyweight was reduced by a mean of 5% in the 0.1-mg semaglutide group, followed by mean reductions of 9% and 13% in the 0.2-mg and 0.4-mg groups respectively. This compared to a mean reduction of 1% in the placebo group.

Similarly, glycated hemoglobin levels among patients with type 2 diabetes dropped by 0.63, 1.07, and 1.15 percentage points in the 0.1-mg, 0.2-mg, and 0.4-mg semaglutide groups respectively, compared with a drop of 0.01 percentage point in the placebo group.

“The fact that the percentage of patients who had an improvement in fibrosis stage was not significantly higher with semaglutide than with placebo – despite a greater benefit with respect to NASH resolution and dose-dependent weight loss – was unexpected, given that previous studies have suggested that resolution of NASH and improvements in activity scores for the components of nonalcoholic fatty liver disease are associated with regression of fibrosis,” wrote the authors. “However, the temporal association among NASH resolution, weight loss, and improvement in fibrosis stage is not fully understood. It is possible that the current trial was not of sufficient duration for improvements in fibrosis stage to become apparent.”

The authors also noted that the safety profile of semaglutide was “consistent with that observed in patients with type 2 diabetes in other trials and with the known effects of GLP-1 receptor agonists,” with gastrointestinal disorders being the most commonly reported.

Nausea, constipation, and vomiting were reported more often in the 0.4-mg semaglutide group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%).

The overall incidence of benign, malignant, or unspecified neoplasms was 15% in the treatment groups versus 8% in the placebo group.

Rowen K. Zetterman, MD, who was not involved with the study, noted that “treatment of NASH is currently limited, and no therapies have yet been approved by the Food and Drug Administration.”

The findings are “important but not yet exciting,” added Dr. Zetterman, who is professor emeritus of internal medicine and associate vice chancellor for strategic planning for the University of Nebraska Medical Center, Omaha.

“Though reversal of liver fibrosis was not noted, the resolution of hepatic inflammation and liver cell injury by semaglutide suggests it may be slowing disease progression,” said Dr. Zetterman, who also serves on the editorial advisory board of Internal Medicine News. This “warrants additional studies where longer treatment with semaglutide may prove reversal of fibrosis and/or prevention of progression to cirrhosis.”

The study was sponsored by Novo Nordisk. Dr. Newsome reported disclosures related to Novo Nordisk during the conduct of the study, and to Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead, Pfizer, Pharmaxis, and Poxel. Several of the other study authors reported receiving fees and grants from various pharmaceutical companies, including Novo Nordisk One author reported pending patents for the use of semaglutide. Dr. Zetterman had no relevant disclosures.

SOURCE: Newsome PN et al. N Engl J Med. 2020 Nov 13. doi: 10.1056/NEJMoa2028395.

Almost 60% of patients with biopsy-confirmed nonalcoholic steatohepatitis and liver fibrosis showed resolution of NASH after treatment with semaglutide, according to a phase 2, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine and presented at the 2020 American Association for the Study of Liver Diseases (AASLD) meeting.

“This bodes well for further study of semaglutide and is supported further by marked improvements in weight, glycemic control and lipid profile,” commented the study’s senior author Philip N. Newsome, PhD, FRCPE, of the University of Birmingham (England), in an interview.

The highest daily dose (0.4 mg) of the glucagonlike peptide-1 (GLP-1) receptor agonist, semaglutide, which is approved for the treatment of type 2 diabetes, led to levels of NASH resolution “which are higher than any previously demonstrated,” noted Dr. Newsome. “This was also accompanied by improvement in noninvasive markers of liver fibrosis and also less fibrosis progression, compared to placebo.”

“I think this represents an exciting advance and will, if confirmed in further studies, mark a step-change in our management of patients with NASH,” he added.

The multicenter study, conducted at 143 sites in 16 countries, included 320 patients, aged 18-75 years, with or without type 2 diabetes, who had histologic evidence of NASH and stage 1-3 liver fibrosis.

They were randomized in a 3:3:3:1:1:1 ratio to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg, or placebo for 72 weeks.

The primary endpoint was resolution of NASH and no worsening of fibrosis, with a secondary endpoint being improvement of fibrosis by at least one stage without worsening of NASH.

The study found 40% of patients in the 0.1-mg semaglutide group, 36% in the 0.2-mg group, and 59% in the 0.4-mg group achieved NASH resolution with no worsening of fibrosis, compared with 17% of the placebo group (odds ratio, 6.87; P < .001 for the highest semaglutide dose). However, the treatment did not lead to significant between-group differences in the secondary endpoint, which occurred in 43% of patients on the highest semaglutide dose compared to 33% in the placebo group (OR, 1.42; P = .48).

Treatment with semaglutide also resulted in dose-dependent reductions in body weight, as well as in glycated hemoglobin levels. Bodyweight was reduced by a mean of 5% in the 0.1-mg semaglutide group, followed by mean reductions of 9% and 13% in the 0.2-mg and 0.4-mg groups respectively. This compared to a mean reduction of 1% in the placebo group.

Similarly, glycated hemoglobin levels among patients with type 2 diabetes dropped by 0.63, 1.07, and 1.15 percentage points in the 0.1-mg, 0.2-mg, and 0.4-mg semaglutide groups respectively, compared with a drop of 0.01 percentage point in the placebo group.

“The fact that the percentage of patients who had an improvement in fibrosis stage was not significantly higher with semaglutide than with placebo – despite a greater benefit with respect to NASH resolution and dose-dependent weight loss – was unexpected, given that previous studies have suggested that resolution of NASH and improvements in activity scores for the components of nonalcoholic fatty liver disease are associated with regression of fibrosis,” wrote the authors. “However, the temporal association among NASH resolution, weight loss, and improvement in fibrosis stage is not fully understood. It is possible that the current trial was not of sufficient duration for improvements in fibrosis stage to become apparent.”

The authors also noted that the safety profile of semaglutide was “consistent with that observed in patients with type 2 diabetes in other trials and with the known effects of GLP-1 receptor agonists,” with gastrointestinal disorders being the most commonly reported.

Nausea, constipation, and vomiting were reported more often in the 0.4-mg semaglutide group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%).

The overall incidence of benign, malignant, or unspecified neoplasms was 15% in the treatment groups versus 8% in the placebo group.

Rowen K. Zetterman, MD, who was not involved with the study, noted that “treatment of NASH is currently limited, and no therapies have yet been approved by the Food and Drug Administration.”

The findings are “important but not yet exciting,” added Dr. Zetterman, who is professor emeritus of internal medicine and associate vice chancellor for strategic planning for the University of Nebraska Medical Center, Omaha.

“Though reversal of liver fibrosis was not noted, the resolution of hepatic inflammation and liver cell injury by semaglutide suggests it may be slowing disease progression,” said Dr. Zetterman, who also serves on the editorial advisory board of Internal Medicine News. This “warrants additional studies where longer treatment with semaglutide may prove reversal of fibrosis and/or prevention of progression to cirrhosis.”

The study was sponsored by Novo Nordisk. Dr. Newsome reported disclosures related to Novo Nordisk during the conduct of the study, and to Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead, Pfizer, Pharmaxis, and Poxel. Several of the other study authors reported receiving fees and grants from various pharmaceutical companies, including Novo Nordisk One author reported pending patents for the use of semaglutide. Dr. Zetterman had no relevant disclosures.

SOURCE: Newsome PN et al. N Engl J Med. 2020 Nov 13. doi: 10.1056/NEJMoa2028395.

Almost 60% of patients with biopsy-confirmed nonalcoholic steatohepatitis and liver fibrosis showed resolution of NASH after treatment with semaglutide, according to a phase 2, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine and presented at the 2020 American Association for the Study of Liver Diseases (AASLD) meeting.

“This bodes well for further study of semaglutide and is supported further by marked improvements in weight, glycemic control and lipid profile,” commented the study’s senior author Philip N. Newsome, PhD, FRCPE, of the University of Birmingham (England), in an interview.

