MDedge Endocrinology

A French population-based study provides further evidence that the BNT162b2 Pfizer-BioNTech mRNA COVID-19 vaccine does not increase the short-term risk for serious cardiovascular adverse events in older people.

The study showed no increased risk of myocardial infarction (MI), stroke, or pulmonary embolism (PE) following vaccination in adults aged 75 years or older in the 14 days following vaccination.

“These findings regarding the BNT162b2 vaccine’s short-term cardiovascular safety profile in older people are reassuring. They should be taken into account by doctors when considering implementing a third dose of the vaccine in older people,” Marie Joelle Jabagi, PharmD, PhD, with the French National Agency for Medicines and Health Products Safety, Saint-Denis, France, said in an interview.

Ridofranz/Getty Images

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

A French population-based study provides further evidence that the BNT162b2 Pfizer-BioNTech mRNA COVID-19 vaccine does not increase the short-term risk for serious cardiovascular adverse events in older people.

The study showed no increased risk of myocardial infarction (MI), stroke, or pulmonary embolism (PE) following vaccination in adults aged 75 years or older in the 14 days following vaccination.

“These findings regarding the BNT162b2 vaccine’s short-term cardiovascular safety profile in older people are reassuring. They should be taken into account by doctors when considering implementing a third dose of the vaccine in older people,” Marie Joelle Jabagi, PharmD, PhD, with the French National Agency for Medicines and Health Products Safety, Saint-Denis, France, said in an interview.

Ridofranz/Getty Images

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

A French population-based study provides further evidence that the BNT162b2 Pfizer-BioNTech mRNA COVID-19 vaccine does not increase the short-term risk for serious cardiovascular adverse events in older people.

The study showed no increased risk of myocardial infarction (MI), stroke, or pulmonary embolism (PE) following vaccination in adults aged 75 years or older in the 14 days following vaccination.

“These findings regarding the BNT162b2 vaccine’s short-term cardiovascular safety profile in older people are reassuring. They should be taken into account by doctors when considering implementing a third dose of the vaccine in older people,” Marie Joelle Jabagi, PharmD, PhD, with the French National Agency for Medicines and Health Products Safety, Saint-Denis, France, said in an interview.

Ridofranz/Getty Images

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

A new lipid-lowering agent in a class that had been written off by many is being developed by a group of academic experts, with new data showing large LDL reductions on top of high-intensity statins.

Obicetrapib is a member of the cholesteryl ester transfer protein (CETP) inhibitor class, which had fallen out of favor after several disappointments with previous drugs in this class.

These agents were initially developed for their ability to raise HDL cholesterol, which was thought to be beneficial. But that approach has now been virtually abandoned after several studies failed to show a link between raising HDL and a reduction in subsequent cardiovascular events.

However, obicetrapib, which is said to be the most potent CETP inhibitor to date, has been shown to produce impressive LDL reductions, and it’s this important data that has caused several lipid experts to want to continue its development.

New data, presented at the recent American Heart Association scientific sessions, show that obicetrapib reduces LDL by 50% when given in addition to high-intensity statins, which could place it as competition for PCSK9 inhibitors or the new agent, inclisiran, but with the advantage of oral dosing.

The drug was in development by Amgen, but the company decided to discontinue its development in 2017 after disappointing results had been seen with several other CETP inhibitors and interest in this class of agent was waning.

But academic experts in the lipid field, led by John Kastelein, MD, PhD, professor of medicine at the Academic Medical Center, University of Amsterdam, and Michael Davidson, MD, clinical professor of medicine at University of Chicago, believed the drug had potential and have acquired obicetrapib from Amgen.

Dr. Kastelein and Dr. Davidson have set up a new company – New Amsterdam Pharma – to further develop obicetrapib, and have raised $200 million from venture capital funding to complete phase 2 and phase 3 studies.

The company has a heavyweight academic advisory board including Stephen Nicholls, MD, Monash University, Clayton, Australia; Kausik Ray, MD, Imperial College London; and Christie Ballantyne, MD, Baylor College of Medicine, Houston.

“We wanted to develop obicetrapib further because of its amazing LDL-lowering properties,” Dr. Kastelein said in an interview.

“No one has paid much attention to CETP inhibitors after the HDL hypothesis was disregarded, as everyone thought these drugs were just about raising HDL. But actually, they can also lower LDL, and this particular agent reduces LDL very effectively,” Dr. Kastelein said.
 

ROSE study

Dr. Nicholls presented the latest data on obicetrapib at the AHA meeting.

“Despite the use of high-intensity statins, two-thirds of patients do not reach their target LDL level, so we have a need for new therapies that lower LDL and can be used in combination with high-intensity statins,” he explained.

He noted that earlier studies with obicetrapib showed a 45% lowering of LDL with monotherapy.

Dr. Nicholls reported that recent evidence has emerged that increases interest in inhibiting CETP to be potentially cardioprotective.

To begin, genetic studies have shown that genetic polymorphisms associated with lower levels of CETP appear to be cardioprotective, and this is associated with lower levels of LDL rather than higher levels of HDL. 

Furthermore, the REVEAL cardiovascular outcomes trial with anacetrapib (also a CETP inhibitor) in 2017 showed a significant 9% reduction in major adverse cardiac events (MACE) after 4 years of follow-up. “This was exactly predicted by the 11 mg/dL drop in absolute LDL cholesterol level. It was not predicted or associated with the increase in HDL level observed with that agent,” Dr. Nicholls said.

The objective of the current ROSE study was to evaluate the lipid-lowering ability, safety, and tolerability of obicetrapib in patients on high-intensity statins.

The study included 120 patients who had been treated on a stable dose of high-intensity statins (atorvastatin at a dose of at least 40 mg daily or rosuvastatin at a dose of 20 mg daily) for at least 8 weeks. All patients were required to have a fasting LDL of at least 70 mg/dL and the median baseline LDL was 90 mg/dL. They were randomly assigned to obicetrapib (5 mg or 10 mg daily) or placebo.

The primary endpoint was the difference between groups in percentage change in LDL from baseline to week 8, with LDL levels measured by two different techniques.

Results showed a “robust” 51% reduction in LDL with the 10-mg dose of obicetrapib, and a 42% reduction with the 5-mg dose, Dr. Nicholls reported.

These effects were comparable regardless of baseline LDL and were similar with both methods of LDL measurement. 

Almost all patients demonstrated some degree of LDL cholesterol lowering, with only three patients on the 5-mg dose and one patient on the 10-mg dose not showing any reduction in LDL.

Other results showed a dose-dependent lowering of Apo B of up to 30%, and a reduction of non-HDL cholesterol of up to 44%.

“Predictably, there were also increases of HDL cholesterol,” Dr. Nicholls said. “At the 10-mg dose, we see a 165% increase in HDL levels. That is associated with a 48% increase in Apo A1 levels. This is very consistent with findings from the previous monotherapy study.”  

There was a 56% reduction in Lp(a) levels, and a modest 11% reduction in triglycerides.

Both doses of obicetrapib were well tolerated, with no increase in the rate of adverse events. Only one patient discontinued the study drug because of an adverse event and that patient was in the placebo group, Dr. Nicholls noted.  

“Blood pressure is an important adverse event to look at in the CETP class given the challenges seen with the first CETP evaluated – torcetrapib,” Dr. Nicholls said. “But in the three clinical trials with obicetrapib conducted to date, reassuringly, we see no increase in either systolic or diastolic blood pressure with either the 5-mg or 10-mg dose.”

He concluded that obicetrapib “could be a valuable addition to high-risk patients with atherosclerotic cardiovascular disease who do not achieve their target LDL level despite use of high-intensity statin therapy.”
 

Differences from other CETP inhibitors

Asked how obicetrapib differs from other agents in the CETP inhibitor class, Dr. Nicholls replied that obicetrapib is much more potent, as shown by the large lipid changes seen with very small quantities of this drug, 5 mg or 10 mg, whereas prior CETP inhibitors showed smaller changes with much higher doses.

“We are giving very small amounts of obicetrapib and seeing very robust effects on both atherogenic and lipid parameters,” he said.  

“The other major point with this class of agent is that the first drug, torcetrapib, had toxicity, which resulted in increased cardiovascular events. But it has now been established that torcetrapib had a number of off-target effects that have not been seen with subsequent agents in this class,” he said.

Studies so far show that obicetrapib does not have torcetrapib-like effects. “That is encouraging. This, and the impressive LDL lowering effects, certainly lay the foundation for larger studies moving forward,” he added.

“This has been an intriguing field to many of us involved from the start. We started with a very disappointing result with torcetrapib. Then a couple of studies looked to be clinically futile, but we were encouraged by the REVEAL study which suggested that there might be benefit,” Dr. Nicholls said.

“If we combined the REVEAL results with the genetic data, it has actually flipped the whole CETP story upside down. We started thinking that inhibiting CETP was all about raising HDL, but it turns out that it is about LDL lowering,” he said. “And that is not only important in terms of the lipid effects but also the trials and the way they are designed.

“I think you’ll find that the future trials in this class and with this agent will have LDL very much in mind and that will very much influence the study design,” he said, adding that a larger cardiovascular outcome trial is now being planned. 

“The regulatory perspective is that LDL is a pretty trusted surrogate ... but I think an outcomes trial will be important to reinforce and reassure on safety and outline cost-effectiveness, which will help us understand where the sweet spot for using this agent in the clinic will be,” Dr. Nicholls noted.  

Dr. Kastelein explained that it has taken some time to realize that CETP inhibitors may be valuable for reducing LDL.   

“The first agent, torcetrapib, had an off-target toxicity that led to increased blood pressure but a specific part of the torcetrapib molecule was subsequently identified that was responsible for that, and subsequent agents in the CETP inhibitor class did not have such adverse effects,” he said.  

“The next agent, dalcetrapib (Roche), raised HDL but didn’t move LDL, and an outcomes trial with evacetrapib (Lilly) was stopped after 2 years because of futility, but we now believe that lipid lowering trials need longer term follow-up – up to 5 years – to see a benefit,” he noted.  

Dr. Kastelein reports that anacetrapib (Merck) has been the most powerful CETP inhibitor until now, giving an LDL reduction of about 20%, which was associated with a 10% reduction in cardiovascular events in first 4 years of follow-up. 

“Oxford academic researchers decided to continue follow-up in this trial without Merck and showed a 20% reduction in cardiovascular events by 6 years. This has been the strongest rationale for our investors,” Dr. Kastelein said.   

He pointed out that obicetrapib is much more potent than anacetrapib. “Obicetrapib reduces LDL by 50% at just a 10-mg dose, whereas anacetrapib was used at a dose of 100 mg to give a 17%-20% LDL reduction.”
 

Could HDL increase be beneficial after all?

Although increasing HDL is currently not thought to bring about a direct reduction in cardiovascular events, there is new evidence emerging that increasing HDL may confer some benefit in protecting against the development of type 2 diabetes, Dr. Kastelein noted.

“We know that statins can increase risk of developing type 2 diabetes, and post hoc analyses of previous trials with CETP inhibitors suggest that these drugs have the opposite effect,” he said. “We will investigate this protectively in our phase 3 outcomes trial. If this is a true effect, it should eventually translate into a reduction in cardiovascular outcomes, but this could take a longer time to see than the benefits of lowering LDL.”

Commenting on the current data, Steven Nissen, MD, of Cleveland Clinic, said: “The results are truly impressive – a nearly 50% LDL reduction on a background of statins with a once-daily oral agent. While PCSK9 inhibitors can achieve similar results, they are injectable and costly.

“Since anacetrapib, a much weaker CETP inhibitor, was successful at reducing major adverse cardiac events, the likelihood that obicetrapib would reduce MACE even more substantially is very high,” he added.

Dr. Nissen said he has been aware of this drug for some time and has advised the company about development options and regulatory strategy. “I have encouraged this company to develop this very promising drug,” he said.

The current study was funded by New Amsterdam Pharma. Dr. Nicholls reports grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, Infraredx, Roche, Sanofi-Regeneron and LipoScience, and honoraria from New Amsterdam Pharma, AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Kastelein is chief scientific officer of New Amsterdam Pharma.  

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

A new lipid-lowering agent in a class that had been written off by many is being developed by a group of academic experts, with new data showing large LDL reductions on top of high-intensity statins.

Obicetrapib is a member of the cholesteryl ester transfer protein (CETP) inhibitor class, which had fallen out of favor after several disappointments with previous drugs in this class.

These agents were initially developed for their ability to raise HDL cholesterol, which was thought to be beneficial. But that approach has now been virtually abandoned after several studies failed to show a link between raising HDL and a reduction in subsequent cardiovascular events.

However, obicetrapib, which is said to be the most potent CETP inhibitor to date, has been shown to produce impressive LDL reductions, and it’s this important data that has caused several lipid experts to want to continue its development.

New data, presented at the recent American Heart Association scientific sessions, show that obicetrapib reduces LDL by 50% when given in addition to high-intensity statins, which could place it as competition for PCSK9 inhibitors or the new agent, inclisiran, but with the advantage of oral dosing.

The drug was in development by Amgen, but the company decided to discontinue its development in 2017 after disappointing results had been seen with several other CETP inhibitors and interest in this class of agent was waning.

But academic experts in the lipid field, led by John Kastelein, MD, PhD, professor of medicine at the Academic Medical Center, University of Amsterdam, and Michael Davidson, MD, clinical professor of medicine at University of Chicago, believed the drug had potential and have acquired obicetrapib from Amgen.

Dr. Kastelein and Dr. Davidson have set up a new company – New Amsterdam Pharma – to further develop obicetrapib, and have raised $200 million from venture capital funding to complete phase 2 and phase 3 studies.

The company has a heavyweight academic advisory board including Stephen Nicholls, MD, Monash University, Clayton, Australia; Kausik Ray, MD, Imperial College London; and Christie Ballantyne, MD, Baylor College of Medicine, Houston.

“We wanted to develop obicetrapib further because of its amazing LDL-lowering properties,” Dr. Kastelein said in an interview.

“No one has paid much attention to CETP inhibitors after the HDL hypothesis was disregarded, as everyone thought these drugs were just about raising HDL. But actually, they can also lower LDL, and this particular agent reduces LDL very effectively,” Dr. Kastelein said.
 

ROSE study

Dr. Nicholls presented the latest data on obicetrapib at the AHA meeting.

“Despite the use of high-intensity statins, two-thirds of patients do not reach their target LDL level, so we have a need for new therapies that lower LDL and can be used in combination with high-intensity statins,” he explained.

