You have a will, so you can rest easy, right? Not necessarily. If your will is outdated, it can cause more harm than good. Even though it can provide for some contingencies, an old will can’t cover every change that may have occurred since it was first drawn. Professionals advise that you review your will every few years and more often if situations such as the following five have occurred since you last updated your will.

#1. Family changes
If you’ve had any changes in your family situation, you will probably need to update your will. Events such as marriage, divorce, death, birth, adoption, or a falling out with a loved one may affect how your estate will be distributed, who should act as guardian for your dependents, and who should be named as executor of your estate.

#2. Relocating to a new state
The laws among the states vary. Moving to a new state or purchasing property in another state can affect your estate plan and how property in that state will be taxed and distributed.

#3. Tax law changes
Federal and state legislatures are continually tinkering with federal estate and state inheritance tax laws. An old will may fail to take advantage of strategies that will minimize estate taxes.

#4. You want to support a favorite cause
If you have developed a connection to a cause, you may want to benefit a particular charity with a gift in your estate. Contact us for sample language you can share with your attorney to include a gift to us in your will.

#5. Changes in your estate’s value
When you made your will, your assets may have been relatively modest. Now the value may be larger and your will no longer reflects how you would like your estate divided.

Consider including a gift to the AGA Research Foundation in your will. You will help spark future discoveries in GI. Visit our website at https://gastro.planmylegacy.org or contact us at [email protected].

You have a will, so you can rest easy, right? Not necessarily. If your will is outdated, it can cause more harm than good. Even though it can provide for some contingencies, an old will can’t cover every change that may have occurred since it was first drawn. Professionals advise that you review your will every few years and more often if situations such as the following five have occurred since you last updated your will.

#1. Family changes
If you’ve had any changes in your family situation, you will probably need to update your will. Events such as marriage, divorce, death, birth, adoption, or a falling out with a loved one may affect how your estate will be distributed, who should act as guardian for your dependents, and who should be named as executor of your estate.

#2. Relocating to a new state
The laws among the states vary. Moving to a new state or purchasing property in another state can affect your estate plan and how property in that state will be taxed and distributed.

#3. Tax law changes
Federal and state legislatures are continually tinkering with federal estate and state inheritance tax laws. An old will may fail to take advantage of strategies that will minimize estate taxes.

#4. You want to support a favorite cause
If you have developed a connection to a cause, you may want to benefit a particular charity with a gift in your estate. Contact us for sample language you can share with your attorney to include a gift to us in your will.

#5. Changes in your estate’s value
When you made your will, your assets may have been relatively modest. Now the value may be larger and your will no longer reflects how you would like your estate divided.

Consider including a gift to the AGA Research Foundation in your will. You will help spark future discoveries in GI. Visit our website at https://gastro.planmylegacy.org or contact us at [email protected].

You have a will, so you can rest easy, right? Not necessarily. If your will is outdated, it can cause more harm than good. Even though it can provide for some contingencies, an old will can’t cover every change that may have occurred since it was first drawn. Professionals advise that you review your will every few years and more often if situations such as the following five have occurred since you last updated your will.

#1. Family changes
If you’ve had any changes in your family situation, you will probably need to update your will. Events such as marriage, divorce, death, birth, adoption, or a falling out with a loved one may affect how your estate will be distributed, who should act as guardian for your dependents, and who should be named as executor of your estate.

#2. Relocating to a new state
The laws among the states vary. Moving to a new state or purchasing property in another state can affect your estate plan and how property in that state will be taxed and distributed.

#3. Tax law changes
Federal and state legislatures are continually tinkering with federal estate and state inheritance tax laws. An old will may fail to take advantage of strategies that will minimize estate taxes.

#4. You want to support a favorite cause
If you have developed a connection to a cause, you may want to benefit a particular charity with a gift in your estate. Contact us for sample language you can share with your attorney to include a gift to us in your will.

#5. Changes in your estate’s value
When you made your will, your assets may have been relatively modest. Now the value may be larger and your will no longer reflects how you would like your estate divided.

Consider including a gift to the AGA Research Foundation in your will. You will help spark future discoveries in GI. Visit our website at https://gastro.planmylegacy.org or contact us at [email protected].

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

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

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

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

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

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

Is this the most controversial topic in breast oncology? Quite likely: the results of a recent online poll show split votes and no consensus.

The topic is the use of chemotherapy for premenopausal women with early-stage hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer.

Is the use of chemo in this patient population merely a “graceless” means of achieving ovarian function suppression, as one expert argued in a recent debate?

Or does it offer a distinct cytotoxic benefit, as the other expert countered?