The highest daily dose (0.4 mg) of the glucagonlike peptide-1 (GLP-1) receptor agonist, semaglutide, which is approved for the treatment of type 2 diabetes, led to levels of NASH resolution “which are higher than any previously demonstrated,” noted Dr. Newsome. “This was also accompanied by improvement in noninvasive markers of liver fibrosis and also less fibrosis progression, compared to placebo.”

“I think this represents an exciting advance and will, if confirmed in further studies, mark a step-change in our management of patients with NASH,” he added.

The multicenter study, conducted at 143 sites in 16 countries, included 320 patients, aged 18-75 years, with or without type 2 diabetes, who had histologic evidence of NASH and stage 1-3 liver fibrosis.

They were randomized in a 3:3:3:1:1:1 ratio to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg, or placebo for 72 weeks.

The primary endpoint was resolution of NASH and no worsening of fibrosis, with a secondary endpoint being improvement of fibrosis by at least one stage without worsening of NASH.

The study found 40% of patients in the 0.1-mg semaglutide group, 36% in the 0.2-mg group, and 59% in the 0.4-mg group achieved NASH resolution with no worsening of fibrosis, compared with 17% of the placebo group (odds ratio, 6.87; P < .001 for the highest semaglutide dose). However, the treatment did not lead to significant between-group differences in the secondary endpoint, which occurred in 43% of patients on the highest semaglutide dose compared to 33% in the placebo group (OR, 1.42; P = .48).

Treatment with semaglutide also resulted in dose-dependent reductions in body weight, as well as in glycated hemoglobin levels. Bodyweight was reduced by a mean of 5% in the 0.1-mg semaglutide group, followed by mean reductions of 9% and 13% in the 0.2-mg and 0.4-mg groups respectively. This compared to a mean reduction of 1% in the placebo group.

Similarly, glycated hemoglobin levels among patients with type 2 diabetes dropped by 0.63, 1.07, and 1.15 percentage points in the 0.1-mg, 0.2-mg, and 0.4-mg semaglutide groups respectively, compared with a drop of 0.01 percentage point in the placebo group.

“The fact that the percentage of patients who had an improvement in fibrosis stage was not significantly higher with semaglutide than with placebo – despite a greater benefit with respect to NASH resolution and dose-dependent weight loss – was unexpected, given that previous studies have suggested that resolution of NASH and improvements in activity scores for the components of nonalcoholic fatty liver disease are associated with regression of fibrosis,” wrote the authors. “However, the temporal association among NASH resolution, weight loss, and improvement in fibrosis stage is not fully understood. It is possible that the current trial was not of sufficient duration for improvements in fibrosis stage to become apparent.”

The authors also noted that the safety profile of semaglutide was “consistent with that observed in patients with type 2 diabetes in other trials and with the known effects of GLP-1 receptor agonists,” with gastrointestinal disorders being the most commonly reported.

Nausea, constipation, and vomiting were reported more often in the 0.4-mg semaglutide group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%).

The overall incidence of benign, malignant, or unspecified neoplasms was 15% in the treatment groups versus 8% in the placebo group.

Rowen K. Zetterman, MD, who was not involved with the study, noted that “treatment of NASH is currently limited, and no therapies have yet been approved by the Food and Drug Administration.”

The findings are “important but not yet exciting,” added Dr. Zetterman, who is professor emeritus of internal medicine and associate vice chancellor for strategic planning for the University of Nebraska Medical Center, Omaha.

“Though reversal of liver fibrosis was not noted, the resolution of hepatic inflammation and liver cell injury by semaglutide suggests it may be slowing disease progression,” said Dr. Zetterman, who also serves on the editorial advisory board of Internal Medicine News. This “warrants additional studies where longer treatment with semaglutide may prove reversal of fibrosis and/or prevention of progression to cirrhosis.”

The study was sponsored by Novo Nordisk. Dr. Newsome reported disclosures related to Novo Nordisk during the conduct of the study, and to Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead, Pfizer, Pharmaxis, and Poxel. Several of the other study authors reported receiving fees and grants from various pharmaceutical companies, including Novo Nordisk One author reported pending patents for the use of semaglutide. Dr. Zetterman had no relevant disclosures.

SOURCE: Newsome PN et al. N Engl J Med. 2020 Nov 13. doi: 10.1056/NEJMoa2028395.

Coronavirus infections are expected to continue to climb in the upper Midwest and intermountain West of the United States, which will strain an already-maxed-out system as increased hospitalizations and deaths follow, say infectious diseases specialists.

“I think the situation in 2 to 4 weeks is going to be grim,” said Andrew Pavia, MD, chief of the division of pediatric infectious diseases at the University of Utah School of Medicine in Salt Lake City, on a call yesterday with reporters, sponsored by the Infectious Diseases Society of America (IDSA).

Cases began rising in Utah in mid-September and have gone up steeply since, increasing from 450 cases per day to 2,650 reported on Nov. 8, according to the Johns Hopkins Coronavirus Resource Center. The New York Times reports that the 7-day rolling average for hospitalizations have gone up 34% and deaths have risen 93%, with 11 deaths this past Tuesday.

Other states in the west – Montana, Idaho, and Wyoming, which reported 1,232 cases on Tuesday and have been averaging 660 cases a day in the last week, according to the Times – are being equally hard hit. The same is true for states in the upper Midwest, including North Dakota, South Dakota, Minnesota, Wisconsin, and Iowa.

Most of the states being hit now have large swaths of rural countryside, which means health resources are limited and spread out, said Pavia.

“The situation really has to be described as dire,” said Pavia, noting that intensive care units in Utah are full, including contingency units that were purpose-built for the pandemic. Physicians and nurses are burned out and in short supply, he said. Instead of a 1:1 or 1:2 nurse-to-ICU patient ratio, the ratio is now 1:4, said Pavia. “Throughout the region, people are facing a crisis in staffing.”

The University of Utah hospital normally takes referrals from Idaho, Wyoming, and northern Arizona, but is prioritizing Utah residents for ICU admission, said Pavia.

Both Pavia and Daniel P. McQuillen, MD, president-elect of IDSA, also noted the shortage of infectious diseases specialists, which began at least a decade ago. McQuillen, senior infectious diseases physician at Beth Israel Lahey Health in Boston, said he and colleagues had done some research earlier this year anticipating the pandemic’s spread, and found that some 80% of counties – including the rural counties in the states now being hit – have one or zero infectious disease specialists.

Those specialists can help improve patient outcomes, explained McQuillen.
 

Colleges likely driving spike

Pavia said the reasons for sharp increases in the region vary, but there are several areas of commonality. Most of the states didn’t have many cases early in the pandemic, “so perhaps there was less fear of the virus.” There were fewer actions by government officials, driven perhaps by the reluctance to take on individuals who are distrustful of government, he said.

Cases started going up after some events – such as the August motorcycle rally in Sturgis, South Dakota – but the acceleration in September was likely driven by the reopening of colleges across the region, said Pavia.

“Most of the states have kept in-person schooling, and probably more importantly, they’ve kept extracurricular activities in sports,” he said, adding that in many of the areas the weather has turned cooler, driving people indoors.

McQuillen said it has been shown that a significant amount of transmission occurs within homes – and college students may be bringing the virus home and fueling spread, in addition to people not wearing masks while at small family gatherings.

Both he and Pavia said more emphasis needs to be placed on mitigation measures such as mask-wearing as well as on testing. IDSA is starting #MaskUpAmerica, a public service campaign aimed at getting people to wear masks in all community settings, including at work, in churches, at social gatherings, in gyms, and on public transportation.

Pavia said in some places people are refusing to be tested because they don’t want to be quarantined.

Utah Gov. Gary Herbert (R) issued a statewide mask mandate this past weekend and announced some other restrictions, including a 2-week pause on most, but not all, athletic events, according to CBS News. But local pushback could weaken those measures, said Pavia.