He noted that earlier studies with obicetrapib showed a 45% lowering of LDL with monotherapy.

Dr. Nicholls reported that recent evidence has emerged that increases interest in inhibiting CETP to be potentially cardioprotective.

To begin, genetic studies have shown that genetic polymorphisms associated with lower levels of CETP appear to be cardioprotective, and this is associated with lower levels of LDL rather than higher levels of HDL. 

Furthermore, the REVEAL cardiovascular outcomes trial with anacetrapib (also a CETP inhibitor) in 2017 showed a significant 9% reduction in major adverse cardiac events (MACE) after 4 years of follow-up. “This was exactly predicted by the 11 mg/dL drop in absolute LDL cholesterol level. It was not predicted or associated with the increase in HDL level observed with that agent,” Dr. Nicholls said.

The objective of the current ROSE study was to evaluate the lipid-lowering ability, safety, and tolerability of obicetrapib in patients on high-intensity statins.

The study included 120 patients who had been treated on a stable dose of high-intensity statins (atorvastatin at a dose of at least 40 mg daily or rosuvastatin at a dose of 20 mg daily) for at least 8 weeks. All patients were required to have a fasting LDL of at least 70 mg/dL and the median baseline LDL was 90 mg/dL. They were randomly assigned to obicetrapib (5 mg or 10 mg daily) or placebo.

The primary endpoint was the difference between groups in percentage change in LDL from baseline to week 8, with LDL levels measured by two different techniques.

Results showed a “robust” 51% reduction in LDL with the 10-mg dose of obicetrapib, and a 42% reduction with the 5-mg dose, Dr. Nicholls reported.

These effects were comparable regardless of baseline LDL and were similar with both methods of LDL measurement. 

Almost all patients demonstrated some degree of LDL cholesterol lowering, with only three patients on the 5-mg dose and one patient on the 10-mg dose not showing any reduction in LDL.

Other results showed a dose-dependent lowering of Apo B of up to 30%, and a reduction of non-HDL cholesterol of up to 44%.

“Predictably, there were also increases of HDL cholesterol,” Dr. Nicholls said. “At the 10-mg dose, we see a 165% increase in HDL levels. That is associated with a 48% increase in Apo A1 levels. This is very consistent with findings from the previous monotherapy study.”  

There was a 56% reduction in Lp(a) levels, and a modest 11% reduction in triglycerides.

Both doses of obicetrapib were well tolerated, with no increase in the rate of adverse events. Only one patient discontinued the study drug because of an adverse event and that patient was in the placebo group, Dr. Nicholls noted.  

“Blood pressure is an important adverse event to look at in the CETP class given the challenges seen with the first CETP evaluated – torcetrapib,” Dr. Nicholls said. “But in the three clinical trials with obicetrapib conducted to date, reassuringly, we see no increase in either systolic or diastolic blood pressure with either the 5-mg or 10-mg dose.”

He concluded that obicetrapib “could be a valuable addition to high-risk patients with atherosclerotic cardiovascular disease who do not achieve their target LDL level despite use of high-intensity statin therapy.”
 

Differences from other CETP inhibitors

Asked how obicetrapib differs from other agents in the CETP inhibitor class, Dr. Nicholls replied that obicetrapib is much more potent, as shown by the large lipid changes seen with very small quantities of this drug, 5 mg or 10 mg, whereas prior CETP inhibitors showed smaller changes with much higher doses.

“We are giving very small amounts of obicetrapib and seeing very robust effects on both atherogenic and lipid parameters,” he said.  

“The other major point with this class of agent is that the first drug, torcetrapib, had toxicity, which resulted in increased cardiovascular events. But it has now been established that torcetrapib had a number of off-target effects that have not been seen with subsequent agents in this class,” he said.

Studies so far show that obicetrapib does not have torcetrapib-like effects. “That is encouraging. This, and the impressive LDL lowering effects, certainly lay the foundation for larger studies moving forward,” he added.

“This has been an intriguing field to many of us involved from the start. We started with a very disappointing result with torcetrapib. Then a couple of studies looked to be clinically futile, but we were encouraged by the REVEAL study which suggested that there might be benefit,” Dr. Nicholls said.

“If we combined the REVEAL results with the genetic data, it has actually flipped the whole CETP story upside down. We started thinking that inhibiting CETP was all about raising HDL, but it turns out that it is about LDL lowering,” he said. “And that is not only important in terms of the lipid effects but also the trials and the way they are designed.

“I think you’ll find that the future trials in this class and with this agent will have LDL very much in mind and that will very much influence the study design,” he said, adding that a larger cardiovascular outcome trial is now being planned. 

“The regulatory perspective is that LDL is a pretty trusted surrogate ... but I think an outcomes trial will be important to reinforce and reassure on safety and outline cost-effectiveness, which will help us understand where the sweet spot for using this agent in the clinic will be,” Dr. Nicholls noted.  

Dr. Kastelein explained that it has taken some time to realize that CETP inhibitors may be valuable for reducing LDL.   

“The first agent, torcetrapib, had an off-target toxicity that led to increased blood pressure but a specific part of the torcetrapib molecule was subsequently identified that was responsible for that, and subsequent agents in the CETP inhibitor class did not have such adverse effects,” he said.  

“The next agent, dalcetrapib (Roche), raised HDL but didn’t move LDL, and an outcomes trial with evacetrapib (Lilly) was stopped after 2 years because of futility, but we now believe that lipid lowering trials need longer term follow-up – up to 5 years – to see a benefit,” he noted.  

Dr. Kastelein reports that anacetrapib (Merck) has been the most powerful CETP inhibitor until now, giving an LDL reduction of about 20%, which was associated with a 10% reduction in cardiovascular events in first 4 years of follow-up. 

“Oxford academic researchers decided to continue follow-up in this trial without Merck and showed a 20% reduction in cardiovascular events by 6 years. This has been the strongest rationale for our investors,” Dr. Kastelein said.   

He pointed out that obicetrapib is much more potent than anacetrapib. “Obicetrapib reduces LDL by 50% at just a 10-mg dose, whereas anacetrapib was used at a dose of 100 mg to give a 17%-20% LDL reduction.”
 

Could HDL increase be beneficial after all?

Although increasing HDL is currently not thought to bring about a direct reduction in cardiovascular events, there is new evidence emerging that increasing HDL may confer some benefit in protecting against the development of type 2 diabetes, Dr. Kastelein noted.

“We know that statins can increase risk of developing type 2 diabetes, and post hoc analyses of previous trials with CETP inhibitors suggest that these drugs have the opposite effect,” he said. “We will investigate this protectively in our phase 3 outcomes trial. If this is a true effect, it should eventually translate into a reduction in cardiovascular outcomes, but this could take a longer time to see than the benefits of lowering LDL.”

Commenting on the current data, Steven Nissen, MD, of Cleveland Clinic, said: “The results are truly impressive – a nearly 50% LDL reduction on a background of statins with a once-daily oral agent. While PCSK9 inhibitors can achieve similar results, they are injectable and costly.

“Since anacetrapib, a much weaker CETP inhibitor, was successful at reducing major adverse cardiac events, the likelihood that obicetrapib would reduce MACE even more substantially is very high,” he added.

Dr. Nissen said he has been aware of this drug for some time and has advised the company about development options and regulatory strategy. “I have encouraged this company to develop this very promising drug,” he said.

The current study was funded by New Amsterdam Pharma. Dr. Nicholls reports grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, Infraredx, Roche, Sanofi-Regeneron and LipoScience, and honoraria from New Amsterdam Pharma, AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Kastelein is chief scientific officer of New Amsterdam Pharma.  

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

A new lipid-lowering agent in a class that had been written off by many is being developed by a group of academic experts, with new data showing large LDL reductions on top of high-intensity statins.

Obicetrapib is a member of the cholesteryl ester transfer protein (CETP) inhibitor class, which had fallen out of favor after several disappointments with previous drugs in this class.

These agents were initially developed for their ability to raise HDL cholesterol, which was thought to be beneficial. But that approach has now been virtually abandoned after several studies failed to show a link between raising HDL and a reduction in subsequent cardiovascular events.

However, obicetrapib, which is said to be the most potent CETP inhibitor to date, has been shown to produce impressive LDL reductions, and it’s this important data that has caused several lipid experts to want to continue its development.

New data, presented at the recent American Heart Association scientific sessions, show that obicetrapib reduces LDL by 50% when given in addition to high-intensity statins, which could place it as competition for PCSK9 inhibitors or the new agent, inclisiran, but with the advantage of oral dosing.

The drug was in development by Amgen, but the company decided to discontinue its development in 2017 after disappointing results had been seen with several other CETP inhibitors and interest in this class of agent was waning.

But academic experts in the lipid field, led by John Kastelein, MD, PhD, professor of medicine at the Academic Medical Center, University of Amsterdam, and Michael Davidson, MD, clinical professor of medicine at University of Chicago, believed the drug had potential and have acquired obicetrapib from Amgen.

Dr. Kastelein and Dr. Davidson have set up a new company – New Amsterdam Pharma – to further develop obicetrapib, and have raised $200 million from venture capital funding to complete phase 2 and phase 3 studies.

The company has a heavyweight academic advisory board including Stephen Nicholls, MD, Monash University, Clayton, Australia; Kausik Ray, MD, Imperial College London; and Christie Ballantyne, MD, Baylor College of Medicine, Houston.

“We wanted to develop obicetrapib further because of its amazing LDL-lowering properties,” Dr. Kastelein said in an interview.

“No one has paid much attention to CETP inhibitors after the HDL hypothesis was disregarded, as everyone thought these drugs were just about raising HDL. But actually, they can also lower LDL, and this particular agent reduces LDL very effectively,” Dr. Kastelein said.
 

ROSE study

Dr. Nicholls presented the latest data on obicetrapib at the AHA meeting.

“Despite the use of high-intensity statins, two-thirds of patients do not reach their target LDL level, so we have a need for new therapies that lower LDL and can be used in combination with high-intensity statins,” he explained.

He noted that earlier studies with obicetrapib showed a 45% lowering of LDL with monotherapy.

Dr. Nicholls reported that recent evidence has emerged that increases interest in inhibiting CETP to be potentially cardioprotective.

To begin, genetic studies have shown that genetic polymorphisms associated with lower levels of CETP appear to be cardioprotective, and this is associated with lower levels of LDL rather than higher levels of HDL. 

Furthermore, the REVEAL cardiovascular outcomes trial with anacetrapib (also a CETP inhibitor) in 2017 showed a significant 9% reduction in major adverse cardiac events (MACE) after 4 years of follow-up. “This was exactly predicted by the 11 mg/dL drop in absolute LDL cholesterol level. It was not predicted or associated with the increase in HDL level observed with that agent,” Dr. Nicholls said.

The objective of the current ROSE study was to evaluate the lipid-lowering ability, safety, and tolerability of obicetrapib in patients on high-intensity statins.

The study included 120 patients who had been treated on a stable dose of high-intensity statins (atorvastatin at a dose of at least 40 mg daily or rosuvastatin at a dose of 20 mg daily) for at least 8 weeks. All patients were required to have a fasting LDL of at least 70 mg/dL and the median baseline LDL was 90 mg/dL. They were randomly assigned to obicetrapib (5 mg or 10 mg daily) or placebo.

The primary endpoint was the difference between groups in percentage change in LDL from baseline to week 8, with LDL levels measured by two different techniques.

Results showed a “robust” 51% reduction in LDL with the 10-mg dose of obicetrapib, and a 42% reduction with the 5-mg dose, Dr. Nicholls reported.

These effects were comparable regardless of baseline LDL and were similar with both methods of LDL measurement. 

Almost all patients demonstrated some degree of LDL cholesterol lowering, with only three patients on the 5-mg dose and one patient on the 10-mg dose not showing any reduction in LDL.

Other results showed a dose-dependent lowering of Apo B of up to 30%, and a reduction of non-HDL cholesterol of up to 44%.

“Predictably, there were also increases of HDL cholesterol,” Dr. Nicholls said. “At the 10-mg dose, we see a 165% increase in HDL levels. That is associated with a 48% increase in Apo A1 levels. This is very consistent with findings from the previous monotherapy study.”  

There was a 56% reduction in Lp(a) levels, and a modest 11% reduction in triglycerides.

Both doses of obicetrapib were well tolerated, with no increase in the rate of adverse events. Only one patient discontinued the study drug because of an adverse event and that patient was in the placebo group, Dr. Nicholls noted.  

“Blood pressure is an important adverse event to look at in the CETP class given the challenges seen with the first CETP evaluated – torcetrapib,” Dr. Nicholls said. “But in the three clinical trials with obicetrapib conducted to date, reassuringly, we see no increase in either systolic or diastolic blood pressure with either the 5-mg or 10-mg dose.”

He concluded that obicetrapib “could be a valuable addition to high-risk patients with atherosclerotic cardiovascular disease who do not achieve their target LDL level despite use of high-intensity statin therapy.”
 

Differences from other CETP inhibitors

Asked how obicetrapib differs from other agents in the CETP inhibitor class, Dr. Nicholls replied that obicetrapib is much more potent, as shown by the large lipid changes seen with very small quantities of this drug, 5 mg or 10 mg, whereas prior CETP inhibitors showed smaller changes with much higher doses.

“We are giving very small amounts of obicetrapib and seeing very robust effects on both atherogenic and lipid parameters,” he said.  

“The other major point with this class of agent is that the first drug, torcetrapib, had toxicity, which resulted in increased cardiovascular events. But it has now been established that torcetrapib had a number of off-target effects that have not been seen with subsequent agents in this class,” he said.

Studies so far show that obicetrapib does not have torcetrapib-like effects. “That is encouraging. This, and the impressive LDL lowering effects, certainly lay the foundation for larger studies moving forward,” he added.

“This has been an intriguing field to many of us involved from the start. We started with a very disappointing result with torcetrapib. Then a couple of studies looked to be clinically futile, but we were encouraged by the REVEAL study which suggested that there might be benefit,” Dr. Nicholls said.

“If we combined the REVEAL results with the genetic data, it has actually flipped the whole CETP story upside down. We started thinking that inhibiting CETP was all about raising HDL, but it turns out that it is about LDL lowering,” he said. “And that is not only important in terms of the lipid effects but also the trials and the way they are designed.

“I think you’ll find that the future trials in this class and with this agent will have LDL very much in mind and that will very much influence the study design,” he said, adding that a larger cardiovascular outcome trial is now being planned. 