The debate was held during the recent San Antonio Breast Cancer Symposium (SABCS), at which new results were presented that increased the controversy.

The controversy had arisen the previous year over results from the RxPONDER trial.

Five-year follow-up data from RxPONDER showed that adding chemotherapy to endocrine therapy did not improve outcomes over endocrine therapy alone for postmenopausal women with low-risk, node-positive HR+, HER2- breast cancer. This suggests that older women with early-stage breast cancer may safely forgo chemotherapy.

However, the same trial included premenopausal women with the same disease profile, and the results in this subgroup showed that there was benefit from chemotherapy, with a 5-year invasive disease-free survival (IDFS) rate of 94.2%, versus 89.0% for endocrine therapy alone (P = .0004).

The results were immediately controversial.

Some experts suggested the effect was due to the chemotherapy incidentally causing ovarian suppression, not the cytotoxic effect of the drugs on cancer cells. These experts were skeptical about the suggestion that chemotherapy works differently in premenopausal women than it does in postmenopausal women.

Some clinicians feel the lack of clarity creates an opportunity for greater discussion with women when making the treatment decision.

“When I have this conversation with patients, it’s really nuanced,” Stephanie L. Graff, MD, director of breast oncology, Lifespan Cancer Institute, Providence, R.I., told this news organization.

“I would choose chemotherapy for myself, but I’m a chemotherapy doctor, so I’m very comfortable with these medications and their side effects, and I am also very familiar with the slow burn of the side effects of endocrine therapy,” she said.

But for patients who are hearing their options for the first time, the idea of chemotherapy “feels scary,” and there is “a lot of stigma” associated with it, she commented.

Ultimately, she believes in offering patients as much information as possible, inasmuch as “knowledge is power.”

For Dr. Graff, the message from RxPONDER was that, in premenopausal patients with lymph node positive, HR+ breast cancer, “all comers benefited from chemotherapy.”

“And so if the goal is to be maximally aggressive and optimally lower your risk of distant recurrence, which is a life-threatening event, chemotherapy should offered.”

But chemotherapy comes with side effects, so it’s an important conversation to have with patients; RxPONDER showed that the absolute difference in the rate of distant recurrence with chemotherapy was relatively minor, she added.
 

Debate rages on

The debate at SABCS was moderated by Harold J. Burstein, MD, PhD, from the Dana-Farber Cancer Institute, Boston, who commented that if this was “a compelling question last week in clinic, it has now become red hot.”

At the meeting, held in December 2021, new longer-term data from the SOFT and TEXT clinical trials were presented, showing that ovarian suppression with tamoxifen plus an aromatase inhibitor provides a greater reduction in long-term risk of recurrence than tamoxifen alone.

Moreover, updated results from RxPONDER presented at the same session revealed that chemoendocrine therapy was associated with longer IDFS and distant relapse-free survival than endocrine therapy alone for women with one to three positive lymph nodes and a recurrence score of 25 or lower on the Oncotype DX (Genomic Health) 21-gene breast cancer assay.

Dr. Burstein said the debate over the use of chemotherapy in premenopausal women “is the most interesting question right now in early-stage breast cancer.”

The debate focused on the effect of chemotherapy in these patients – was it all down to ovarian function suppression?

Yes, argued Michael Gnant, MD, from the Medical University of Vienna.

Data from “modern adjuvant chemotherapy trials” suggest that chemo offers a 2%-3% benefit in distant disease-free survival at 5 years for premenopausal women, he noted. But the effect is much larger with ovarian function suppression via endocrine therapy, which provides 5-year disease-free and overall survival benefits of 9%-13%.

Older studies have shown that the benefit with chemotherapy is seen only in women who experience amenorrhea with the cytotoxic drugs, Dr. Gnant noted.

“In short, if you give adjuvant chemotherapy and you induce amenorrhea, then there is going to be a survival difference,” he said. “But if you give adjuvant chemotherapy and there is no amenorrhea, there won’t be an outcome difference.”

The ABSCG-05 trial, which compared endocrine therapy with chemotherapy, showed that “in the presence of optimal endocrine adjuvant treatment, adjuvant chemotherapy doesn’t add anything, because you have already achieved the effect of treatment-induced amenorrhea.”

So Dr. Gnant argued that the effect of chemotherapy in RxPONDER was due to ovarian function suppression.

But the real question is: “What does it mean for clinical practice?”

Dr. Gnant asserted that for the “large group of lower-risk premenopausal patients, tamoxifen will be good enough,” while those at moderate or intermediate risk should receive ovarian function suppression with either tamoxifen or an aromatase inhibitor, with the choice dictated by their adverse effects.