Many people are looking to vaccines to usher in a return to normal. But, said Pavia, “vaccines aren’t going to help us out much this winter,” noting that initial doses will be given mostly to first responders and healthcare workers.

“The only way we’re going to get out of this this winter is by doing the things that we’ve been talking about for months – wearing a mask, watching your social distance, and avoiding large gatherings,” he said.

There is an end in sight, said Pavia, but it won’t be in early 2021. “That end is next summer or fall,” he said. “And that’s a hard message to give but it’s really critical.”

McQuillen agreed: “Wearing masks and distancing are exactly all we have probably until middle of next year.”
 

This article first appeared on Medscape.com.

Coronavirus infections are expected to continue to climb in the upper Midwest and intermountain West of the United States, which will strain an already-maxed-out system as increased hospitalizations and deaths follow, say infectious diseases specialists.

“I think the situation in 2 to 4 weeks is going to be grim,” said Andrew Pavia, MD, chief of the division of pediatric infectious diseases at the University of Utah School of Medicine in Salt Lake City, on a call yesterday with reporters, sponsored by the Infectious Diseases Society of America (IDSA).

Cases began rising in Utah in mid-September and have gone up steeply since, increasing from 450 cases per day to 2,650 reported on Nov. 8, according to the Johns Hopkins Coronavirus Resource Center. The New York Times reports that the 7-day rolling average for hospitalizations have gone up 34% and deaths have risen 93%, with 11 deaths this past Tuesday.

Other states in the west – Montana, Idaho, and Wyoming, which reported 1,232 cases on Tuesday and have been averaging 660 cases a day in the last week, according to the Times – are being equally hard hit. The same is true for states in the upper Midwest, including North Dakota, South Dakota, Minnesota, Wisconsin, and Iowa.

Most of the states being hit now have large swaths of rural countryside, which means health resources are limited and spread out, said Pavia.

“The situation really has to be described as dire,” said Pavia, noting that intensive care units in Utah are full, including contingency units that were purpose-built for the pandemic. Physicians and nurses are burned out and in short supply, he said. Instead of a 1:1 or 1:2 nurse-to-ICU patient ratio, the ratio is now 1:4, said Pavia. “Throughout the region, people are facing a crisis in staffing.”

The University of Utah hospital normally takes referrals from Idaho, Wyoming, and northern Arizona, but is prioritizing Utah residents for ICU admission, said Pavia.

Both Pavia and Daniel P. McQuillen, MD, president-elect of IDSA, also noted the shortage of infectious diseases specialists, which began at least a decade ago. McQuillen, senior infectious diseases physician at Beth Israel Lahey Health in Boston, said he and colleagues had done some research earlier this year anticipating the pandemic’s spread, and found that some 80% of counties – including the rural counties in the states now being hit – have one or zero infectious disease specialists.

Those specialists can help improve patient outcomes, explained McQuillen.
 

Colleges likely driving spike

Pavia said the reasons for sharp increases in the region vary, but there are several areas of commonality. Most of the states didn’t have many cases early in the pandemic, “so perhaps there was less fear of the virus.” There were fewer actions by government officials, driven perhaps by the reluctance to take on individuals who are distrustful of government, he said.

Cases started going up after some events – such as the August motorcycle rally in Sturgis, South Dakota – but the acceleration in September was likely driven by the reopening of colleges across the region, said Pavia.

“Most of the states have kept in-person schooling, and probably more importantly, they’ve kept extracurricular activities in sports,” he said, adding that in many of the areas the weather has turned cooler, driving people indoors.

McQuillen said it has been shown that a significant amount of transmission occurs within homes – and college students may be bringing the virus home and fueling spread, in addition to people not wearing masks while at small family gatherings.

Both he and Pavia said more emphasis needs to be placed on mitigation measures such as mask-wearing as well as on testing. IDSA is starting #MaskUpAmerica, a public service campaign aimed at getting people to wear masks in all community settings, including at work, in churches, at social gatherings, in gyms, and on public transportation.

Pavia said in some places people are refusing to be tested because they don’t want to be quarantined.

Utah Gov. Gary Herbert (R) issued a statewide mask mandate this past weekend and announced some other restrictions, including a 2-week pause on most, but not all, athletic events, according to CBS News. But local pushback could weaken those measures, said Pavia.

Many people are looking to vaccines to usher in a return to normal. But, said Pavia, “vaccines aren’t going to help us out much this winter,” noting that initial doses will be given mostly to first responders and healthcare workers.

“The only way we’re going to get out of this this winter is by doing the things that we’ve been talking about for months – wearing a mask, watching your social distance, and avoiding large gatherings,” he said.

There is an end in sight, said Pavia, but it won’t be in early 2021. “That end is next summer or fall,” he said. “And that’s a hard message to give but it’s really critical.”

McQuillen agreed: “Wearing masks and distancing are exactly all we have probably until middle of next year.”
 

This article first appeared on Medscape.com.

Coronavirus infections are expected to continue to climb in the upper Midwest and intermountain West of the United States, which will strain an already-maxed-out system as increased hospitalizations and deaths follow, say infectious diseases specialists.

“I think the situation in 2 to 4 weeks is going to be grim,” said Andrew Pavia, MD, chief of the division of pediatric infectious diseases at the University of Utah School of Medicine in Salt Lake City, on a call yesterday with reporters, sponsored by the Infectious Diseases Society of America (IDSA).

Cases began rising in Utah in mid-September and have gone up steeply since, increasing from 450 cases per day to 2,650 reported on Nov. 8, according to the Johns Hopkins Coronavirus Resource Center. The New York Times reports that the 7-day rolling average for hospitalizations have gone up 34% and deaths have risen 93%, with 11 deaths this past Tuesday.

Other states in the west – Montana, Idaho, and Wyoming, which reported 1,232 cases on Tuesday and have been averaging 660 cases a day in the last week, according to the Times – are being equally hard hit. The same is true for states in the upper Midwest, including North Dakota, South Dakota, Minnesota, Wisconsin, and Iowa.

Most of the states being hit now have large swaths of rural countryside, which means health resources are limited and spread out, said Pavia.

“The situation really has to be described as dire,” said Pavia, noting that intensive care units in Utah are full, including contingency units that were purpose-built for the pandemic. Physicians and nurses are burned out and in short supply, he said. Instead of a 1:1 or 1:2 nurse-to-ICU patient ratio, the ratio is now 1:4, said Pavia. “Throughout the region, people are facing a crisis in staffing.”

The University of Utah hospital normally takes referrals from Idaho, Wyoming, and northern Arizona, but is prioritizing Utah residents for ICU admission, said Pavia.

Both Pavia and Daniel P. McQuillen, MD, president-elect of IDSA, also noted the shortage of infectious diseases specialists, which began at least a decade ago. McQuillen, senior infectious diseases physician at Beth Israel Lahey Health in Boston, said he and colleagues had done some research earlier this year anticipating the pandemic’s spread, and found that some 80% of counties – including the rural counties in the states now being hit – have one or zero infectious disease specialists.

Those specialists can help improve patient outcomes, explained McQuillen.
 

Colleges likely driving spike

Pavia said the reasons for sharp increases in the region vary, but there are several areas of commonality. Most of the states didn’t have many cases early in the pandemic, “so perhaps there was less fear of the virus.” There were fewer actions by government officials, driven perhaps by the reluctance to take on individuals who are distrustful of government, he said.

Cases started going up after some events – such as the August motorcycle rally in Sturgis, South Dakota – but the acceleration in September was likely driven by the reopening of colleges across the region, said Pavia.

“Most of the states have kept in-person schooling, and probably more importantly, they’ve kept extracurricular activities in sports,” he said, adding that in many of the areas the weather has turned cooler, driving people indoors.

McQuillen said it has been shown that a significant amount of transmission occurs within homes – and college students may be bringing the virus home and fueling spread, in addition to people not wearing masks while at small family gatherings.