“The regulatory perspective is that LDL is a pretty trusted surrogate ... but I think an outcomes trial will be important to reinforce and reassure on safety and outline cost-effectiveness, which will help us understand where the sweet spot for using this agent in the clinic will be,” Dr. Nicholls noted.  

Dr. Kastelein explained that it has taken some time to realize that CETP inhibitors may be valuable for reducing LDL.   

“The first agent, torcetrapib, had an off-target toxicity that led to increased blood pressure but a specific part of the torcetrapib molecule was subsequently identified that was responsible for that, and subsequent agents in the CETP inhibitor class did not have such adverse effects,” he said.  

“The next agent, dalcetrapib (Roche), raised HDL but didn’t move LDL, and an outcomes trial with evacetrapib (Lilly) was stopped after 2 years because of futility, but we now believe that lipid lowering trials need longer term follow-up – up to 5 years – to see a benefit,” he noted.  

Dr. Kastelein reports that anacetrapib (Merck) has been the most powerful CETP inhibitor until now, giving an LDL reduction of about 20%, which was associated with a 10% reduction in cardiovascular events in first 4 years of follow-up. 

“Oxford academic researchers decided to continue follow-up in this trial without Merck and showed a 20% reduction in cardiovascular events by 6 years. This has been the strongest rationale for our investors,” Dr. Kastelein said.   

He pointed out that obicetrapib is much more potent than anacetrapib. “Obicetrapib reduces LDL by 50% at just a 10-mg dose, whereas anacetrapib was used at a dose of 100 mg to give a 17%-20% LDL reduction.”
 

Could HDL increase be beneficial after all?

Although increasing HDL is currently not thought to bring about a direct reduction in cardiovascular events, there is new evidence emerging that increasing HDL may confer some benefit in protecting against the development of type 2 diabetes, Dr. Kastelein noted.

“We know that statins can increase risk of developing type 2 diabetes, and post hoc analyses of previous trials with CETP inhibitors suggest that these drugs have the opposite effect,” he said. “We will investigate this protectively in our phase 3 outcomes trial. If this is a true effect, it should eventually translate into a reduction in cardiovascular outcomes, but this could take a longer time to see than the benefits of lowering LDL.”

Commenting on the current data, Steven Nissen, MD, of Cleveland Clinic, said: “The results are truly impressive – a nearly 50% LDL reduction on a background of statins with a once-daily oral agent. While PCSK9 inhibitors can achieve similar results, they are injectable and costly.

“Since anacetrapib, a much weaker CETP inhibitor, was successful at reducing major adverse cardiac events, the likelihood that obicetrapib would reduce MACE even more substantially is very high,” he added.

Dr. Nissen said he has been aware of this drug for some time and has advised the company about development options and regulatory strategy. “I have encouraged this company to develop this very promising drug,” he said.

The current study was funded by New Amsterdam Pharma. Dr. Nicholls reports grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, Infraredx, Roche, Sanofi-Regeneron and LipoScience, and honoraria from New Amsterdam Pharma, AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Kastelein is chief scientific officer of New Amsterdam Pharma.  

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

Going to bed later than usual and/or getting a poor night’s sleep are both associated with impaired glycemic response to breakfast the following morning in healthy adults, according to a multiple test-meal challenge study conducted over 14 days.

“Our data suggest that sleep duration, efficiency, and midpoint are important determinants of postprandial glycemic control at a population level,” Neil Tsereteli, MD, Lund University Diabetes Centre, Malmo, Sweden, and colleagues wrote in their article, published online Nov. 30, 2021, in Diabetologia.

“And [the results] suggest that one-size-fits-all sleep recommendations are suboptimal, particularly in the context of postprandial glycemic control, a key component of diabetes prevention,” they added.
 

Prior research on sleep quality and control of glucose lacking

Diet, exercise, and sleep are fundamental components of a healthy lifestyle; however, the role that sleep plays in affecting blood glucose control in generally healthy people has been studied little so far, the researchers wrote.

Sleep disorders can act as a measure of general health as they often occur alongside other health problems. Sleep quality also has a direct causal effect on many conditions such as cardiovascular disease, obesity, and type 2 diabetes. And disturbed sleep caused by conditions such as obstructive sleep apnea is associated with the prevalence of type 2 diabetes and risk of associated complications.

This and other evidence suggest a strong link between glucose regulation and the quality and duration of sleep.

Dr. Tsereteli and colleagues set out to examine this further in the Personalized Responses to Dietary Composition Trial 1, which involved 953 healthy adults who consumed standardized meals over 2 weeks in a clinic setting and at home.

“The meals were consumed either for breakfast or lunch in a randomized meal order and consisted of eight different standardized meals,”  the researchers wrote.

Activity and sleep were monitored using a wearable device with an accelerometer. Postprandial blood glucose levels were measured using a continuous glucose monitor.

Sleep variables including quality, duration, and timing and their impact on glycemic response to breakfast the following morning, and were compared between participants and within each individual.
 

Better sleep efficiency, better glucose control

The study found that, although there was no significant association between length of sleep period and postmeal glycemic response, there was a significant interaction when the nutritional content of the breakfast meal was also considered.

Longer sleep periods were associated with lower blood glucose following high-carbohydrate and high-fat breakfasts, indicating better blood glucose control.

Additionally, the researchers observed a within-person effect in which a study participant who slept for longer than they typically would was likely to have reduced postprandial blood glucose following a high-carbohydrate or high-fat breakfast the next day.

The authors also found a significant link between sleep efficiency (ratio of time asleep to total length of sleep period) and glycemic control. When a participant slept more efficiently than usual, their postprandial blood glucose also tended to be lower than usual.

“This effect was largely driven by sleep onset (going to bed later) rather than sleep offset (waking up later),” Dr. Tsereteli and colleagues noted.
 

Sleep a key pillar of health

Asked whether these particular sleep effects might be exacerbated in patients with diabetes, senior author Paul Franks, MD, also from the Lund University Diabetes Centre, felt they could not meaningfully extrapolate results to people with diabetes, given that many take glucose-lowering medications.

“However, it is likely that these results would be similar or exacerbated in people with prediabetes, as glucose fluctuations in this subgroup of patients are generally greater than in people with normoglycemia,” he noted in an interview.

“Sleep is a key pillar of health, and focusing on both sleep and diet is key for healthy blood glucose control,” he added.

“Compensating for a bad night’s sleep by consuming a very sugary breakfast or energy drinks is likely to be especially detrimental for blood glucose control,” Dr. Franks said.

The study was funded by Lund University. Dr. Tsereteli and Dr. Franks reported no relevant financial relationships.

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

Going to bed later than usual and/or getting a poor night’s sleep are both associated with impaired glycemic response to breakfast the following morning in healthy adults, according to a multiple test-meal challenge study conducted over 14 days.

“Our data suggest that sleep duration, efficiency, and midpoint are important determinants of postprandial glycemic control at a population level,” Neil Tsereteli, MD, Lund University Diabetes Centre, Malmo, Sweden, and colleagues wrote in their article, published online Nov. 30, 2021, in Diabetologia.

“And [the results] suggest that one-size-fits-all sleep recommendations are suboptimal, particularly in the context of postprandial glycemic control, a key component of diabetes prevention,” they added.
 

Prior research on sleep quality and control of glucose lacking

Diet, exercise, and sleep are fundamental components of a healthy lifestyle; however, the role that sleep plays in affecting blood glucose control in generally healthy people has been studied little so far, the researchers wrote.

Sleep disorders can act as a measure of general health as they often occur alongside other health problems. Sleep quality also has a direct causal effect on many conditions such as cardiovascular disease, obesity, and type 2 diabetes. And disturbed sleep caused by conditions such as obstructive sleep apnea is associated with the prevalence of type 2 diabetes and risk of associated complications.

This and other evidence suggest a strong link between glucose regulation and the quality and duration of sleep.

Dr. Tsereteli and colleagues set out to examine this further in the Personalized Responses to Dietary Composition Trial 1, which involved 953 healthy adults who consumed standardized meals over 2 weeks in a clinic setting and at home.

“The meals were consumed either for breakfast or lunch in a randomized meal order and consisted of eight different standardized meals,”  the researchers wrote.

Activity and sleep were monitored using a wearable device with an accelerometer. Postprandial blood glucose levels were measured using a continuous glucose monitor.

Sleep variables including quality, duration, and timing and their impact on glycemic response to breakfast the following morning, and were compared between participants and within each individual.
 

Better sleep efficiency, better glucose control

The study found that, although there was no significant association between length of sleep period and postmeal glycemic response, there was a significant interaction when the nutritional content of the breakfast meal was also considered.

Longer sleep periods were associated with lower blood glucose following high-carbohydrate and high-fat breakfasts, indicating better blood glucose control.

Additionally, the researchers observed a within-person effect in which a study participant who slept for longer than they typically would was likely to have reduced postprandial blood glucose following a high-carbohydrate or high-fat breakfast the next day.

The authors also found a significant link between sleep efficiency (ratio of time asleep to total length of sleep period) and glycemic control. When a participant slept more efficiently than usual, their postprandial blood glucose also tended to be lower than usual.

“This effect was largely driven by sleep onset (going to bed later) rather than sleep offset (waking up later),” Dr. Tsereteli and colleagues noted.
 

Sleep a key pillar of health

Asked whether these particular sleep effects might be exacerbated in patients with diabetes, senior author Paul Franks, MD, also from the Lund University Diabetes Centre, felt they could not meaningfully extrapolate results to people with diabetes, given that many take glucose-lowering medications.

“However, it is likely that these results would be similar or exacerbated in people with prediabetes, as glucose fluctuations in this subgroup of patients are generally greater than in people with normoglycemia,” he noted in an interview.

“Sleep is a key pillar of health, and focusing on both sleep and diet is key for healthy blood glucose control,” he added.

“Compensating for a bad night’s sleep by consuming a very sugary breakfast or energy drinks is likely to be especially detrimental for blood glucose control,” Dr. Franks said.

The study was funded by Lund University. Dr. Tsereteli and Dr. Franks reported no relevant financial relationships.

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

Going to bed later than usual and/or getting a poor night’s sleep are both associated with impaired glycemic response to breakfast the following morning in healthy adults, according to a multiple test-meal challenge study conducted over 14 days.

“Our data suggest that sleep duration, efficiency, and midpoint are important determinants of postprandial glycemic control at a population level,” Neil Tsereteli, MD, Lund University Diabetes Centre, Malmo, Sweden, and colleagues wrote in their article, published online Nov. 30, 2021, in Diabetologia.

“And [the results] suggest that one-size-fits-all sleep recommendations are suboptimal, particularly in the context of postprandial glycemic control, a key component of diabetes prevention,” they added.
 

Prior research on sleep quality and control of glucose lacking

Diet, exercise, and sleep are fundamental components of a healthy lifestyle; however, the role that sleep plays in affecting blood glucose control in generally healthy people has been studied little so far, the researchers wrote.

Sleep disorders can act as a measure of general health as they often occur alongside other health problems. Sleep quality also has a direct causal effect on many conditions such as cardiovascular disease, obesity, and type 2 diabetes. And disturbed sleep caused by conditions such as obstructive sleep apnea is associated with the prevalence of type 2 diabetes and risk of associated complications.

This and other evidence suggest a strong link between glucose regulation and the quality and duration of sleep.

Dr. Tsereteli and colleagues set out to examine this further in the Personalized Responses to Dietary Composition Trial 1, which involved 953 healthy adults who consumed standardized meals over 2 weeks in a clinic setting and at home.

“The meals were consumed either for breakfast or lunch in a randomized meal order and consisted of eight different standardized meals,”  the researchers wrote.

Activity and sleep were monitored using a wearable device with an accelerometer. Postprandial blood glucose levels were measured using a continuous glucose monitor.

Sleep variables including quality, duration, and timing and their impact on glycemic response to breakfast the following morning, and were compared between participants and within each individual.
 

Better sleep efficiency, better glucose control

The study found that, although there was no significant association between length of sleep period and postmeal glycemic response, there was a significant interaction when the nutritional content of the breakfast meal was also considered.

Longer sleep periods were associated with lower blood glucose following high-carbohydrate and high-fat breakfasts, indicating better blood glucose control.

Additionally, the researchers observed a within-person effect in which a study participant who slept for longer than they typically would was likely to have reduced postprandial blood glucose following a high-carbohydrate or high-fat breakfast the next day.

The authors also found a significant link between sleep efficiency (ratio of time asleep to total length of sleep period) and glycemic control. When a participant slept more efficiently than usual, their postprandial blood glucose also tended to be lower than usual.

“This effect was largely driven by sleep onset (going to bed later) rather than sleep offset (waking up later),” Dr. Tsereteli and colleagues noted.
 

Sleep a key pillar of health

Asked whether these particular sleep effects might be exacerbated in patients with diabetes, senior author Paul Franks, MD, also from the Lund University Diabetes Centre, felt they could not meaningfully extrapolate results to people with diabetes, given that many take glucose-lowering medications.

“However, it is likely that these results would be similar or exacerbated in people with prediabetes, as glucose fluctuations in this subgroup of patients are generally greater than in people with normoglycemia,” he noted in an interview.

“Sleep is a key pillar of health, and focusing on both sleep and diet is key for healthy blood glucose control,” he added.

“Compensating for a bad night’s sleep by consuming a very sugary breakfast or energy drinks is likely to be especially detrimental for blood glucose control,” Dr. Franks said.

The study was funded by Lund University. Dr. Tsereteli and Dr. Franks reported no relevant financial relationships.

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

Early lab studies show that a COVID-19 antibody treatment developed by GlaxoSmithKline and Vir Biotechnology could be effective against the Omicron variant.

The companies said Dec. 2 that they tested the drug, called sotrovimab, against individual mutations found in the Omicron variant, according to The Wall Street Journal. The preliminary findings haven’t yet been peer-reviewed, and the drug will need to be tested against the whole spike protein on the virus to confirm results.

GlaxoSmithKline and Vir have previously tested sotrovimab against mutations on other variants, the newspaper reported. When the Omicron variant was identified, the companies looked at earlier research to find the tests they had done against mutations that are also found in Omicron.

Sotrovimab targets a spot on the spike protein that is found in other coronaviruses and is thought to be less likely to mutate, according to the newspaper. Omicron has at least two mutations that overlap with the drug’s target site, but researchers at the companies don’t think the mutations will affect the treatment’s ability to bind to the spike protein.