Chemotherapy “is just a graceless method of ovarian function suppression and should only be given to high-risk patients and to patients with endocrine nonresponsive disease,” he argued.

On the other side of the debate, Sibylle Loibl, MD, PhD, from the Centre of Hematology and Oncology, Bethanien, Frankfurt, argued that the effect is not all due to ovarian function suppression and that chemotherapy also has a cytotoxic effect in these patients.

“We need chemotherapy” because “cancer in young women is biologically different,” she asserted.

Dr. Loibl pointed to data currently awaiting publication in the Journal of the National Cancer Institute that suggest that younger women have “higher immune gene expression” that may make them more chemotherapy sensitive, and lower expression of hormone receptor genes, which “could make them less endocrine sensitive.”

She also cited data from a study from her own group that showed that pathologic complete response rates to neoadjuvant chemotherapy were higher in younger women with HR+, HER2- breast cancer, indicating a direct effect of chemotherapy on the disease and that age was an important prognostic factor.

The data on the induction of amenorrhea by chemotherapy is also not as clearcut as it seems, she commented. Chemotherapy does not achieve 100% amenorrhea, and gonadotropin-releasing hormone analogues are unable to suppress ovarian function in 20% of women.

Dr. Loibl concluded that the “chemotherapy effect is there, it is higher in young women with HR+, HER2- breast cancer,” and that the effect has two components.

“There is a direct cytotoxic effect which cannot be neglected, and there is an endocrine effect on the ovarian function suppression,” she argued.

“I think both are needed in young premenopausal patients,” she added.
 

Audience responses

After the debate, the audience was polled on what effect they thought chemotherapy was having in lower-risk HR+, HER2- breast cancer patients. About two-thirds responded that it was all or mostly due to ovarian function suppression.

However, the next question split the audience. They were presented with a clinical scenario: a 43-year-old woman with a mammographically detected 1.4-cm, intermediate grade, HR+, HER2- breast cancer who also had metastatic disease in one of three sentinel lymph nodes and whose recurrence score was 13.

When asked about the treatment plan they would choose for this patient, the audience was split over whether to opt for chemoendocrine therapy or endocrine therapy alone.

A similar clinical question was posited recently on Twitter, when Angela Toss, MD, PhD, from the University of Modena and Reggio Emilia, Italy, asked respondents which they would chose from among three options.

From the 815 votes that were cast, 46% chose Oncotype DX testing to determine the likely benefit of chemotherapy, 48% chose chemotherapy, and 6% picked ovarian function suppression and an aromatase inhibitor.

In response, Paolo Tarantino, MD, from the Dana-Farber Cancer Institute, commented: “If you had any doubt of which is the most controversial topic in breast oncology, doubt no more. 815 votes, no consensus.”

Approached for comment, Eric Winer, MD, director of the Yale Cancer Center, New Haven, Conn., said that the data from RxPONDER “in many ways was helpful, but ... it created about as many questions as it answered, if not more.”

Because the results showed a benefit from chemotherapy for premenopausal women but not for postmenopausal women with breast cancer, Dr. Winer told this news organization that one of the outstanding questions is “whether premenopausal women are fundamentally different from postmenopausal women ... and my answer to that is that is very unlikely.”

Dr. Winer added that the “real tragedy” of this trial was that it did not include women with more than three positive nodes, particularly those who have a low recurrence score, he said.

Clinicians are therefore left either “extrapolating” data from those with fewer nodes or “marching down a path that we’ve taken for years of just giving those people chemotherapy routinely,” even though there may be no benefit, Dr. Winer commented.

Another expert who was approached for comment had a different take on the data. Matteo Lambertini, MD, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, agreed with Loibl’s argument that chemotherapy has a cytotoxic effect in premenopausal women with HR+, HER2- breast cancer in addition to its effect on ovarian function suppression.

He did not agree, however, that there is a question mark over what to do for patients with more than three positive lymph nodes.

Dr. Lambertini said in an interview that he thinks “too much” trust is placed in genomic testing and that there is a “risk of forgetting about all the other factors that we normally use to make our treatment choices.”

A patient with five positive nodes will benefit from chemotherapy, “even if she had a very low recurrence score,” he said, “because there is a very high clinical risk of disease recurrence,” and chemotherapy “is of benefit” in these situations, he asserted.

Dr. Lambertini said that the RxPONDER results – and also studies such as TAILORx, which demonstrated the ability of Oncotype DX to identify which patients with early breast cancer could skip chemotherapy – show that “chemotherapy has a role to play” and that most patients should receive it.