Both he and Pavia said more emphasis needs to be placed on mitigation measures such as mask-wearing as well as on testing. IDSA is starting #MaskUpAmerica, a public service campaign aimed at getting people to wear masks in all community settings, including at work, in churches, at social gatherings, in gyms, and on public transportation.

Pavia said in some places people are refusing to be tested because they don’t want to be quarantined.

Utah Gov. Gary Herbert (R) issued a statewide mask mandate this past weekend and announced some other restrictions, including a 2-week pause on most, but not all, athletic events, according to CBS News. But local pushback could weaken those measures, said Pavia.

Many people are looking to vaccines to usher in a return to normal. But, said Pavia, “vaccines aren’t going to help us out much this winter,” noting that initial doses will be given mostly to first responders and healthcare workers.

“The only way we’re going to get out of this this winter is by doing the things that we’ve been talking about for months – wearing a mask, watching your social distance, and avoiding large gatherings,” he said.

There is an end in sight, said Pavia, but it won’t be in early 2021. “That end is next summer or fall,” he said. “And that’s a hard message to give but it’s really critical.”

McQuillen agreed: “Wearing masks and distancing are exactly all we have probably until middle of next year.”
 

This article first appeared on Medscape.com.

One in five COVID-19 patients are diagnosed with a psychiatric disorder such as anxiety or depression within 3 months of testing positive for the virus, new research suggests.

“People have been worried that COVID-19 survivors will be at greater risk of psychiatric disorders, and our findings in a large and detailed study show this to be true,” principal investigator Paul Harrison, BM, DM, professor of psychiatry, University of Oxford, Oxford, United Kingdom, said in a statement.

Health services “need to be ready to provide care, especially since our results are likely to be underestimates of the actual number of cases,” said Harrison.

The study also showed that having a psychiatric disorder independently increases the risk of getting COVID-19 – a finding that’s in line with research published earlier this month.

“Having a psychiatric illness should be added to the list of risk factors for COVID-19,” study coauthor Maxime Taquet, PhD, University of Oxford, said in the release.

The study was published online Nov. 9 in The Lancet Psychiatry.
 

Double the risk

The investigators took advantage of the TriNetX analytics network, which captured deidentified data from electronic health records of a total of 69.8 million patients from 54 healthcare organizations in the United States.

Of those patients, 62,354 adults were diagnosed with COVID-19 between Jan. 20 and Aug. 1, 2020.

To assess the psychiatric sequelae of COVID-19, the investigators created propensity score–matched cohorts of patients who had received a diagnosis of other conditions that represented a range of common acute presentations.

In 14 to 90 days after being diagnosed with COVID-19, 5.8% of patients received a first recorded diagnosis of psychiatric illness. Among patients with health problems other than COVID, 2.5% to 3.4% of patients received a psychiatric diagnosis, the authors report. The risk was greatest for anxiety disorders, depression, and insomnia.

Older COVID-19 patients had a two- to threefold increased risk for a first dementia diagnosis, a finding that supports an earlier UK study.

Some of this excess risk could reflect misdiagnosed cases of delirium or transient cognitive impairment due to reversible cerebral events, the authors noted.

The study also revealed a bidirectional relationship between mental illness and COVID-19. Individuals with a psychiatric diagnosis were about 65% more likely to be diagnosed with COVID-19 in comparison with their counterparts who did not have mental illness, independently of known physical health risk factors for COVID-19.

“We did not anticipate that psychiatric history would be an independent risk factor for COVID-19. This finding appears robust, being observed in all age strata and in both sexes, and was substantial,” the authors write.

At present, “we don’t understand what the explanation is for the associations between COVID and mental illness. We are looking into this in more detail to try and understand better what subgroups are particularly vulnerable in this regard,” Harrison told Medscape Medical News.
 

“Ambitious” research

Commenting on the findings for Medscape Medical News, Roy H. Perlis, MD, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, said this is “an ambitious effort to understand the short-term consequences of COVID in terms of brain diseases.”

Perlis said he’s not particularly surprised by the increase in psychiatric diagnoses among COVID-19 patients.

“After COVID infection, people are more likely to get close medical follow-up than usual. They’re more likely to be accessing the healthcare system; after all, they’ve already had COVID, so they’re probably less fearful of seeing their doctor. But, that probably also means they’re more likely to get a new diagnosis of something like depression,” he said.

Dementia may be the clearest illustration of this, Perlis said. “It seems less likely that dementia develops a month after COVID; more likely, something that happens during the illness leads someone to be more likely to diagnose dementia later on,” he noted.

Perlis cautioned against being “unnecessarily alarmed” by the findings in this study.

“We know that rates of depression in the UK and the US, as in much of the world, are substantially elevated right now. Much of this is likely a consequence of the stress and disruption that accompanies the pandemic,” said Perlis.

The study was funded by the National Institute for Health Research. Harrison has disclosed no relevant financial relationships. One author is an employee of TriNetX. Perlis has received consulting fees for service on scientific advisory boards of Belle Artificial Intelligence, Burrage Capital, Genomind, Psy Therapeutics, Outermost Therapeutics, RID Ventures, and Takeda. He holds equity in Psy Therapeutics and Outermost Therapeutics.
 

This article first appeared on Medscape.com.

One in five COVID-19 patients are diagnosed with a psychiatric disorder such as anxiety or depression within 3 months of testing positive for the virus, new research suggests.

“People have been worried that COVID-19 survivors will be at greater risk of psychiatric disorders, and our findings in a large and detailed study show this to be true,” principal investigator Paul Harrison, BM, DM, professor of psychiatry, University of Oxford, Oxford, United Kingdom, said in a statement.

Health services “need to be ready to provide care, especially since our results are likely to be underestimates of the actual number of cases,” said Harrison.

The study also showed that having a psychiatric disorder independently increases the risk of getting COVID-19 – a finding that’s in line with research published earlier this month.

“Having a psychiatric illness should be added to the list of risk factors for COVID-19,” study coauthor Maxime Taquet, PhD, University of Oxford, said in the release.

The study was published online Nov. 9 in The Lancet Psychiatry.
 

Double the risk

The investigators took advantage of the TriNetX analytics network, which captured deidentified data from electronic health records of a total of 69.8 million patients from 54 healthcare organizations in the United States.

Of those patients, 62,354 adults were diagnosed with COVID-19 between Jan. 20 and Aug. 1, 2020.

To assess the psychiatric sequelae of COVID-19, the investigators created propensity score–matched cohorts of patients who had received a diagnosis of other conditions that represented a range of common acute presentations.

In 14 to 90 days after being diagnosed with COVID-19, 5.8% of patients received a first recorded diagnosis of psychiatric illness. Among patients with health problems other than COVID, 2.5% to 3.4% of patients received a psychiatric diagnosis, the authors report. The risk was greatest for anxiety disorders, depression, and insomnia.

Older COVID-19 patients had a two- to threefold increased risk for a first dementia diagnosis, a finding that supports an earlier UK study.

Some of this excess risk could reflect misdiagnosed cases of delirium or transient cognitive impairment due to reversible cerebral events, the authors noted.

The study also revealed a bidirectional relationship between mental illness and COVID-19. Individuals with a psychiatric diagnosis were about 65% more likely to be diagnosed with COVID-19 in comparison with their counterparts who did not have mental illness, independently of known physical health risk factors for COVID-19.

“We did not anticipate that psychiatric history would be an independent risk factor for COVID-19. This finding appears robust, being observed in all age strata and in both sexes, and was substantial,” the authors write.

At present, “we don’t understand what the explanation is for the associations between COVID and mental illness. We are looking into this in more detail to try and understand better what subgroups are particularly vulnerable in this regard,” Harrison told Medscape Medical News.
 

“Ambitious” research

Commenting on the findings for Medscape Medical News, Roy H. Perlis, MD, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, said this is “an ambitious effort to understand the short-term consequences of COVID in terms of brain diseases.”