GlaxoSmithKline expects to see results from testing the drug against the full mutated spike protein in the next 2 to 3 weeks, the Journal reported.

Sotrovimab has been authorized in about a dozen countries, including the United States, which paid about $1 billion for hundreds of thousands of doses.

Other companies have also been testing their antibody treatments against the Omicron variant.

Regeneron announced Nov. 30 that its drug could be less effective, and it said further analyses will determine how much less effective by using the actual Omicron genetic sequence, according to Reuters.

Outside scientists have also said the antibody drug from Eli Lilly & Co. isn’t as effective against Omicron. The company told Reuters that it is still testing the treatment against the variant.

Another experimental antibody therapy developed by Adagio Therapeutics appears to work well against the new variant, the Journal reported, but the treatment is in late-stage clinical trials and isn’t yet authorized.

Antiviral drugs could also help prevent hospitalization and may be less vulnerable to new variants because they target a different part of the virus, the newspaper reported. Merck and Pfizer have developed antiviral pills, which still require FDA approval.

In addition, Gilead believes its approved IV therapy, called remdesivir, will continue to be effective against the variant, Reuters reported.

The FDA said Nov. 30 that it is looking at the effect that authorized COVID-19 vaccines can have on Omicron and expects to have more information in coming weeks, Reuters reported.

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

Early lab studies show that a COVID-19 antibody treatment developed by GlaxoSmithKline and Vir Biotechnology could be effective against the Omicron variant.

The companies said Dec. 2 that they tested the drug, called sotrovimab, against individual mutations found in the Omicron variant, according to The Wall Street Journal. The preliminary findings haven’t yet been peer-reviewed, and the drug will need to be tested against the whole spike protein on the virus to confirm results.

GlaxoSmithKline and Vir have previously tested sotrovimab against mutations on other variants, the newspaper reported. When the Omicron variant was identified, the companies looked at earlier research to find the tests they had done against mutations that are also found in Omicron.

Sotrovimab targets a spot on the spike protein that is found in other coronaviruses and is thought to be less likely to mutate, according to the newspaper. Omicron has at least two mutations that overlap with the drug’s target site, but researchers at the companies don’t think the mutations will affect the treatment’s ability to bind to the spike protein.

GlaxoSmithKline expects to see results from testing the drug against the full mutated spike protein in the next 2 to 3 weeks, the Journal reported.

Sotrovimab has been authorized in about a dozen countries, including the United States, which paid about $1 billion for hundreds of thousands of doses.

Other companies have also been testing their antibody treatments against the Omicron variant.

Regeneron announced Nov. 30 that its drug could be less effective, and it said further analyses will determine how much less effective by using the actual Omicron genetic sequence, according to Reuters.

Outside scientists have also said the antibody drug from Eli Lilly & Co. isn’t as effective against Omicron. The company told Reuters that it is still testing the treatment against the variant.

Another experimental antibody therapy developed by Adagio Therapeutics appears to work well against the new variant, the Journal reported, but the treatment is in late-stage clinical trials and isn’t yet authorized.

Antiviral drugs could also help prevent hospitalization and may be less vulnerable to new variants because they target a different part of the virus, the newspaper reported. Merck and Pfizer have developed antiviral pills, which still require FDA approval.

In addition, Gilead believes its approved IV therapy, called remdesivir, will continue to be effective against the variant, Reuters reported.

The FDA said Nov. 30 that it is looking at the effect that authorized COVID-19 vaccines can have on Omicron and expects to have more information in coming weeks, Reuters reported.

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

Early lab studies show that a COVID-19 antibody treatment developed by GlaxoSmithKline and Vir Biotechnology could be effective against the Omicron variant.

The companies said Dec. 2 that they tested the drug, called sotrovimab, against individual mutations found in the Omicron variant, according to The Wall Street Journal. The preliminary findings haven’t yet been peer-reviewed, and the drug will need to be tested against the whole spike protein on the virus to confirm results.

GlaxoSmithKline and Vir have previously tested sotrovimab against mutations on other variants, the newspaper reported. When the Omicron variant was identified, the companies looked at earlier research to find the tests they had done against mutations that are also found in Omicron.

Sotrovimab targets a spot on the spike protein that is found in other coronaviruses and is thought to be less likely to mutate, according to the newspaper. Omicron has at least two mutations that overlap with the drug’s target site, but researchers at the companies don’t think the mutations will affect the treatment’s ability to bind to the spike protein.

GlaxoSmithKline expects to see results from testing the drug against the full mutated spike protein in the next 2 to 3 weeks, the Journal reported.

Sotrovimab has been authorized in about a dozen countries, including the United States, which paid about $1 billion for hundreds of thousands of doses.

Other companies have also been testing their antibody treatments against the Omicron variant.

Regeneron announced Nov. 30 that its drug could be less effective, and it said further analyses will determine how much less effective by using the actual Omicron genetic sequence, according to Reuters.

Outside scientists have also said the antibody drug from Eli Lilly & Co. isn’t as effective against Omicron. The company told Reuters that it is still testing the treatment against the variant.

Another experimental antibody therapy developed by Adagio Therapeutics appears to work well against the new variant, the Journal reported, but the treatment is in late-stage clinical trials and isn’t yet authorized.

Antiviral drugs could also help prevent hospitalization and may be less vulnerable to new variants because they target a different part of the virus, the newspaper reported. Merck and Pfizer have developed antiviral pills, which still require FDA approval.

In addition, Gilead believes its approved IV therapy, called remdesivir, will continue to be effective against the variant, Reuters reported.

The FDA said Nov. 30 that it is looking at the effect that authorized COVID-19 vaccines can have on Omicron and expects to have more information in coming weeks, Reuters reported.

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

Clinicians need to pay more attention to high levels of lipoprotein cholesterol (LDL-C) – a marker of cardiovascular disease (CVD) risk – in patients with type 2 diabetes, a new population-based study in Finland suggests.

In the study, recently published online in Scientific Reports , the authors showed that LDL-C control and statin prescriptions remain suboptimal in this patient population in clinical practice.

They identified four 5-year trajectories of LDL-C along with concurrent levels of statin treatment. The percentages of patients in each group were:

• Moderately stable LDL-C: 2.3 mmol/L (90 mg/dL): 86%  
• High stable LDL-C: 3.9 mmol/L (152 mg/dL): 7.7%
• Decreasing LDL-C: 3.8%
• Increasing LDL-C: 2.5% 

“The second-largest group consisted of predominantly untreated patients (7.7%) with alarmingly ‘high stable’ LDL-C levels around 3.9 mmol/L,” the researchers noted.

And among patients with “increasing” LDL-C cholesterol, statin treatment “declined drastically.”

Moreover, 42% of patients had no statins prescribed at the end of follow-up.

These findings show that “efforts to control LDL-C should be increased – especially in patients with continuously elevated levels – by initiating and intensifying statin treatment earlier and reinitiating the treatment after discontinuation, if possible,” lead author Laura Inglin, MPH, told this news organization.
 

Discuss risks vs. benefits of statins with patients

Patients may not understand the benefits versus potential side effects of statins, said Ms. Inglin, of the Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio.

To improve management of cholesterol levels, she said, “clinician-patient discussions are crucial, addressing risk/benefits and treatment goals, and offering reputable sources” of information about statins.

When patients discontinue statin treatment, Ms. Inglin continued, “physicians should try to reinitiate another statin or to lower the dose if possible, following guidelines on how to do that,” as other research has reported that more than 70% of patients who stopped a statin because of side effects tolerated it when it was restarted.

The study also identified gender differences, she continued. Compared with men, women had significantly higher average LDL-C levels, but were less likely to be prescribed a statin or were prescribed a lower-dose statin, and they were more likely to discontinue statin therapy. 
 

Four LDL-C trajectories with statin treatment differences

Suboptimal lipid profiles, especially elevated LDL-C, are strongly associated with atherosclerotic CVD in individuals with type 2 diabetes, Ms. Inglin and colleagues write.

“To prevent or at least delay complications, regular follow-up visits and good control of A1c, LDL-C, blood pressure, and other CVD risk factors are vital in diabetes management,” they continued. “Guidelines have consistently identified statins as the principal lipid-lowering therapy, recommended particularly at moderate- to high-intensity.” 

The researchers aimed to identify LDL-C level trajectories and concomitant statin treatment in patients with type 2 diabetes.

They identified 8,592 patients – 4,622 men (54%) and 3,970 women (46%) – with type 2 diabetes seen by primary care physicians or specialists in North Karelia, Eastern Finland, during 2011-2017.

As with other international guidelines, the Finnish Current Care Guideline recommended assessing LDL-C levels every 1-3 years in patients with type 2 diabetes, with LDL-C treatment targets of < 2.5 mmol/L (< 100 mg/dL) for those at high CVD risk due to diabetes, and targets of < 1.8 mmol/L (< 70 mg/dL) or a 50% reduction from baseline in those at very high CVD risk due to additional risk factors.

At baseline, on average, men in the current study were aged 66 years and had had diabetes for 8 years; 60% were receiving a statin and 56% had an LDL-C < 2.5 mmol/L.

Women were, on average, age 69 years and had had diabetes for 8 years; 56% were receiving a statin and 51% had an LDL-C < 2.5 mmol/L.

The researchers identified the four distinct LDL-C trajectories, each with differences in statin treatment.

In the “moderate-stable” LDL-C group, 67% of men and 64% of women were receiving a statin, and the rates of high-intensity statin increased in both men and women.

In the “high-stable” LDL-C group, rates of statin use decreased from 42% to 27% among men and from 34% to 23% among women.

In the “decreasing” LDL-C group, the proportion of patients who received a statin increased; the percentage of patients who received a high-intensity statin also increased among men (6.2% to 29%) and women (7.7% to 14%).

In the “increasing” LDL-C group, the percentage of patients receiving a statin decreased from more than 64% to less than 43%.

“Physicians should increase efforts to achieve the LDL-C treatment targets – especially in the patient group with constantly elevated LDL-C levels – by paying attention to earlier initiation of statin treatment, intensification of treatments when necessary, and reinitiating if possible,” the researchers reiterated.

“The results of our study may support physicians to identify patients who need to be monitored more closely beyond a single time point measurement,” they concluded.

The study was partly funded by the Strategic Research Council of the Academy of Finland (project IMPRO), the Finnish Diabetes Association, and the Research Committee of the Kuopio University Hospital Catchment Area for the State Research Funding (project QCARE). The authors have reported no relevant financial relationships.

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

Clinicians need to pay more attention to high levels of lipoprotein cholesterol (LDL-C) – a marker of cardiovascular disease (CVD) risk – in patients with type 2 diabetes, a new population-based study in Finland suggests.

In the study, recently published online in Scientific Reports , the authors showed that LDL-C control and statin prescriptions remain suboptimal in this patient population in clinical practice.

They identified four 5-year trajectories of LDL-C along with concurrent levels of statin treatment. The percentages of patients in each group were:

• Moderately stable LDL-C: 2.3 mmol/L (90 mg/dL): 86%  
• High stable LDL-C: 3.9 mmol/L (152 mg/dL): 7.7%
• Decreasing LDL-C: 3.8%
• Increasing LDL-C: 2.5% 

“The second-largest group consisted of predominantly untreated patients (7.7%) with alarmingly ‘high stable’ LDL-C levels around 3.9 mmol/L,” the researchers noted.

And among patients with “increasing” LDL-C cholesterol, statin treatment “declined drastically.”

Moreover, 42% of patients had no statins prescribed at the end of follow-up.

These findings show that “efforts to control LDL-C should be increased – especially in patients with continuously elevated levels – by initiating and intensifying statin treatment earlier and reinitiating the treatment after discontinuation, if possible,” lead author Laura Inglin, MPH, told this news organization.
 

Discuss risks vs. benefits of statins with patients

Patients may not understand the benefits versus potential side effects of statins, said Ms. Inglin, of the Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio.

To improve management of cholesterol levels, she said, “clinician-patient discussions are crucial, addressing risk/benefits and treatment goals, and offering reputable sources” of information about statins.

When patients discontinue statin treatment, Ms. Inglin continued, “physicians should try to reinitiate another statin or to lower the dose if possible, following guidelines on how to do that,” as other research has reported that more than 70% of patients who stopped a statin because of side effects tolerated it when it was restarted.

The study also identified gender differences, she continued. Compared with men, women had significantly higher average LDL-C levels, but were less likely to be prescribed a statin or were prescribed a lower-dose statin, and they were more likely to discontinue statin therapy. 
 

Four LDL-C trajectories with statin treatment differences

Suboptimal lipid profiles, especially elevated LDL-C, are strongly associated with atherosclerotic CVD in individuals with type 2 diabetes, Ms. Inglin and colleagues write.

“To prevent or at least delay complications, regular follow-up visits and good control of A1c, LDL-C, blood pressure, and other CVD risk factors are vital in diabetes management,” they continued. “Guidelines have consistently identified statins as the principal lipid-lowering therapy, recommended particularly at moderate- to high-intensity.” 

The researchers aimed to identify LDL-C level trajectories and concomitant statin treatment in patients with type 2 diabetes.

They identified 8,592 patients – 4,622 men (54%) and 3,970 women (46%) – with type 2 diabetes seen by primary care physicians or specialists in North Karelia, Eastern Finland, during 2011-2017.

As with other international guidelines, the Finnish Current Care Guideline recommended assessing LDL-C levels every 1-3 years in patients with type 2 diabetes, with LDL-C treatment targets of < 2.5 mmol/L (< 100 mg/dL) for those at high CVD risk due to diabetes, and targets of < 1.8 mmol/L (< 70 mg/dL) or a 50% reduction from baseline in those at very high CVD risk due to additional risk factors.

At baseline, on average, men in the current study were aged 66 years and had had diabetes for 8 years; 60% were receiving a statin and 56% had an LDL-C < 2.5 mmol/L.

Women were, on average, age 69 years and had had diabetes for 8 years; 56% were receiving a statin and 51% had an LDL-C < 2.5 mmol/L.

The researchers identified the four distinct LDL-C trajectories, each with differences in statin treatment.

In the “moderate-stable” LDL-C group, 67% of men and 64% of women were receiving a statin, and the rates of high-intensity statin increased in both men and women.

In the “high-stable” LDL-C group, rates of statin use decreased from 42% to 27% among men and from 34% to 23% among women.

In the “decreasing” LDL-C group, the proportion of patients who received a statin increased; the percentage of patients who received a high-intensity statin also increased among men (6.2% to 29%) and women (7.7% to 14%).

In the “increasing” LDL-C group, the percentage of patients receiving a statin decreased from more than 64% to less than 43%.

“Physicians should increase efforts to achieve the LDL-C treatment targets – especially in the patient group with constantly elevated LDL-C levels – by paying attention to earlier initiation of statin treatment, intensification of treatments when necessary, and reinitiating if possible,” the researchers reiterated.

“The results of our study may support physicians to identify patients who need to be monitored more closely beyond a single time point measurement,” they concluded.

The study was partly funded by the Strategic Research Council of the Academy of Finland (project IMPRO), the Finnish Diabetes Association, and the Research Committee of the Kuopio University Hospital Catchment Area for the State Research Funding (project QCARE). The authors have reported no relevant financial relationships.

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

Clinicians need to pay more attention to high levels of lipoprotein cholesterol (LDL-C) – a marker of cardiovascular disease (CVD) risk – in patients with type 2 diabetes, a new population-based study in Finland suggests.

In the study, recently published online in Scientific Reports , the authors showed that LDL-C control and statin prescriptions remain suboptimal in this patient population in clinical practice.

They identified four 5-year trajectories of LDL-C along with concurrent levels of statin treatment. The percentages of patients in each group were:

• Moderately stable LDL-C: 2.3 mmol/L (90 mg/dL): 86%  
• High stable LDL-C: 3.9 mmol/L (152 mg/dL): 7.7%
• Decreasing LDL-C: 3.8%
• Increasing LDL-C: 2.5% 

“The second-largest group consisted of predominantly untreated patients (7.7%) with alarmingly ‘high stable’ LDL-C levels around 3.9 mmol/L,” the researchers noted.

And among patients with “increasing” LDL-C cholesterol, statin treatment “declined drastically.”

Moreover, 42% of patients had no statins prescribed at the end of follow-up.

These findings show that “efforts to control LDL-C should be increased – especially in patients with continuously elevated levels – by initiating and intensifying statin treatment earlier and reinitiating the treatment after discontinuation, if possible,” lead author Laura Inglin, MPH, told this news organization.
 

Discuss risks vs. benefits of statins with patients

Patients may not understand the benefits versus potential side effects of statins, said Ms. Inglin, of the Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio.

To improve management of cholesterol levels, she said, “clinician-patient discussions are crucial, addressing risk/benefits and treatment goals, and offering reputable sources” of information about statins.

When patients discontinue statin treatment, Ms. Inglin continued, “physicians should try to reinitiate another statin or to lower the dose if possible, following guidelines on how to do that,” as other research has reported that more than 70% of patients who stopped a statin because of side effects tolerated it when it was restarted.

The study also identified gender differences, she continued. Compared with men, women had significantly higher average LDL-C levels, but were less likely to be prescribed a statin or were prescribed a lower-dose statin, and they were more likely to discontinue statin therapy. 
 

Four LDL-C trajectories with statin treatment differences

Suboptimal lipid profiles, especially elevated LDL-C, are strongly associated with atherosclerotic CVD in individuals with type 2 diabetes, Ms. Inglin and colleagues write.

“To prevent or at least delay complications, regular follow-up visits and good control of A1c, LDL-C, blood pressure, and other CVD risk factors are vital in diabetes management,” they continued. “Guidelines have consistently identified statins as the principal lipid-lowering therapy, recommended particularly at moderate- to high-intensity.” 

The researchers aimed to identify LDL-C level trajectories and concomitant statin treatment in patients with type 2 diabetes.

They identified 8,592 patients – 4,622 men (54%) and 3,970 women (46%) – with type 2 diabetes seen by primary care physicians or specialists in North Karelia, Eastern Finland, during 2011-2017.

As with other international guidelines, the Finnish Current Care Guideline recommended assessing LDL-C levels every 1-3 years in patients with type 2 diabetes, with LDL-C treatment targets of < 2.5 mmol/L (< 100 mg/dL) for those at high CVD risk due to diabetes, and targets of < 1.8 mmol/L (< 70 mg/dL) or a 50% reduction from baseline in those at very high CVD risk due to additional risk factors.

At baseline, on average, men in the current study were aged 66 years and had had diabetes for 8 years; 60% were receiving a statin and 56% had an LDL-C < 2.5 mmol/L.

Women were, on average, age 69 years and had had diabetes for 8 years; 56% were receiving a statin and 51% had an LDL-C < 2.5 mmol/L.

The researchers identified the four distinct LDL-C trajectories, each with differences in statin treatment.

In the “moderate-stable” LDL-C group, 67% of men and 64% of women were receiving a statin, and the rates of high-intensity statin increased in both men and women.

In the “high-stable” LDL-C group, rates of statin use decreased from 42% to 27% among men and from 34% to 23% among women.

In the “decreasing” LDL-C group, the proportion of patients who received a statin increased; the percentage of patients who received a high-intensity statin also increased among men (6.2% to 29%) and women (7.7% to 14%).

In the “increasing” LDL-C group, the percentage of patients receiving a statin decreased from more than 64% to less than 43%.

“Physicians should increase efforts to achieve the LDL-C treatment targets – especially in the patient group with constantly elevated LDL-C levels – by paying attention to earlier initiation of statin treatment, intensification of treatments when necessary, and reinitiating if possible,” the researchers reiterated.

“The results of our study may support physicians to identify patients who need to be monitored more closely beyond a single time point measurement,” they concluded.

The study was partly funded by the Strategic Research Council of the Academy of Finland (project IMPRO), the Finnish Diabetes Association, and the Research Committee of the Kuopio University Hospital Catchment Area for the State Research Funding (project QCARE). The authors have reported no relevant financial relationships.

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

COVID-19’s relentless toll on the clinical workforce inspired four doctors to draft an action plan to stem the exits and help colleagues preserve their physical and mental health.

Indeed, a recent poll of 1,000 health care workers conducted Sept. 2-8 by Morning Consult, showed that 18% of medical workers polled quit their jobs during the pandemic. Additionally, 31% said they had at least thought about leaving their work.

“As physicians, educators, peers and friends of COVID-19 responders, we are gravely concerned about our colleagues’ exhaustion, burnout, and disillusionment,” wrote lead author Eileen Barrett, MD, and coauthors of the new action plan, which was published in the Annals of Internal Medicine.

The 10-point, one-page checklist includes providing “practical support in the areas that clinicians identify as causing emotional stress or moral injury,” such as managing anger and grief when patients have chosen not to be vaccinated or confronting misinformation.

“Those are the things that are making people’s mental health worse” psychiatrist Jessi Gold, MD, MS, said in an interview. “I don’t think I’ve seen that mentioned other places.”

Among the other action items are:

• Reduce administrative tasks that are not “mission critical,” such as mandatory training that has no evidence of improving patient outcomes and meetings that could be skipped.
• Offer free and confidential resources to support clinicians’ mental health, such as easy access to crisis hotlines and peer support groups.
• Maintain transparency about personal protective equipment and contingency plans when there are shortages to restore trust.
• Encourage clinicians to use vacation time; leaders should model this.
• Implement suicide prevention strategies, including wellness check-ins for clinicians in hard-hit areas.

The action plan was based on the authors’ own experiences and the stories of colleagues and information in literature. It includes 10 changes health care leaders could make to help retain providers who may be on the brink of leaving their jobs or leaving medicine

Action items intended to be easily achievable, low cost

Dr. Barrett, who is a hospitalist in Albuquerque, said the goal was to present easily achievable and low-cost action items that clinicians and health care leaders could use as a starting point when change seems insurmountable and evidence on what works is slow to come.

She said one of the things that spurred her to coauthor the list was becoming aware of other clinicians’ “secret shame” in thinking about leaving medicine.

“Maybe a person who is not being listened to could take this journal article and say ‘we don’t know where to start. It looks like we can start here,’ ” said Dr. Barrett, who is also an associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.

She noted that some of the good ideas floated around did not make the list, because they required daunting budget commitments and too much time to put into place.

Numerous other proposed solutions were of the wrong tone, according to Dr. Barrett.

“It’s not just about a hug or a piece of pizza,” she said.

Dr. Gold, who is an assistant professor at Washington University, St. Louis, and specializes in the mental health of health care workers, noted that, even though the list was pared to 10 action items, it is still hard for health care organizations to prioritize mental health.

“Many hospitals are still struggling with the active bleed of the pandemic and financially recovering,” she said. “If you’re dealing with a full ER and people are still dying of COVID and you don’t have the resources to support them, it’s really hard to then find magic money to deal with mental health. I’d love for that to be true.”

Every organization, however, can start with removing questions about mental and physical health diagnoses from credentialing and employment applications, which is one of the items on the list, she said.

“It’s the lowest-bar thing that you can fix for making people in crisis not fear getting help,” she said. That change must come on a state-by-state and individual hospital level.

Favorable reactions to list

Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, said the reactions to the checklist have been “overwhelmingly favorable and appreciative.”

Eric J. Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News, tweeted about this list: “For COVID-19, more than ever before, it’s vital to keep clinicians in the U.S. health care workforce. These are 10 steps that will help.” The tweet was retweeted more than 100 times.

Lotte Dyrbye, MD, MHPE, a primary care physician and codirector of the program on physician well-being at the Mayo Clinic in Rochester, Minn., said in an interview that managing the anger around patients who choose to be unvaccinated is critical and something that has gotten little notice since the vaccines became available.

“Physicians and nurses are working extremely hard and seeing a lot of suffering and are taking care of patients very sick with COVID-19, knowing they had access to the vaccine. That is causing anger and frustration. We haven’t prepared health care workers to deal with that,” she said.
 

Outside expert: Not all items may be easy to implement

Dr. Dyrbye said that, though she found adding time to address COVID misinformation questions in appointments is very important, it may be wishful thinking.

The authors suggested training other members of the care team to answer those questions to free up time, but she said, for patients who have been swayed by misinformation, hearing information from someone other than the physician they have a relationship with won’t be convincing.

According to Dr. Dyrbye, the items on the list are not easy to implement, but the action plan is worthwhile to consider adopting as a multipronged approach.

“Most of these things are hard and we need to be in it for the long run,” she said.

The need is clear for efforts to address the mental health of not just experienced clinicians but those in training as well, she noted.
 

Related research

A study that was also recently published in the Annals of Internal Medicine suggested that making a few simple changes can help improve the mental health of residents. The research, which included nearly 17,000 first-year residents who started training between 2007 and 2019, addressed indicators of mental health in light of interventions such as limiting residents’ work hours and providing more services.

The investigators found that, though depression remains high among residents, depressive symptoms among first-year residents dropped 24.4% from 2007 to 2019 in parallel with four main factors: an increase in mental health services; restrictions on work hours for residents; more sleep hours; and higher-quality feedback from faculty.

Dr. Barrett said she hopes her colleagues and health care workers everywhere will find some solace in seeing that the new checklist she coauthored was published in a prominent journal.

The message Dr. Barrett said she hopes they see is: “Someone is validating it is not in their head. They are validating we can do better. They are validating that we must.”

Dr. Barrett and coauthors had no conflicts of interest. Dr. Gold and Dr. Dyrbye also disclosed having no relevant financial relationships.

COVID-19’s relentless toll on the clinical workforce inspired four doctors to draft an action plan to stem the exits and help colleagues preserve their physical and mental health.

Indeed, a recent poll of 1,000 health care workers conducted Sept. 2-8 by Morning Consult, showed that 18% of medical workers polled quit their jobs during the pandemic. Additionally, 31% said they had at least thought about leaving their work.

“As physicians, educators, peers and friends of COVID-19 responders, we are gravely concerned about our colleagues’ exhaustion, burnout, and disillusionment,” wrote lead author Eileen Barrett, MD, and coauthors of the new action plan, which was published in the Annals of Internal Medicine.

The 10-point, one-page checklist includes providing “practical support in the areas that clinicians identify as causing emotional stress or moral injury,” such as managing anger and grief when patients have chosen not to be vaccinated or confronting misinformation.

“Those are the things that are making people’s mental health worse” psychiatrist Jessi Gold, MD, MS, said in an interview. “I don’t think I’ve seen that mentioned other places.”

Among the other action items are:

• Reduce administrative tasks that are not “mission critical,” such as mandatory training that has no evidence of improving patient outcomes and meetings that could be skipped.
• Offer free and confidential resources to support clinicians’ mental health, such as easy access to crisis hotlines and peer support groups.
• Maintain transparency about personal protective equipment and contingency plans when there are shortages to restore trust.
• Encourage clinicians to use vacation time; leaders should model this.
• Implement suicide prevention strategies, including wellness check-ins for clinicians in hard-hit areas.

The action plan was based on the authors’ own experiences and the stories of colleagues and information in literature. It includes 10 changes health care leaders could make to help retain providers who may be on the brink of leaving their jobs or leaving medicine

Action items intended to be easily achievable, low cost

Dr. Barrett, who is a hospitalist in Albuquerque, said the goal was to present easily achievable and low-cost action items that clinicians and health care leaders could use as a starting point when change seems insurmountable and evidence on what works is slow to come.

She said one of the things that spurred her to coauthor the list was becoming aware of other clinicians’ “secret shame” in thinking about leaving medicine.

“Maybe a person who is not being listened to could take this journal article and say ‘we don’t know where to start. It looks like we can start here,’ ” said Dr. Barrett, who is also an associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.

She noted that some of the good ideas floated around did not make the list, because they required daunting budget commitments and too much time to put into place.

Numerous other proposed solutions were of the wrong tone, according to Dr. Barrett.

“It’s not just about a hug or a piece of pizza,” she said.

Dr. Gold, who is an assistant professor at Washington University, St. Louis, and specializes in the mental health of health care workers, noted that, even though the list was pared to 10 action items, it is still hard for health care organizations to prioritize mental health.

“Many hospitals are still struggling with the active bleed of the pandemic and financially recovering,” she said. “If you’re dealing with a full ER and people are still dying of COVID and you don’t have the resources to support them, it’s really hard to then find magic money to deal with mental health. I’d love for that to be true.”

Every organization, however, can start with removing questions about mental and physical health diagnoses from credentialing and employment applications, which is one of the items on the list, she said.

“It’s the lowest-bar thing that you can fix for making people in crisis not fear getting help,” she said. That change must come on a state-by-state and individual hospital level.

Favorable reactions to list

Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, said the reactions to the checklist have been “overwhelmingly favorable and appreciative.”