Perlis said he’s not particularly surprised by the increase in psychiatric diagnoses among COVID-19 patients.

“After COVID infection, people are more likely to get close medical follow-up than usual. They’re more likely to be accessing the healthcare system; after all, they’ve already had COVID, so they’re probably less fearful of seeing their doctor. But, that probably also means they’re more likely to get a new diagnosis of something like depression,” he said.

Dementia may be the clearest illustration of this, Perlis said. “It seems less likely that dementia develops a month after COVID; more likely, something that happens during the illness leads someone to be more likely to diagnose dementia later on,” he noted.

Perlis cautioned against being “unnecessarily alarmed” by the findings in this study.

“We know that rates of depression in the UK and the US, as in much of the world, are substantially elevated right now. Much of this is likely a consequence of the stress and disruption that accompanies the pandemic,” said Perlis.

The study was funded by the National Institute for Health Research. Harrison has disclosed no relevant financial relationships. One author is an employee of TriNetX. Perlis has received consulting fees for service on scientific advisory boards of Belle Artificial Intelligence, Burrage Capital, Genomind, Psy Therapeutics, Outermost Therapeutics, RID Ventures, and Takeda. He holds equity in Psy Therapeutics and Outermost Therapeutics.
 

This article first appeared on Medscape.com.

One in five COVID-19 patients are diagnosed with a psychiatric disorder such as anxiety or depression within 3 months of testing positive for the virus, new research suggests.

“People have been worried that COVID-19 survivors will be at greater risk of psychiatric disorders, and our findings in a large and detailed study show this to be true,” principal investigator Paul Harrison, BM, DM, professor of psychiatry, University of Oxford, Oxford, United Kingdom, said in a statement.

Health services “need to be ready to provide care, especially since our results are likely to be underestimates of the actual number of cases,” said Harrison.

The study also showed that having a psychiatric disorder independently increases the risk of getting COVID-19 – a finding that’s in line with research published earlier this month.

“Having a psychiatric illness should be added to the list of risk factors for COVID-19,” study coauthor Maxime Taquet, PhD, University of Oxford, said in the release.

The study was published online Nov. 9 in The Lancet Psychiatry.
 

Double the risk

The investigators took advantage of the TriNetX analytics network, which captured deidentified data from electronic health records of a total of 69.8 million patients from 54 healthcare organizations in the United States.

Of those patients, 62,354 adults were diagnosed with COVID-19 between Jan. 20 and Aug. 1, 2020.

To assess the psychiatric sequelae of COVID-19, the investigators created propensity score–matched cohorts of patients who had received a diagnosis of other conditions that represented a range of common acute presentations.

In 14 to 90 days after being diagnosed with COVID-19, 5.8% of patients received a first recorded diagnosis of psychiatric illness. Among patients with health problems other than COVID, 2.5% to 3.4% of patients received a psychiatric diagnosis, the authors report. The risk was greatest for anxiety disorders, depression, and insomnia.

Older COVID-19 patients had a two- to threefold increased risk for a first dementia diagnosis, a finding that supports an earlier UK study.

Some of this excess risk could reflect misdiagnosed cases of delirium or transient cognitive impairment due to reversible cerebral events, the authors noted.

The study also revealed a bidirectional relationship between mental illness and COVID-19. Individuals with a psychiatric diagnosis were about 65% more likely to be diagnosed with COVID-19 in comparison with their counterparts who did not have mental illness, independently of known physical health risk factors for COVID-19.

“We did not anticipate that psychiatric history would be an independent risk factor for COVID-19. This finding appears robust, being observed in all age strata and in both sexes, and was substantial,” the authors write.

At present, “we don’t understand what the explanation is for the associations between COVID and mental illness. We are looking into this in more detail to try and understand better what subgroups are particularly vulnerable in this regard,” Harrison told Medscape Medical News.
 

“Ambitious” research

Commenting on the findings for Medscape Medical News, Roy H. Perlis, MD, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, said this is “an ambitious effort to understand the short-term consequences of COVID in terms of brain diseases.”

Perlis said he’s not particularly surprised by the increase in psychiatric diagnoses among COVID-19 patients.

“After COVID infection, people are more likely to get close medical follow-up than usual. They’re more likely to be accessing the healthcare system; after all, they’ve already had COVID, so they’re probably less fearful of seeing their doctor. But, that probably also means they’re more likely to get a new diagnosis of something like depression,” he said.

Dementia may be the clearest illustration of this, Perlis said. “It seems less likely that dementia develops a month after COVID; more likely, something that happens during the illness leads someone to be more likely to diagnose dementia later on,” he noted.

Perlis cautioned against being “unnecessarily alarmed” by the findings in this study.

“We know that rates of depression in the UK and the US, as in much of the world, are substantially elevated right now. Much of this is likely a consequence of the stress and disruption that accompanies the pandemic,” said Perlis.

The study was funded by the National Institute for Health Research. Harrison has disclosed no relevant financial relationships. One author is an employee of TriNetX. Perlis has received consulting fees for service on scientific advisory boards of Belle Artificial Intelligence, Burrage Capital, Genomind, Psy Therapeutics, Outermost Therapeutics, RID Ventures, and Takeda. He holds equity in Psy Therapeutics and Outermost Therapeutics.
 

This article first appeared on Medscape.com.

Increasingly, clinicians are being called upon to advise athletes who have recovered from COVID-19 on when it is safe for them to return to play.

Now, they have two reports that offer more insights into the cardiotoxic effects of COVID-19 on the athletic heart.

In the first report, researchers report a high prevalence of pericardial involvement in college-student athletes who have recovered from COVID-19 and give their practical advice on how to let these athletes return to play safely.

In the second report, an expert panel of sports cardiologists provides a comprehensive guide to the appropriate imaging of athletes who may have cardiovascular complications from COVID-19.

Both are published in JACC: Cardiovascular Imaging.

“We were asked by the editors of JACC to submit this paper, and the impetus for it was the fact that there are so many athletes returning after being infected with COVID-19, we need to try and give guidance to cardiologists as to how best to evaluate these athletes,” Dermot Phelan, MD, PhD, Sanger Heart and Vascular Institute, Atrium Health, Charlotte, N.C., and lead author of the consensus statement, said in an interview.

The consensus statement acknowledges that information about the cardiovascular complications of COVID-19 continues to evolve. Meanwhile, pathologies such as myocarditis, pericarditis, and right ventricular dysfunction, in the absence of significant clinical symptoms, in athletes who have been affected by COVID-19 remain of considerable concern.

It also emphasizes the unique challenges the average cardiologist faces in distinguishing between what is normal for an athlete’s heart and what is true pathology after COVID-19 infection; details how different imaging modalities can help in screening, evaluating, and monitoring athletes with suspected cardiovascular complications of COVID-19 infection; and discusses the strengths and limitations of these modalities.

Finally, the consensus statement provides some well-needed guidance on return-to-play decision-making, for both the athlete and the clinician.
 

Athletic remodeling or covid-19 damage?

Athletes can develop certain cardiovascular characteristics because of their athletic activity, and sometimes, this can cloud the diagnostic picture.

“Is this change due to the effects of COVID-19, or is it just because this is an athlete’s heart? This was an international expert consensus, made up of sports cardiologists from all over the world who have a lot of experience in dealing with athletes,” Dr. Phelan said. “We were trying to relay the important information to the cardiologist who is not used to dealing with athletes on a day-to-day basis, as to what they might expect to find in that athlete, and what is not an expected finding and should be tested further.”

Phelan, a sports cardiologist, is familiar with what is normal for an athlete’s heart and what is pathology.

“We know that athletes, particularly long-term endurance athletes, develop changes in the heart that can affect not only the electrics but the structure of the heart, and sometimes, that overlaps with abnormalities with pathology. This can be a challenge for the nonsports cardiologist to differentiate,” he said.