Eric J. Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News, tweeted about this list: “For COVID-19, more than ever before, it’s vital to keep clinicians in the U.S. health care workforce. These are 10 steps that will help.” The tweet was retweeted more than 100 times.

Lotte Dyrbye, MD, MHPE, a primary care physician and codirector of the program on physician well-being at the Mayo Clinic in Rochester, Minn., said in an interview that managing the anger around patients who choose to be unvaccinated is critical and something that has gotten little notice since the vaccines became available.

“Physicians and nurses are working extremely hard and seeing a lot of suffering and are taking care of patients very sick with COVID-19, knowing they had access to the vaccine. That is causing anger and frustration. We haven’t prepared health care workers to deal with that,” she said.
 

Outside expert: Not all items may be easy to implement

Dr. Dyrbye said that, though she found adding time to address COVID misinformation questions in appointments is very important, it may be wishful thinking.

The authors suggested training other members of the care team to answer those questions to free up time, but she said, for patients who have been swayed by misinformation, hearing information from someone other than the physician they have a relationship with won’t be convincing.

According to Dr. Dyrbye, the items on the list are not easy to implement, but the action plan is worthwhile to consider adopting as a multipronged approach.

“Most of these things are hard and we need to be in it for the long run,” she said.

The need is clear for efforts to address the mental health of not just experienced clinicians but those in training as well, she noted.
 

Related research

A study that was also recently published in the Annals of Internal Medicine suggested that making a few simple changes can help improve the mental health of residents. The research, which included nearly 17,000 first-year residents who started training between 2007 and 2019, addressed indicators of mental health in light of interventions such as limiting residents’ work hours and providing more services.

The investigators found that, though depression remains high among residents, depressive symptoms among first-year residents dropped 24.4% from 2007 to 2019 in parallel with four main factors: an increase in mental health services; restrictions on work hours for residents; more sleep hours; and higher-quality feedback from faculty.

Dr. Barrett said she hopes her colleagues and health care workers everywhere will find some solace in seeing that the new checklist she coauthored was published in a prominent journal.

The message Dr. Barrett said she hopes they see is: “Someone is validating it is not in their head. They are validating we can do better. They are validating that we must.”

Dr. Barrett and coauthors had no conflicts of interest. Dr. Gold and Dr. Dyrbye also disclosed having no relevant financial relationships.

COVID-19’s relentless toll on the clinical workforce inspired four doctors to draft an action plan to stem the exits and help colleagues preserve their physical and mental health.

Indeed, a recent poll of 1,000 health care workers conducted Sept. 2-8 by Morning Consult, showed that 18% of medical workers polled quit their jobs during the pandemic. Additionally, 31% said they had at least thought about leaving their work.

“As physicians, educators, peers and friends of COVID-19 responders, we are gravely concerned about our colleagues’ exhaustion, burnout, and disillusionment,” wrote lead author Eileen Barrett, MD, and coauthors of the new action plan, which was published in the Annals of Internal Medicine.

The 10-point, one-page checklist includes providing “practical support in the areas that clinicians identify as causing emotional stress or moral injury,” such as managing anger and grief when patients have chosen not to be vaccinated or confronting misinformation.

“Those are the things that are making people’s mental health worse” psychiatrist Jessi Gold, MD, MS, said in an interview. “I don’t think I’ve seen that mentioned other places.”

Among the other action items are:

• Reduce administrative tasks that are not “mission critical,” such as mandatory training that has no evidence of improving patient outcomes and meetings that could be skipped.
• Offer free and confidential resources to support clinicians’ mental health, such as easy access to crisis hotlines and peer support groups.
• Maintain transparency about personal protective equipment and contingency plans when there are shortages to restore trust.
• Encourage clinicians to use vacation time; leaders should model this.
• Implement suicide prevention strategies, including wellness check-ins for clinicians in hard-hit areas.

The action plan was based on the authors’ own experiences and the stories of colleagues and information in literature. It includes 10 changes health care leaders could make to help retain providers who may be on the brink of leaving their jobs or leaving medicine

Action items intended to be easily achievable, low cost

Dr. Barrett, who is a hospitalist in Albuquerque, said the goal was to present easily achievable and low-cost action items that clinicians and health care leaders could use as a starting point when change seems insurmountable and evidence on what works is slow to come.

She said one of the things that spurred her to coauthor the list was becoming aware of other clinicians’ “secret shame” in thinking about leaving medicine.

“Maybe a person who is not being listened to could take this journal article and say ‘we don’t know where to start. It looks like we can start here,’ ” said Dr. Barrett, who is also an associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.

She noted that some of the good ideas floated around did not make the list, because they required daunting budget commitments and too much time to put into place.

Numerous other proposed solutions were of the wrong tone, according to Dr. Barrett.

“It’s not just about a hug or a piece of pizza,” she said.

Dr. Gold, who is an assistant professor at Washington University, St. Louis, and specializes in the mental health of health care workers, noted that, even though the list was pared to 10 action items, it is still hard for health care organizations to prioritize mental health.

“Many hospitals are still struggling with the active bleed of the pandemic and financially recovering,” she said. “If you’re dealing with a full ER and people are still dying of COVID and you don’t have the resources to support them, it’s really hard to then find magic money to deal with mental health. I’d love for that to be true.”

Every organization, however, can start with removing questions about mental and physical health diagnoses from credentialing and employment applications, which is one of the items on the list, she said.

“It’s the lowest-bar thing that you can fix for making people in crisis not fear getting help,” she said. That change must come on a state-by-state and individual hospital level.

Favorable reactions to list

Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, said the reactions to the checklist have been “overwhelmingly favorable and appreciative.”

Eric J. Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News, tweeted about this list: “For COVID-19, more than ever before, it’s vital to keep clinicians in the U.S. health care workforce. These are 10 steps that will help.” The tweet was retweeted more than 100 times.

Lotte Dyrbye, MD, MHPE, a primary care physician and codirector of the program on physician well-being at the Mayo Clinic in Rochester, Minn., said in an interview that managing the anger around patients who choose to be unvaccinated is critical and something that has gotten little notice since the vaccines became available.

“Physicians and nurses are working extremely hard and seeing a lot of suffering and are taking care of patients very sick with COVID-19, knowing they had access to the vaccine. That is causing anger and frustration. We haven’t prepared health care workers to deal with that,” she said.
 

Outside expert: Not all items may be easy to implement

Dr. Dyrbye said that, though she found adding time to address COVID misinformation questions in appointments is very important, it may be wishful thinking.

The authors suggested training other members of the care team to answer those questions to free up time, but she said, for patients who have been swayed by misinformation, hearing information from someone other than the physician they have a relationship with won’t be convincing.

According to Dr. Dyrbye, the items on the list are not easy to implement, but the action plan is worthwhile to consider adopting as a multipronged approach.

“Most of these things are hard and we need to be in it for the long run,” she said.

The need is clear for efforts to address the mental health of not just experienced clinicians but those in training as well, she noted.
 

Related research

A study that was also recently published in the Annals of Internal Medicine suggested that making a few simple changes can help improve the mental health of residents. The research, which included nearly 17,000 first-year residents who started training between 2007 and 2019, addressed indicators of mental health in light of interventions such as limiting residents’ work hours and providing more services.

The investigators found that, though depression remains high among residents, depressive symptoms among first-year residents dropped 24.4% from 2007 to 2019 in parallel with four main factors: an increase in mental health services; restrictions on work hours for residents; more sleep hours; and higher-quality feedback from faculty.

Dr. Barrett said she hopes her colleagues and health care workers everywhere will find some solace in seeing that the new checklist she coauthored was published in a prominent journal.

The message Dr. Barrett said she hopes they see is: “Someone is validating it is not in their head. They are validating we can do better. They are validating that we must.”

Dr. Barrett and coauthors had no conflicts of interest. Dr. Gold and Dr. Dyrbye also disclosed having no relevant financial relationships.

A second U.S. case of COVID-19 caused by the Omicron variant has been picked up by genetic testing in Minnesota.

The man, from Hennepin County, Minn., fell ill on Nov. 22 after attending the Anime NYC 2021 conference at the Javits Center in New York City a few days before.  He sought testing on Nov. 24.  His symptoms have resolved, according to a press release on the case from the Minnesota Department of Health.  The man was fully vaccinated, the department said.

He was advised to isolate from others, but it’s unclear if he had contact with anyone else before he learning he was infected.

“This news is concerning, but it is not a surprise,” said Governor Tim Walz in a news release. “We know that this virus is highly infectious and moves quickly throughout the world. Minnesotans know what to do to keep each other safe now — get the vaccine, get tested, wear a mask indoors, and get a booster. Together, we can fight this virus and help keep Minnesotans safe,”

The first case of COVID-19 caused by Omicron was detected Dec. 1 in California. That case was in a traveler who had recently returned from South Africa.

This breaking news story will be updated.

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

A second U.S. case of COVID-19 caused by the Omicron variant has been picked up by genetic testing in Minnesota.

The man, from Hennepin County, Minn., fell ill on Nov. 22 after attending the Anime NYC 2021 conference at the Javits Center in New York City a few days before.  He sought testing on Nov. 24.  His symptoms have resolved, according to a press release on the case from the Minnesota Department of Health.  The man was fully vaccinated, the department said.

He was advised to isolate from others, but it’s unclear if he had contact with anyone else before he learning he was infected.

“This news is concerning, but it is not a surprise,” said Governor Tim Walz in a news release. “We know that this virus is highly infectious and moves quickly throughout the world. Minnesotans know what to do to keep each other safe now — get the vaccine, get tested, wear a mask indoors, and get a booster. Together, we can fight this virus and help keep Minnesotans safe,”

The first case of COVID-19 caused by Omicron was detected Dec. 1 in California. That case was in a traveler who had recently returned from South Africa.

This breaking news story will be updated.

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

A second U.S. case of COVID-19 caused by the Omicron variant has been picked up by genetic testing in Minnesota.

The man, from Hennepin County, Minn., fell ill on Nov. 22 after attending the Anime NYC 2021 conference at the Javits Center in New York City a few days before.  He sought testing on Nov. 24.  His symptoms have resolved, according to a press release on the case from the Minnesota Department of Health.  The man was fully vaccinated, the department said.

He was advised to isolate from others, but it’s unclear if he had contact with anyone else before he learning he was infected.

“This news is concerning, but it is not a surprise,” said Governor Tim Walz in a news release. “We know that this virus is highly infectious and moves quickly throughout the world. Minnesotans know what to do to keep each other safe now — get the vaccine, get tested, wear a mask indoors, and get a booster. Together, we can fight this virus and help keep Minnesotans safe,”

The first case of COVID-19 caused by Omicron was detected Dec. 1 in California. That case was in a traveler who had recently returned from South Africa.

This breaking news story will be updated.

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

Children diagnosed with type 2 diabetes (T2D) appear significantly more likely to develop retinopathy and other ocular complications over time than children who are diagnosed with type 1 diabetes (T1D), researchers report.

Among a population-based cohort of children (defined as younger than 22 years), the risk of diabetic retinopathy was 88% greater in those with T2D than T1D within the first 15 years of disease diagnosis.

“The purpose of this study was to assess the risk of developing diabetes-associated ocular complications among a population-based cohort of children diagnosed with either T1D or T2D during a 50-year period,” lead author Patricia Bai, BA, of Mayo Clinic, Phoenix, and colleagues reported in JAMA Ophthalmology.

The researchers retrospectively reviewed medical records from all residents of Olmsted County, Minn., from 1970 to 2019. The study cohort included 606 children with a confirmed a diagnosis of T1D or T2D, 525 (87%) of whom had at least one ocular examination.

The mean age at diabetes diagnosis was 12 years (standard deviation, 5.4 years); most participants were White (95.7% in 1990), and half (50%) were male. Diabetes-associated ocular complications occurred in 31.9% and 26.6% of children with T1D and T2D, respectively.

The hazard ratios illustrating the risk between T2D and T1D rates were 1.88 (95% confidence interval, 1.13-3.12; P = .02) for any diabetic retinopathy, 2.33 (95% CI, 0.99-5.50; P = .048) for proliferative diabetic retinopathy, 1.49 (95% CI, 0.46-4.89; P = .50) for diabetic macular edema, 2.43 (95% CI, 0.54-11.07; P = .24) for a visually significant cataract, and 4.06 (95% CI, 1.34-12.33; P = .007) for requiring pars plana vitrectomy within the first 15 years of diagnosis.

These results suggest that earlier surveillance and intervention may help prevent vision-threatening complications, the researchers explained.

“After adjusting for race using self-identified categories of White or not White, the adjusted HR of developing any retinopathy was 1.63 (95% CI, 0.96-2.79; P = .07), and the adjusted HR of developing proliferative diabetic retinopathy was 2.02 (95% CI, 0.79-5.16; P = .14)” in T2D versus T1D patients, the researchers wrote.

“We would expect the reported rate of type 2 diabetes to be potentially underestimated in our study cohort,” Ms. Bai commented in an interview. “Race has been suggested to be a surrogate for other social determinants of health, such as lower rates of optimal follow-up care received by racial and ethnic minorities, which could influence subsequent retinopathy rates.”
 

Understanding retinopathy outcomes in youth

In an accompanying editorial, Jennifer K. Sun, MD, MPH, from Harvard Medical School, Boston, wrote that the present study indicates the natural history of retinopathy may differ between patients with T1D and T2D.

While the pathophysiology of diabetic retinopathy in T1D and T2D appears similar, other patient-related factors such as lipid profiles, the presence of hypertension, and body mass index may differ between the two disease states.

She wrote that “there is a particular need to document retinopathy outcomes and risk factors for advanced disease in youth with T2D, for whom there is a paucity of information.”

Ms. Bai and colleagues acknowledged that a key limitation of the study was the retrospective design. As a result, irregular follow-up and incomplete data may limit the applicability of the findings.

“Some children with milder forms of diabetes may have eluded detection, a limitation that is more likely to affect T2D, which may exist undetected for years before a diagnosis,” Bai explained.

Dr. Sun recommended that further epidemiologic studies are needed to help optimize guidelines for screening and follow-up for young people diagnosed with diabetes. “Such efforts may potentially lead to increased understanding of the mechanistic differences between pathology in T1D versus T2D,” she concluded.

This study used the resources of the Rochester Epidemiology Project (REP) medical records linkage system, which is supported by grant funding from the National Institute on Aging, the Mayo Clinic Research Committee, and by fees paid annually by REP users. The study authors disclosed no conflicts of interest.