Phelan and his group have written two other consensus documents on the management of cardiovascular problems that develop in some athletes who have been infected with COVID-19.

The first was published in May in JAMA Cardiology, and the second, which revised some of the original recommendations made in the first document, was published online Oct. 26 in JAMA Cardiology.

The first set of recommendations called for imaging studies to be done in all athletes, but the second set states that athletes who recover and are asymptomatic do not need extensive (and expensive) imaging tests.

“These two papers work hand in hand,” Dr. Phelan said. “In May, we had very little experience with COVID, and there was a lot of concern about hospitalized patients having a very high incidence of heart disease. We published those recommendations, but we recognized at the time that we had very little data and that we would reconsider once we had more experience with data.

“This current set of recommendations that we have put forth here are for those athletes who do need to get further testing, so it’s a step beyond,” Dr. Phelan added. “So the second iteration states that young athletes who had mild or no symptoms didn’t need to go through all of that cardiac testing, but others do need it.”

To do widespread cardiovascular imaging for many individuals would be very costly. Realistically, there are not that many centers in the United States that have all the sophisticated equipment required to do such testing, Dr. Phelan noted.

“One of our major points is difficulty obtaining the test, but also the cost; these are very expensive tests. There are limitations. They are useful when used in the correct context,” he said.
 

To play or not to play, that is the question

Partho P. Sengupta, MD, DM, had to answer that question for more than 50 young athletes who were returning to college at West Virginia University, anxious to be back with their teams and on the playing field. They had been infected with COVID-19 and needed to know when they could return to play.

Dr. Sengupta, who is also an author for the Phelan et al consensus statement on imaging, said there was a lot of pressure – from all the various stakeholders, and from anxious parents, worried college athletes, their teammates, and the university – to determine if the youngsters could return to play.

The fear was that COVID-19 infection left the young athlete’s heart vulnerable to myocarditis and, thus, sudden death on the playing field after strenuous activity.

“At the time we were doing this imaging, there was a lot of concern in the media, and papers were coming out reporting a lot of cardiac involvement or myocarditis associated with COVID-19. Nobody really knew what to do,” he explained.

“There were all kinds of questions, concerns. The parents were putting pressure on us, the athletes wanted to know, the teams, the university. So we put together a team and completed all of the examinations, including testing of blood markers, within a 2-week period. These young athletes, they’re scared, they’re worried and anxious, they don’t know what’s going to happen with their scholarship, so there was some urgency to this work,” Dr. Sengupta said.

“We had to screen all comers within a very short period. We had 54 consecutive patients, gave them full screening, full battery of tests, blood tests, all in a 2-week period,” he said.

Speed was of the essence, and Dr. Sengupta and his team rolled up their sleeves and got to work “We had to know who was safe to clear to return to play and who might need extra follow-up.”
 

Screening echocardiograms

They performed screening echocardiograms on 54 consecutive college athletes who had tested positive for COVID-19 on reverse transcription polymerase chain reaction nasal swab testing or who showed that they had IgG antibodies against COVID-19. The screening echocardiograms were done after the athletes had quarantined for at least 14 days and were no longer infectious.

Most (85%) were male, and the mean age was 19 years. A total of 16 (30%) athletes were asymptomatic, 36 (66%) reported mild COVID-19 related symptoms, and two (4%) reported moderate symptoms.

Of the 54 athletes who were initially screened with echocardiography, 48 (11 asymptomatic, 37 symptomatic), went on to have cardiac magnetic resonance imaging.

Results showed that more than half the athletes (27; 56.3%), showed some cardiac abnormality. The most common was pericardial late enhancement with associated pericardial effusion, affecting 19 (39.5%) athletes.

Of these, six (12.5%) had reduced global longitudinal strain (GLS) or an increased native T1.

One patient showed myocardial enhancement.

Additionally, seven athletes (14.6%) had reduced left ventricular ejection fraction or reduced GLS with or without increased native T1. Native T2 levels were normal in all subjects and no specific imaging features of myocardial inflammation were identified.

Participants were brought back to receive the results of their tests and to get an individualized plan about their safe return to play 3 to 5 weeks after they had ceased to be infectious with COVID-19.

“We saw pericardial inflammation that was resolving. We did not see any blood biomarkers to suggest that there was active inflammation going on,” he said. “We also did not see any muscle inflammation, but we did see pockets of fluid in over a third of our athletes.”

Fortunately, most were deemed able to get back to playing safely, despite having evidence of pericardial inflammation.

This was on strict condition that they be monitored very closely for any adverse events that might occur as they began to exercise again.

“Once they go back to the field to start exercising and practicing, it is under great supervision. We instructed all of our sports physicians and other team managers that these people need to be observed very carefully. So as long as they were asymptomatic, even though the signs of pericardial inflammation were there, if there were no signs of inflammation in the blood, we let them go back to play, closely monitored,” Dr. Sengupta said.

A small number remained very symptomatic at the end of the 5 weeks and were referred to cardiac rehabilitation, Dr. Sengupta said. “They were tired, fatigued, short of breath, even 5 weeks after they got over COVID, so we sent them for cardiac rehab to help them get conditioned again.”

The researchers plan to reevaluate and reimage all of the athletes in another 3 months to monitor their cardiac health.

Dr. Sengupta acknowledged the limitations of this single-center, nonrandomized, controlled report, but insists reports such as this add a bit more to what we are learning about COVID-19 every day.

“These kids were coming to us and asking questions. You have to use the best science you have available to you at that point in time. Some people ask why we did not have a control group, but how do you design a control population in the midst of a pandemic? The science may or may not be perfect, I agree, but the information we obtained is important,” he said.

“Right now, I don’t think we have enough science, and we are still learning. It is very difficult to predict who will develop the heart muscle disease or the pericardial disease,” Dr. Sengupta said. “We had to do our work quickly to give answers to the young athletes, their parents, their teammates, their university, as soon as possible, and we were doing this under pandemic conditions.”

The work was supported by the National Science Foundation National Institute of General Medical Sciences of the National Institutes of Health. Dr. Phelan reported no relevant financial relationships. Dr. Sengupta reported that he is a consultant for HeartSciences, Kencor Health, and Ultromics.

This article first appeared on Medscape.com.

Increasingly, clinicians are being called upon to advise athletes who have recovered from COVID-19 on when it is safe for them to return to play.

Now, they have two reports that offer more insights into the cardiotoxic effects of COVID-19 on the athletic heart.

In the first report, researchers report a high prevalence of pericardial involvement in college-student athletes who have recovered from COVID-19 and give their practical advice on how to let these athletes return to play safely.

In the second report, an expert panel of sports cardiologists provides a comprehensive guide to the appropriate imaging of athletes who may have cardiovascular complications from COVID-19.

Both are published in JACC: Cardiovascular Imaging.

“We were asked by the editors of JACC to submit this paper, and the impetus for it was the fact that there are so many athletes returning after being infected with COVID-19, we need to try and give guidance to cardiologists as to how best to evaluate these athletes,” Dermot Phelan, MD, PhD, Sanger Heart and Vascular Institute, Atrium Health, Charlotte, N.C., and lead author of the consensus statement, said in an interview.

The consensus statement acknowledges that information about the cardiovascular complications of COVID-19 continues to evolve. Meanwhile, pathologies such as myocarditis, pericarditis, and right ventricular dysfunction, in the absence of significant clinical symptoms, in athletes who have been affected by COVID-19 remain of considerable concern.

It also emphasizes the unique challenges the average cardiologist faces in distinguishing between what is normal for an athlete’s heart and what is true pathology after COVID-19 infection; details how different imaging modalities can help in screening, evaluating, and monitoring athletes with suspected cardiovascular complications of COVID-19 infection; and discusses the strengths and limitations of these modalities.

Finally, the consensus statement provides some well-needed guidance on return-to-play decision-making, for both the athlete and the clinician.
 

Athletic remodeling or covid-19 damage?