Children diagnosed with type 2 diabetes (T2D) appear significantly more likely to develop retinopathy and other ocular complications over time than children who are diagnosed with type 1 diabetes (T1D), researchers report.

Among a population-based cohort of children (defined as younger than 22 years), the risk of diabetic retinopathy was 88% greater in those with T2D than T1D within the first 15 years of disease diagnosis.

“The purpose of this study was to assess the risk of developing diabetes-associated ocular complications among a population-based cohort of children diagnosed with either T1D or T2D during a 50-year period,” lead author Patricia Bai, BA, of Mayo Clinic, Phoenix, and colleagues reported in JAMA Ophthalmology.

The researchers retrospectively reviewed medical records from all residents of Olmsted County, Minn., from 1970 to 2019. The study cohort included 606 children with a confirmed a diagnosis of T1D or T2D, 525 (87%) of whom had at least one ocular examination.

The mean age at diabetes diagnosis was 12 years (standard deviation, 5.4 years); most participants were White (95.7% in 1990), and half (50%) were male. Diabetes-associated ocular complications occurred in 31.9% and 26.6% of children with T1D and T2D, respectively.

The hazard ratios illustrating the risk between T2D and T1D rates were 1.88 (95% confidence interval, 1.13-3.12; P = .02) for any diabetic retinopathy, 2.33 (95% CI, 0.99-5.50; P = .048) for proliferative diabetic retinopathy, 1.49 (95% CI, 0.46-4.89; P = .50) for diabetic macular edema, 2.43 (95% CI, 0.54-11.07; P = .24) for a visually significant cataract, and 4.06 (95% CI, 1.34-12.33; P = .007) for requiring pars plana vitrectomy within the first 15 years of diagnosis.

These results suggest that earlier surveillance and intervention may help prevent vision-threatening complications, the researchers explained.

“After adjusting for race using self-identified categories of White or not White, the adjusted HR of developing any retinopathy was 1.63 (95% CI, 0.96-2.79; P = .07), and the adjusted HR of developing proliferative diabetic retinopathy was 2.02 (95% CI, 0.79-5.16; P = .14)” in T2D versus T1D patients, the researchers wrote.

“We would expect the reported rate of type 2 diabetes to be potentially underestimated in our study cohort,” Ms. Bai commented in an interview. “Race has been suggested to be a surrogate for other social determinants of health, such as lower rates of optimal follow-up care received by racial and ethnic minorities, which could influence subsequent retinopathy rates.”
 

Understanding retinopathy outcomes in youth

In an accompanying editorial, Jennifer K. Sun, MD, MPH, from Harvard Medical School, Boston, wrote that the present study indicates the natural history of retinopathy may differ between patients with T1D and T2D.

While the pathophysiology of diabetic retinopathy in T1D and T2D appears similar, other patient-related factors such as lipid profiles, the presence of hypertension, and body mass index may differ between the two disease states.

She wrote that “there is a particular need to document retinopathy outcomes and risk factors for advanced disease in youth with T2D, for whom there is a paucity of information.”

Ms. Bai and colleagues acknowledged that a key limitation of the study was the retrospective design. As a result, irregular follow-up and incomplete data may limit the applicability of the findings.

“Some children with milder forms of diabetes may have eluded detection, a limitation that is more likely to affect T2D, which may exist undetected for years before a diagnosis,” Bai explained.

Dr. Sun recommended that further epidemiologic studies are needed to help optimize guidelines for screening and follow-up for young people diagnosed with diabetes. “Such efforts may potentially lead to increased understanding of the mechanistic differences between pathology in T1D versus T2D,” she concluded.

This study used the resources of the Rochester Epidemiology Project (REP) medical records linkage system, which is supported by grant funding from the National Institute on Aging, the Mayo Clinic Research Committee, and by fees paid annually by REP users. The study authors disclosed no conflicts of interest.

Children diagnosed with type 2 diabetes (T2D) appear significantly more likely to develop retinopathy and other ocular complications over time than children who are diagnosed with type 1 diabetes (T1D), researchers report.

Among a population-based cohort of children (defined as younger than 22 years), the risk of diabetic retinopathy was 88% greater in those with T2D than T1D within the first 15 years of disease diagnosis.

“The purpose of this study was to assess the risk of developing diabetes-associated ocular complications among a population-based cohort of children diagnosed with either T1D or T2D during a 50-year period,” lead author Patricia Bai, BA, of Mayo Clinic, Phoenix, and colleagues reported in JAMA Ophthalmology.

The researchers retrospectively reviewed medical records from all residents of Olmsted County, Minn., from 1970 to 2019. The study cohort included 606 children with a confirmed a diagnosis of T1D or T2D, 525 (87%) of whom had at least one ocular examination.

The mean age at diabetes diagnosis was 12 years (standard deviation, 5.4 years); most participants were White (95.7% in 1990), and half (50%) were male. Diabetes-associated ocular complications occurred in 31.9% and 26.6% of children with T1D and T2D, respectively.

The hazard ratios illustrating the risk between T2D and T1D rates were 1.88 (95% confidence interval, 1.13-3.12; P = .02) for any diabetic retinopathy, 2.33 (95% CI, 0.99-5.50; P = .048) for proliferative diabetic retinopathy, 1.49 (95% CI, 0.46-4.89; P = .50) for diabetic macular edema, 2.43 (95% CI, 0.54-11.07; P = .24) for a visually significant cataract, and 4.06 (95% CI, 1.34-12.33; P = .007) for requiring pars plana vitrectomy within the first 15 years of diagnosis.

These results suggest that earlier surveillance and intervention may help prevent vision-threatening complications, the researchers explained.

“After adjusting for race using self-identified categories of White or not White, the adjusted HR of developing any retinopathy was 1.63 (95% CI, 0.96-2.79; P = .07), and the adjusted HR of developing proliferative diabetic retinopathy was 2.02 (95% CI, 0.79-5.16; P = .14)” in T2D versus T1D patients, the researchers wrote.

“We would expect the reported rate of type 2 diabetes to be potentially underestimated in our study cohort,” Ms. Bai commented in an interview. “Race has been suggested to be a surrogate for other social determinants of health, such as lower rates of optimal follow-up care received by racial and ethnic minorities, which could influence subsequent retinopathy rates.”
 

Understanding retinopathy outcomes in youth

In an accompanying editorial, Jennifer K. Sun, MD, MPH, from Harvard Medical School, Boston, wrote that the present study indicates the natural history of retinopathy may differ between patients with T1D and T2D.

While the pathophysiology of diabetic retinopathy in T1D and T2D appears similar, other patient-related factors such as lipid profiles, the presence of hypertension, and body mass index may differ between the two disease states.

She wrote that “there is a particular need to document retinopathy outcomes and risk factors for advanced disease in youth with T2D, for whom there is a paucity of information.”

Ms. Bai and colleagues acknowledged that a key limitation of the study was the retrospective design. As a result, irregular follow-up and incomplete data may limit the applicability of the findings.

“Some children with milder forms of diabetes may have eluded detection, a limitation that is more likely to affect T2D, which may exist undetected for years before a diagnosis,” Bai explained.

Dr. Sun recommended that further epidemiologic studies are needed to help optimize guidelines for screening and follow-up for young people diagnosed with diabetes. “Such efforts may potentially lead to increased understanding of the mechanistic differences between pathology in T1D versus T2D,” she concluded.

This study used the resources of the Rochester Epidemiology Project (REP) medical records linkage system, which is supported by grant funding from the National Institute on Aging, the Mayo Clinic Research Committee, and by fees paid annually by REP users. The study authors disclosed no conflicts of interest.

Physical activity levels may decline during major life events, and it’s important for health care professionals to encourage patients to maintain regular physical activity during times of significant changes in their lives, the American Heart Association says in a new scientific statement.

With this statement, “We hope health care providers, public health workers, and individuals understand that a major life change can lead to decreases in physical activity or increases in sedentary behavior,” writing group chair Abbi D. Lane-Cordova, PhD, said in an interview.

The statement includes “tips for screening for physical activity and talking to people about their activity during these big life events and resources that can be used by health care providers to help people achieve healthy levels of physical activity,” said Dr. Lane-Cordova, assistant professor in exercise science, Arnold School of Public Health, University of South Carolina, Columbia.

The statement was published online Dec. 1 in the journal Circulation.

The AHA Committee on Physical Activity, part of the organization’s Council on Lifestyle and Cardiometabolic Health, began discussing this topic back in 2019, Dr. Lane-Cordova explained.

“We spoke as a group about how much activity levels can change when something big happens in life, like becoming a parent or retiring. The change in activity behavior (physical activity or sedentary behavior) is important because these activity behaviors can influence heart health,” she said.

The group started work on the scientific statement in early 2020 – “and then the pandemic hit, and it seemed more important than ever to create awareness and a resource for people to help improve, or at least maintain, favorable activity behaviors when there’s a profound change or event in life,” Dr. Lane-Cordova said.
 

Some more vulnerable than others

The writing group examined data on 17 different life events or transitions and found evidence that physical activity levels may decline during nine events: beginning a new school (elementary, middle, high school, or college); a first job or career change; a marriage or civil union; pregnancy; parenting; retirement; or moving into a long-term care facility.

The authors also identified individuals who may be particularly susceptible to lower levels of physical activity in general and during important life events. They include those with lower levels of education; those who live alone; those who lack access to a safe outdoor space; Black Americans; some members of the LGBTQ+ community; and women who are pregnant and new parents.

They offer practical strategies for health care professionals to support routine physical activity levels during major life events and transitions. These include asking simple questions about how life transitions may be changing physical activity patterns and encouraging the use of wearable step trackers to monitor levels and changes.

“It’s important to maintain or improve physical activity when major life events happen, which is often a time when exercise is most needed,” Dr. Lane-Cordova said in a news release.

“Clinicians should express compassion as they ask about life transitions and initiate conversations about physical activity during life events and transitions,” the writing group advises.

The group also says its important “to look beyond the health care setting and engage organizations, communities, workplaces, faith-based communities, and assisted living facilities to promote physical activity.”

The statement provides a list of resources for individuals and health care professionals, many of which are free and online.

This research had no commercial funding. Members of the writing group have disclosed no relevant financial relationships.

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

Physical activity levels may decline during major life events, and it’s important for health care professionals to encourage patients to maintain regular physical activity during times of significant changes in their lives, the American Heart Association says in a new scientific statement.

With this statement, “We hope health care providers, public health workers, and individuals understand that a major life change can lead to decreases in physical activity or increases in sedentary behavior,” writing group chair Abbi D. Lane-Cordova, PhD, said in an interview.

The statement includes “tips for screening for physical activity and talking to people about their activity during these big life events and resources that can be used by health care providers to help people achieve healthy levels of physical activity,” said Dr. Lane-Cordova, assistant professor in exercise science, Arnold School of Public Health, University of South Carolina, Columbia.

The statement was published online Dec. 1 in the journal Circulation.

The AHA Committee on Physical Activity, part of the organization’s Council on Lifestyle and Cardiometabolic Health, began discussing this topic back in 2019, Dr. Lane-Cordova explained.

“We spoke as a group about how much activity levels can change when something big happens in life, like becoming a parent or retiring. The change in activity behavior (physical activity or sedentary behavior) is important because these activity behaviors can influence heart health,” she said.

The group started work on the scientific statement in early 2020 – “and then the pandemic hit, and it seemed more important than ever to create awareness and a resource for people to help improve, or at least maintain, favorable activity behaviors when there’s a profound change or event in life,” Dr. Lane-Cordova said.
 

Some more vulnerable than others

The writing group examined data on 17 different life events or transitions and found evidence that physical activity levels may decline during nine events: beginning a new school (elementary, middle, high school, or college); a first job or career change; a marriage or civil union; pregnancy; parenting; retirement; or moving into a long-term care facility.

The authors also identified individuals who may be particularly susceptible to lower levels of physical activity in general and during important life events. They include those with lower levels of education; those who live alone; those who lack access to a safe outdoor space; Black Americans; some members of the LGBTQ+ community; and women who are pregnant and new parents.

They offer practical strategies for health care professionals to support routine physical activity levels during major life events and transitions. These include asking simple questions about how life transitions may be changing physical activity patterns and encouraging the use of wearable step trackers to monitor levels and changes.

“It’s important to maintain or improve physical activity when major life events happen, which is often a time when exercise is most needed,” Dr. Lane-Cordova said in a news release.

“Clinicians should express compassion as they ask about life transitions and initiate conversations about physical activity during life events and transitions,” the writing group advises.

The group also says its important “to look beyond the health care setting and engage organizations, communities, workplaces, faith-based communities, and assisted living facilities to promote physical activity.”

The statement provides a list of resources for individuals and health care professionals, many of which are free and online.

This research had no commercial funding. Members of the writing group have disclosed no relevant financial relationships.

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

Physical activity levels may decline during major life events, and it’s important for health care professionals to encourage patients to maintain regular physical activity during times of significant changes in their lives, the American Heart Association says in a new scientific statement.

With this statement, “We hope health care providers, public health workers, and individuals understand that a major life change can lead to decreases in physical activity or increases in sedentary behavior,” writing group chair Abbi D. Lane-Cordova, PhD, said in an interview.

The statement includes “tips for screening for physical activity and talking to people about their activity during these big life events and resources that can be used by health care providers to help people achieve healthy levels of physical activity,” said Dr. Lane-Cordova, assistant professor in exercise science, Arnold School of Public Health, University of South Carolina, Columbia.

The statement was published online Dec. 1 in the journal Circulation.

The AHA Committee on Physical Activity, part of the organization’s Council on Lifestyle and Cardiometabolic Health, began discussing this topic back in 2019, Dr. Lane-Cordova explained.

“We spoke as a group about how much activity levels can change when something big happens in life, like becoming a parent or retiring. The change in activity behavior (physical activity or sedentary behavior) is important because these activity behaviors can influence heart health,” she said.

The group started work on the scientific statement in early 2020 – “and then the pandemic hit, and it seemed more important than ever to create awareness and a resource for people to help improve, or at least maintain, favorable activity behaviors when there’s a profound change or event in life,” Dr. Lane-Cordova said.
 

Some more vulnerable than others

The writing group examined data on 17 different life events or transitions and found evidence that physical activity levels may decline during nine events: beginning a new school (elementary, middle, high school, or college); a first job or career change; a marriage or civil union; pregnancy; parenting; retirement; or moving into a long-term care facility.