Athletes can develop certain cardiovascular characteristics because of their athletic activity, and sometimes, this can cloud the diagnostic picture.

“Is this change due to the effects of COVID-19, or is it just because this is an athlete’s heart? This was an international expert consensus, made up of sports cardiologists from all over the world who have a lot of experience in dealing with athletes,” Dr. Phelan said. “We were trying to relay the important information to the cardiologist who is not used to dealing with athletes on a day-to-day basis, as to what they might expect to find in that athlete, and what is not an expected finding and should be tested further.”

Phelan, a sports cardiologist, is familiar with what is normal for an athlete’s heart and what is pathology.

“We know that athletes, particularly long-term endurance athletes, develop changes in the heart that can affect not only the electrics but the structure of the heart, and sometimes, that overlaps with abnormalities with pathology. This can be a challenge for the nonsports cardiologist to differentiate,” he said.

Phelan and his group have written two other consensus documents on the management of cardiovascular problems that develop in some athletes who have been infected with COVID-19.

The first was published in May in JAMA Cardiology, and the second, which revised some of the original recommendations made in the first document, was published online Oct. 26 in JAMA Cardiology.

The first set of recommendations called for imaging studies to be done in all athletes, but the second set states that athletes who recover and are asymptomatic do not need extensive (and expensive) imaging tests.

“These two papers work hand in hand,” Dr. Phelan said. “In May, we had very little experience with COVID, and there was a lot of concern about hospitalized patients having a very high incidence of heart disease. We published those recommendations, but we recognized at the time that we had very little data and that we would reconsider once we had more experience with data.

“This current set of recommendations that we have put forth here are for those athletes who do need to get further testing, so it’s a step beyond,” Dr. Phelan added. “So the second iteration states that young athletes who had mild or no symptoms didn’t need to go through all of that cardiac testing, but others do need it.”

To do widespread cardiovascular imaging for many individuals would be very costly. Realistically, there are not that many centers in the United States that have all the sophisticated equipment required to do such testing, Dr. Phelan noted.

“One of our major points is difficulty obtaining the test, but also the cost; these are very expensive tests. There are limitations. They are useful when used in the correct context,” he said.
 

To play or not to play, that is the question

Partho P. Sengupta, MD, DM, had to answer that question for more than 50 young athletes who were returning to college at West Virginia University, anxious to be back with their teams and on the playing field. They had been infected with COVID-19 and needed to know when they could return to play.

Dr. Sengupta, who is also an author for the Phelan et al consensus statement on imaging, said there was a lot of pressure – from all the various stakeholders, and from anxious parents, worried college athletes, their teammates, and the university – to determine if the youngsters could return to play.

The fear was that COVID-19 infection left the young athlete’s heart vulnerable to myocarditis and, thus, sudden death on the playing field after strenuous activity.

“At the time we were doing this imaging, there was a lot of concern in the media, and papers were coming out reporting a lot of cardiac involvement or myocarditis associated with COVID-19. Nobody really knew what to do,” he explained.

“There were all kinds of questions, concerns. The parents were putting pressure on us, the athletes wanted to know, the teams, the university. So we put together a team and completed all of the examinations, including testing of blood markers, within a 2-week period. These young athletes, they’re scared, they’re worried and anxious, they don’t know what’s going to happen with their scholarship, so there was some urgency to this work,” Dr. Sengupta said.

“We had to screen all comers within a very short period. We had 54 consecutive patients, gave them full screening, full battery of tests, blood tests, all in a 2-week period,” he said.

Speed was of the essence, and Dr. Sengupta and his team rolled up their sleeves and got to work “We had to know who was safe to clear to return to play and who might need extra follow-up.”
 

Screening echocardiograms

They performed screening echocardiograms on 54 consecutive college athletes who had tested positive for COVID-19 on reverse transcription polymerase chain reaction nasal swab testing or who showed that they had IgG antibodies against COVID-19. The screening echocardiograms were done after the athletes had quarantined for at least 14 days and were no longer infectious.

Most (85%) were male, and the mean age was 19 years. A total of 16 (30%) athletes were asymptomatic, 36 (66%) reported mild COVID-19 related symptoms, and two (4%) reported moderate symptoms.

Of the 54 athletes who were initially screened with echocardiography, 48 (11 asymptomatic, 37 symptomatic), went on to have cardiac magnetic resonance imaging.

Results showed that more than half the athletes (27; 56.3%), showed some cardiac abnormality. The most common was pericardial late enhancement with associated pericardial effusion, affecting 19 (39.5%) athletes.

Of these, six (12.5%) had reduced global longitudinal strain (GLS) or an increased native T1.

One patient showed myocardial enhancement.

Additionally, seven athletes (14.6%) had reduced left ventricular ejection fraction or reduced GLS with or without increased native T1. Native T2 levels were normal in all subjects and no specific imaging features of myocardial inflammation were identified.

Participants were brought back to receive the results of their tests and to get an individualized plan about their safe return to play 3 to 5 weeks after they had ceased to be infectious with COVID-19.

“We saw pericardial inflammation that was resolving. We did not see any blood biomarkers to suggest that there was active inflammation going on,” he said. “We also did not see any muscle inflammation, but we did see pockets of fluid in over a third of our athletes.”

Fortunately, most were deemed able to get back to playing safely, despite having evidence of pericardial inflammation.

This was on strict condition that they be monitored very closely for any adverse events that might occur as they began to exercise again.

“Once they go back to the field to start exercising and practicing, it is under great supervision. We instructed all of our sports physicians and other team managers that these people need to be observed very carefully. So as long as they were asymptomatic, even though the signs of pericardial inflammation were there, if there were no signs of inflammation in the blood, we let them go back to play, closely monitored,” Dr. Sengupta said.

A small number remained very symptomatic at the end of the 5 weeks and were referred to cardiac rehabilitation, Dr. Sengupta said. “They were tired, fatigued, short of breath, even 5 weeks after they got over COVID, so we sent them for cardiac rehab to help them get conditioned again.”

The researchers plan to reevaluate and reimage all of the athletes in another 3 months to monitor their cardiac health.

Dr. Sengupta acknowledged the limitations of this single-center, nonrandomized, controlled report, but insists reports such as this add a bit more to what we are learning about COVID-19 every day.

“These kids were coming to us and asking questions. You have to use the best science you have available to you at that point in time. Some people ask why we did not have a control group, but how do you design a control population in the midst of a pandemic? The science may or may not be perfect, I agree, but the information we obtained is important,” he said.

“Right now, I don’t think we have enough science, and we are still learning. It is very difficult to predict who will develop the heart muscle disease or the pericardial disease,” Dr. Sengupta said. “We had to do our work quickly to give answers to the young athletes, their parents, their teammates, their university, as soon as possible, and we were doing this under pandemic conditions.”

The work was supported by the National Science Foundation National Institute of General Medical Sciences of the National Institutes of Health. Dr. Phelan reported no relevant financial relationships. Dr. Sengupta reported that he is a consultant for HeartSciences, Kencor Health, and Ultromics.

This article first appeared on Medscape.com.

Increasingly, clinicians are being called upon to advise athletes who have recovered from COVID-19 on when it is safe for them to return to play.

Now, they have two reports that offer more insights into the cardiotoxic effects of COVID-19 on the athletic heart.

In the first report, researchers report a high prevalence of pericardial involvement in college-student athletes who have recovered from COVID-19 and give their practical advice on how to let these athletes return to play safely.

In the second report, an expert panel of sports cardiologists provides a comprehensive guide to the appropriate imaging of athletes who may have cardiovascular complications from COVID-19.

Both are published in JACC: Cardiovascular Imaging.

“We were asked by the editors of JACC to submit this paper, and the impetus for it was the fact that there are so many athletes returning after being infected with COVID-19, we need to try and give guidance to cardiologists as to how best to evaluate these athletes,” Dermot Phelan, MD, PhD, Sanger Heart and Vascular Institute, Atrium Health, Charlotte, N.C., and lead author of the consensus statement, said in an interview.

The consensus statement acknowledges that information about the cardiovascular complications of COVID-19 continues to evolve. Meanwhile, pathologies such as myocarditis, pericarditis, and right ventricular dysfunction, in the absence of significant clinical symptoms, in athletes who have been affected by COVID-19 remain of considerable concern.

It also emphasizes the unique challenges the average cardiologist faces in distinguishing between what is normal for an athlete’s heart and what is true pathology after COVID-19 infection; details how different imaging modalities can help in screening, evaluating, and monitoring athletes with suspected cardiovascular complications of COVID-19 infection; and discusses the strengths and limitations of these modalities.

Finally, the consensus statement provides some well-needed guidance on return-to-play decision-making, for both the athlete and the clinician.
 

Athletic remodeling or covid-19 damage?

Athletes can develop certain cardiovascular characteristics because of their athletic activity, and sometimes, this can cloud the diagnostic picture.

“Is this change due to the effects of COVID-19, or is it just because this is an athlete’s heart? This was an international expert consensus, made up of sports cardiologists from all over the world who have a lot of experience in dealing with athletes,” Dr. Phelan said. “We were trying to relay the important information to the cardiologist who is not used to dealing with athletes on a day-to-day basis, as to what they might expect to find in that athlete, and what is not an expected finding and should be tested further.”

Phelan, a sports cardiologist, is familiar with what is normal for an athlete’s heart and what is pathology.

“We know that athletes, particularly long-term endurance athletes, develop changes in the heart that can affect not only the electrics but the structure of the heart, and sometimes, that overlaps with abnormalities with pathology. This can be a challenge for the nonsports cardiologist to differentiate,” he said.

Phelan and his group have written two other consensus documents on the management of cardiovascular problems that develop in some athletes who have been infected with COVID-19.

The first was published in May in JAMA Cardiology, and the second, which revised some of the original recommendations made in the first document, was published online Oct. 26 in JAMA Cardiology.

The first set of recommendations called for imaging studies to be done in all athletes, but the second set states that athletes who recover and are asymptomatic do not need extensive (and expensive) imaging tests.

“These two papers work hand in hand,” Dr. Phelan said. “In May, we had very little experience with COVID, and there was a lot of concern about hospitalized patients having a very high incidence of heart disease. We published those recommendations, but we recognized at the time that we had very little data and that we would reconsider once we had more experience with data.

“This current set of recommendations that we have put forth here are for those athletes who do need to get further testing, so it’s a step beyond,” Dr. Phelan added. “So the second iteration states that young athletes who had mild or no symptoms didn’t need to go through all of that cardiac testing, but others do need it.”

To do widespread cardiovascular imaging for many individuals would be very costly. Realistically, there are not that many centers in the United States that have all the sophisticated equipment required to do such testing, Dr. Phelan noted.

“One of our major points is difficulty obtaining the test, but also the cost; these are very expensive tests. There are limitations. They are useful when used in the correct context,” he said.
 

To play or not to play, that is the question

Partho P. Sengupta, MD, DM, had to answer that question for more than 50 young athletes who were returning to college at West Virginia University, anxious to be back with their teams and on the playing field. They had been infected with COVID-19 and needed to know when they could return to play.

Dr. Sengupta, who is also an author for the Phelan et al consensus statement on imaging, said there was a lot of pressure – from all the various stakeholders, and from anxious parents, worried college athletes, their teammates, and the university – to determine if the youngsters could return to play.

The fear was that COVID-19 infection left the young athlete’s heart vulnerable to myocarditis and, thus, sudden death on the playing field after strenuous activity.

“At the time we were doing this imaging, there was a lot of concern in the media, and papers were coming out reporting a lot of cardiac involvement or myocarditis associated with COVID-19. Nobody really knew what to do,” he explained.

“There were all kinds of questions, concerns. The parents were putting pressure on us, the athletes wanted to know, the teams, the university. So we put together a team and completed all of the examinations, including testing of blood markers, within a 2-week period. These young athletes, they’re scared, they’re worried and anxious, they don’t know what’s going to happen with their scholarship, so there was some urgency to this work,” Dr. Sengupta said.

“We had to screen all comers within a very short period. We had 54 consecutive patients, gave them full screening, full battery of tests, blood tests, all in a 2-week period,” he said.

Speed was of the essence, and Dr. Sengupta and his team rolled up their sleeves and got to work “We had to know who was safe to clear to return to play and who might need extra follow-up.”
 

Screening echocardiograms

They performed screening echocardiograms on 54 consecutive college athletes who had tested positive for COVID-19 on reverse transcription polymerase chain reaction nasal swab testing or who showed that they had IgG antibodies against COVID-19. The screening echocardiograms were done after the athletes had quarantined for at least 14 days and were no longer infectious.

Most (85%) were male, and the mean age was 19 years. A total of 16 (30%) athletes were asymptomatic, 36 (66%) reported mild COVID-19 related symptoms, and two (4%) reported moderate symptoms.

Of the 54 athletes who were initially screened with echocardiography, 48 (11 asymptomatic, 37 symptomatic), went on to have cardiac magnetic resonance imaging.

Results showed that more than half the athletes (27; 56.3%), showed some cardiac abnormality. The most common was pericardial late enhancement with associated pericardial effusion, affecting 19 (39.5%) athletes.

Of these, six (12.5%) had reduced global longitudinal strain (GLS) or an increased native T1.

One patient showed myocardial enhancement.

Additionally, seven athletes (14.6%) had reduced left ventricular ejection fraction or reduced GLS with or without increased native T1. Native T2 levels were normal in all subjects and no specific imaging features of myocardial inflammation were identified.

Participants were brought back to receive the results of their tests and to get an individualized plan about their safe return to play 3 to 5 weeks after they had ceased to be infectious with COVID-19.

“We saw pericardial inflammation that was resolving. We did not see any blood biomarkers to suggest that there was active inflammation going on,” he said. “We also did not see any muscle inflammation, but we did see pockets of fluid in over a third of our athletes.”

Fortunately, most were deemed able to get back to playing safely, despite having evidence of pericardial inflammation.

This was on strict condition that they be monitored very closely for any adverse events that might occur as they began to exercise again.

“Once they go back to the field to start exercising and practicing, it is under great supervision. We instructed all of our sports physicians and other team managers that these people need to be observed very carefully. So as long as they were asymptomatic, even though the signs of pericardial inflammation were there, if there were no signs of inflammation in the blood, we let them go back to play, closely monitored,” Dr. Sengupta said.

A small number remained very symptomatic at the end of the 5 weeks and were referred to cardiac rehabilitation, Dr. Sengupta said. “They were tired, fatigued, short of breath, even 5 weeks after they got over COVID, so we sent them for cardiac rehab to help them get conditioned again.”

The researchers plan to reevaluate and reimage all of the athletes in another 3 months to monitor their cardiac health.

Dr. Sengupta acknowledged the limitations of this single-center, nonrandomized, controlled report, but insists reports such as this add a bit more to what we are learning about COVID-19 every day.

“These kids were coming to us and asking questions. You have to use the best science you have available to you at that point in time. Some people ask why we did not have a control group, but how do you design a control population in the midst of a pandemic? The science may or may not be perfect, I agree, but the information we obtained is important,” he said.

“Right now, I don’t think we have enough science, and we are still learning. It is very difficult to predict who will develop the heart muscle disease or the pericardial disease,” Dr. Sengupta said. “We had to do our work quickly to give answers to the young athletes, their parents, their teammates, their university, as soon as possible, and we were doing this under pandemic conditions.”

The work was supported by the National Science Foundation National Institute of General Medical Sciences of the National Institutes of Health. Dr. Phelan reported no relevant financial relationships. Dr. Sengupta reported that he is a consultant for HeartSciences, Kencor Health, and Ultromics.

This article first appeared on Medscape.com.