The authors also identified individuals who may be particularly susceptible to lower levels of physical activity in general and during important life events. They include those with lower levels of education; those who live alone; those who lack access to a safe outdoor space; Black Americans; some members of the LGBTQ+ community; and women who are pregnant and new parents.

They offer practical strategies for health care professionals to support routine physical activity levels during major life events and transitions. These include asking simple questions about how life transitions may be changing physical activity patterns and encouraging the use of wearable step trackers to monitor levels and changes.

“It’s important to maintain or improve physical activity when major life events happen, which is often a time when exercise is most needed,” Dr. Lane-Cordova said in a news release.

“Clinicians should express compassion as they ask about life transitions and initiate conversations about physical activity during life events and transitions,” the writing group advises.

The group also says its important “to look beyond the health care setting and engage organizations, communities, workplaces, faith-based communities, and assisted living facilities to promote physical activity.”

The statement provides a list of resources for individuals and health care professionals, many of which are free and online.

This research had no commercial funding. Members of the writing group have disclosed no relevant financial relationships.

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

It isn’t autocorrect’s fault this time, we swear

We’ve come a long way with communication technology. Back in the day, when Gondor needed to call for aid, they had to pull off the greatest signal fire montage of all time. Now we can send each other texts back and forth in an instant. (“Hey Theoden, send army, need help pls” doesn’t quite have the same gravitas though.) The question is, how do our brains keep up with such rapidly advancing technology?

Deagreez/iStock/Getty Images Plus

Er, they don’t. Not really. Instead, our brains create shortcuts called “good-enough language processing,” which is exactly what it sounds like.

Psychologists and psycholinguists have been studying misinterpretations such as good-enough language processing since the 1970s. Recently, however, psycholinguists from the Centre for Language and Brain at Higher School of Economics in Moscow have found that, when it comes to reading comprehension over text, older adults are using their knowledge of the world over how it’s grammatically formed in the sentence.

In the study, 349 people were asked to read and interpret four sentences, the third of which (translated from Russian) was: “Misha met the firefighter’s dentist, who had put out a fire in the warehouse.” When asked who put the fire out, 79% of older adults (aged 55 years and older), utilizing good-enough language processing, said the firefighter put out the fire. You probably glossed over that sentence and assumed the same thing. But this time, the dentist was the real hero.

That said, adolescents (aged 13-17) and young adults (aged 20-30) weren’t much better, and got that particular sentence wrong 63%-68% of the time. According to the researchers, good-enough language processing forms in adolescence and intensifies throughout adulthood.

Moral of the story? We should utilize signal fires more often. Less room for misinterpretation. When the beacons of Minas Tirith were lit, Rohan answered.
 

Singing … your … lungs … out

There’s nothing quite like a karaoke bar to unleash your inner rock star. Hey, why not just go for it, everyone is just as bad at singing as you. That’s part of the fun.

lisegagne/E+/Getty Images

A 25-year-old man named Wang Zhe may have taken the karaoke concept a bit too far, however. While out with friends at a birthday party, Mr. Zhe let loose on a song with a particularly large number of high notes. He tried his best, gamely attacking the song until he felt a pain in his chest. He didn’t think much of it, although he did cut his performance short, but then he awoke the next morning unable to breathe properly.

After a trip to the hospital, he explained the sequence of events to the doctors, and an x-ray found that the culprit of the pain and difficulty breathing was a life-threatening condition in which air bubbles are created between the chest and lung. All the force Mr. Zhe had used trying to sing made air sacks in his lung burst, causing the air bubbles and his lung to be compressed to 15% of what it should be. Mr. Zhe needed surgery to remove the air bubbles, but fortunately turned out just fine.

So, if you’re ever at a karaoke bar, looking for a song to sing, maybe avoid the ones with super high notes and stick with something a little lower. We’re picturing something like Paul Robeson singing Ol’ Man River. That oughta do the trick.
 

And the word of the year is …

Flibbertigibbet. Bamboozle. Gobbledygook. If the LOTME staff had any say, those would be the words of the year every year, but sadly, we’re not in charge of such things. Instead, we’ll just have to defer to Oxford and Merriam-Webster, both of whom have recently chosen their words of the year. No word yet on whether or not they made their announcement at a red carpet gala dinner attended by all the most fashionable and powerful words out there, but we’re hoping that’s what happened.

NoSystem images/Getty Images

We’ll start with Oxford, since they did choose first. We all know Oxford is the bad boy of the dictionary world, so they’ve chosen a casual colloquialism related to the big COVID-sized elephant in the room (or should it be elephant-sized COVID in the room?): Vax. According to them, while vax has been hanging around since the 1980s, it’s only been in the past year that it’s exploded in popularity in a wide range of contexts (we can’t imagine what those would be). According to Oxford, “as a short pithy word, it appeals, perhaps especially to media commentators, when more formal alternatives are much more long-winded.”

Speaking of long-winded, that brings us to Merriam-Webster, the sheltered nerd of the dictionary world. Clearly they’re too good for vax, so they’ve gone with vaccine as their 2021 word of the year. Vaccine, according to Merriam-Webster, carries two big stories: The impressive and herculean feat of bringing a COVID-19 vaccine so quickly to so many people, and the complex political and social upheaval between vaccine supporters and deniers.

Vaccine also serves as a great bookend for Merriam-Webster’s 2020 word of the year: Pandemic. In 2020, the pandemic started, and in 2021, thanks to the vaccine, the pandemic ends. That’s how it works, right? We have a vaccine, it’s all over now. What’s that? Omicron? No! Bad COVID! You do that outside, not on the carpet!

It isn’t autocorrect’s fault this time, we swear

We’ve come a long way with communication technology. Back in the day, when Gondor needed to call for aid, they had to pull off the greatest signal fire montage of all time. Now we can send each other texts back and forth in an instant. (“Hey Theoden, send army, need help pls” doesn’t quite have the same gravitas though.) The question is, how do our brains keep up with such rapidly advancing technology?

Deagreez/iStock/Getty Images Plus

Er, they don’t. Not really. Instead, our brains create shortcuts called “good-enough language processing,” which is exactly what it sounds like.

Psychologists and psycholinguists have been studying misinterpretations such as good-enough language processing since the 1970s. Recently, however, psycholinguists from the Centre for Language and Brain at Higher School of Economics in Moscow have found that, when it comes to reading comprehension over text, older adults are using their knowledge of the world over how it’s grammatically formed in the sentence.

In the study, 349 people were asked to read and interpret four sentences, the third of which (translated from Russian) was: “Misha met the firefighter’s dentist, who had put out a fire in the warehouse.” When asked who put the fire out, 79% of older adults (aged 55 years and older), utilizing good-enough language processing, said the firefighter put out the fire. You probably glossed over that sentence and assumed the same thing. But this time, the dentist was the real hero.

That said, adolescents (aged 13-17) and young adults (aged 20-30) weren’t much better, and got that particular sentence wrong 63%-68% of the time. According to the researchers, good-enough language processing forms in adolescence and intensifies throughout adulthood.

Moral of the story? We should utilize signal fires more often. Less room for misinterpretation. When the beacons of Minas Tirith were lit, Rohan answered.
 

Singing … your … lungs … out

There’s nothing quite like a karaoke bar to unleash your inner rock star. Hey, why not just go for it, everyone is just as bad at singing as you. That’s part of the fun.

lisegagne/E+/Getty Images

A 25-year-old man named Wang Zhe may have taken the karaoke concept a bit too far, however. While out with friends at a birthday party, Mr. Zhe let loose on a song with a particularly large number of high notes. He tried his best, gamely attacking the song until he felt a pain in his chest. He didn’t think much of it, although he did cut his performance short, but then he awoke the next morning unable to breathe properly.

After a trip to the hospital, he explained the sequence of events to the doctors, and an x-ray found that the culprit of the pain and difficulty breathing was a life-threatening condition in which air bubbles are created between the chest and lung. All the force Mr. Zhe had used trying to sing made air sacks in his lung burst, causing the air bubbles and his lung to be compressed to 15% of what it should be. Mr. Zhe needed surgery to remove the air bubbles, but fortunately turned out just fine.

So, if you’re ever at a karaoke bar, looking for a song to sing, maybe avoid the ones with super high notes and stick with something a little lower. We’re picturing something like Paul Robeson singing Ol’ Man River. That oughta do the trick.
 

And the word of the year is …

Flibbertigibbet. Bamboozle. Gobbledygook. If the LOTME staff had any say, those would be the words of the year every year, but sadly, we’re not in charge of such things. Instead, we’ll just have to defer to Oxford and Merriam-Webster, both of whom have recently chosen their words of the year. No word yet on whether or not they made their announcement at a red carpet gala dinner attended by all the most fashionable and powerful words out there, but we’re hoping that’s what happened.

NoSystem images/Getty Images

We’ll start with Oxford, since they did choose first. We all know Oxford is the bad boy of the dictionary world, so they’ve chosen a casual colloquialism related to the big COVID-sized elephant in the room (or should it be elephant-sized COVID in the room?): Vax. According to them, while vax has been hanging around since the 1980s, it’s only been in the past year that it’s exploded in popularity in a wide range of contexts (we can’t imagine what those would be). According to Oxford, “as a short pithy word, it appeals, perhaps especially to media commentators, when more formal alternatives are much more long-winded.”

Speaking of long-winded, that brings us to Merriam-Webster, the sheltered nerd of the dictionary world. Clearly they’re too good for vax, so they’ve gone with vaccine as their 2021 word of the year. Vaccine, according to Merriam-Webster, carries two big stories: The impressive and herculean feat of bringing a COVID-19 vaccine so quickly to so many people, and the complex political and social upheaval between vaccine supporters and deniers.

Vaccine also serves as a great bookend for Merriam-Webster’s 2020 word of the year: Pandemic. In 2020, the pandemic started, and in 2021, thanks to the vaccine, the pandemic ends. That’s how it works, right? We have a vaccine, it’s all over now. What’s that? Omicron? No! Bad COVID! You do that outside, not on the carpet!

It isn’t autocorrect’s fault this time, we swear

We’ve come a long way with communication technology. Back in the day, when Gondor needed to call for aid, they had to pull off the greatest signal fire montage of all time. Now we can send each other texts back and forth in an instant. (“Hey Theoden, send army, need help pls” doesn’t quite have the same gravitas though.) The question is, how do our brains keep up with such rapidly advancing technology?

Deagreez/iStock/Getty Images Plus

Er, they don’t. Not really. Instead, our brains create shortcuts called “good-enough language processing,” which is exactly what it sounds like.

Psychologists and psycholinguists have been studying misinterpretations such as good-enough language processing since the 1970s. Recently, however, psycholinguists from the Centre for Language and Brain at Higher School of Economics in Moscow have found that, when it comes to reading comprehension over text, older adults are using their knowledge of the world over how it’s grammatically formed in the sentence.

In the study, 349 people were asked to read and interpret four sentences, the third of which (translated from Russian) was: “Misha met the firefighter’s dentist, who had put out a fire in the warehouse.” When asked who put the fire out, 79% of older adults (aged 55 years and older), utilizing good-enough language processing, said the firefighter put out the fire. You probably glossed over that sentence and assumed the same thing. But this time, the dentist was the real hero.

That said, adolescents (aged 13-17) and young adults (aged 20-30) weren’t much better, and got that particular sentence wrong 63%-68% of the time. According to the researchers, good-enough language processing forms in adolescence and intensifies throughout adulthood.

Moral of the story? We should utilize signal fires more often. Less room for misinterpretation. When the beacons of Minas Tirith were lit, Rohan answered.
 

Singing … your … lungs … out

There’s nothing quite like a karaoke bar to unleash your inner rock star. Hey, why not just go for it, everyone is just as bad at singing as you. That’s part of the fun.

lisegagne/E+/Getty Images

A 25-year-old man named Wang Zhe may have taken the karaoke concept a bit too far, however. While out with friends at a birthday party, Mr. Zhe let loose on a song with a particularly large number of high notes. He tried his best, gamely attacking the song until he felt a pain in his chest. He didn’t think much of it, although he did cut his performance short, but then he awoke the next morning unable to breathe properly.

After a trip to the hospital, he explained the sequence of events to the doctors, and an x-ray found that the culprit of the pain and difficulty breathing was a life-threatening condition in which air bubbles are created between the chest and lung. All the force Mr. Zhe had used trying to sing made air sacks in his lung burst, causing the air bubbles and his lung to be compressed to 15% of what it should be. Mr. Zhe needed surgery to remove the air bubbles, but fortunately turned out just fine.

So, if you’re ever at a karaoke bar, looking for a song to sing, maybe avoid the ones with super high notes and stick with something a little lower. We’re picturing something like Paul Robeson singing Ol’ Man River. That oughta do the trick.
 

And the word of the year is …

Flibbertigibbet. Bamboozle. Gobbledygook. If the LOTME staff had any say, those would be the words of the year every year, but sadly, we’re not in charge of such things. Instead, we’ll just have to defer to Oxford and Merriam-Webster, both of whom have recently chosen their words of the year. No word yet on whether or not they made their announcement at a red carpet gala dinner attended by all the most fashionable and powerful words out there, but we’re hoping that’s what happened.

NoSystem images/Getty Images

We’ll start with Oxford, since they did choose first. We all know Oxford is the bad boy of the dictionary world, so they’ve chosen a casual colloquialism related to the big COVID-sized elephant in the room (or should it be elephant-sized COVID in the room?): Vax. According to them, while vax has been hanging around since the 1980s, it’s only been in the past year that it’s exploded in popularity in a wide range of contexts (we can’t imagine what those would be). According to Oxford, “as a short pithy word, it appeals, perhaps especially to media commentators, when more formal alternatives are much more long-winded.”

Speaking of long-winded, that brings us to Merriam-Webster, the sheltered nerd of the dictionary world. Clearly they’re too good for vax, so they’ve gone with vaccine as their 2021 word of the year. Vaccine, according to Merriam-Webster, carries two big stories: The impressive and herculean feat of bringing a COVID-19 vaccine so quickly to so many people, and the complex political and social upheaval between vaccine supporters and deniers.

Vaccine also serves as a great bookend for Merriam-Webster’s 2020 word of the year: Pandemic. In 2020, the pandemic started, and in 2021, thanks to the vaccine, the pandemic ends. That’s how it works, right? We have a vaccine, it’s all over now. What’s that? Omicron? No! Bad COVID! You do that outside, not on the carpet!