He suggested, however, that “probably the benefit of chemotherapy is smaller” in real life than was seen in these trials, because in the trials, they did not use optimal adjuvant endocrine therapy.
 

Treating individual patients

When it comes to making treatment decisions for individual patients, Dr. Winer said he has a “conversation with people about what the results of the study showed and what [he believes] that they need.”

For patients whose Oncotype DX score is in the “very low range, I do not recommend chemotherapy,” he said, preferring instead to use endocrine therapy for ovarian function suppression.

For women with a more intermediate score, “I explain that I don’t think we have an answer and that, if they would want to take the most traditional and conservative path, it would be to get chemotherapy.

“But I’m certainly not rigid about my recommendations, and I’m particularly open” to ovarian function suppression for a premenopausal woman with an Onctyope DX score of 20 and two positive nodes who does not have “other adverse features.”

“Ultimately, what pushes me in one direction or another,” Dr. Winer said, aside from number of positive nodes or the size of the tumor, “is the patient’s preferences.”

This was a theme taken up by Kim Sabelko, PhD, vice-president of scientific strategy and programs at Susan G. Komen, Dallas.

The results from RxPONDER and similar studies are “really interesting,” as researchers are “working out how to individualize treatment,” and that it is not a matter of “one size fits all.”

“We need to understand when to use chemotherapy and other drugs, and more importantly, when not to, because we don’t want to overtreat people who don’t necessarily need these drugs,” she commented.

Dr. Sabelko emphasized that treatment decisions “should be shared” between the patient and their doctor, and she noted that there “will be some people who are going to refuse chemotherapy for different reasons.”

These clinical trial results help clinicians to explain the risks and benefits of treatment options, but the treatment decision should be taken “together” with the patient, she emphasized.

Dr. Gnant has relationships with Sandoz, Amge, Daiichi Sankyo, AstraZeneca, Eli Lilly, Nanostring, Novartis, Pierre Fabre, TLC Pharmaceuticals, and Life Brain. Dr. Loibl has relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Meyers Squibb, Celgene, Daiichi Sankyo, Eirgenix, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Medscape, Puma, Roche, Samsung, Seagen, VM Scope, and GBG Forschungs.

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

Is this the most controversial topic in breast oncology? Quite likely: the results of a recent online poll show split votes and no consensus.

The topic is the use of chemotherapy for premenopausal women with early-stage hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer.

Is the use of chemo in this patient population merely a “graceless” means of achieving ovarian function suppression, as one expert argued in a recent debate?

Or does it offer a distinct cytotoxic benefit, as the other expert countered?

The debate was held during the recent San Antonio Breast Cancer Symposium (SABCS), at which new results were presented that increased the controversy.

The controversy had arisen the previous year over results from the RxPONDER trial.

Five-year follow-up data from RxPONDER showed that adding chemotherapy to endocrine therapy did not improve outcomes over endocrine therapy alone for postmenopausal women with low-risk, node-positive HR+, HER2- breast cancer. This suggests that older women with early-stage breast cancer may safely forgo chemotherapy.

However, the same trial included premenopausal women with the same disease profile, and the results in this subgroup showed that there was benefit from chemotherapy, with a 5-year invasive disease-free survival (IDFS) rate of 94.2%, versus 89.0% for endocrine therapy alone (P = .0004).

The results were immediately controversial.

Some experts suggested the effect was due to the chemotherapy incidentally causing ovarian suppression, not the cytotoxic effect of the drugs on cancer cells. These experts were skeptical about the suggestion that chemotherapy works differently in premenopausal women than it does in postmenopausal women.

Some clinicians feel the lack of clarity creates an opportunity for greater discussion with women when making the treatment decision.

“When I have this conversation with patients, it’s really nuanced,” Stephanie L. Graff, MD, director of breast oncology, Lifespan Cancer Institute, Providence, R.I., told this news organization.

“I would choose chemotherapy for myself, but I’m a chemotherapy doctor, so I’m very comfortable with these medications and their side effects, and I am also very familiar with the slow burn of the side effects of endocrine therapy,” she said.

But for patients who are hearing their options for the first time, the idea of chemotherapy “feels scary,” and there is “a lot of stigma” associated with it, she commented.

Ultimately, she believes in offering patients as much information as possible, inasmuch as “knowledge is power.”

For Dr. Graff, the message from RxPONDER was that, in premenopausal patients with lymph node positive, HR+ breast cancer, “all comers benefited from chemotherapy.”

“And so if the goal is to be maximally aggressive and optimally lower your risk of distant recurrence, which is a life-threatening event, chemotherapy should offered.”

But chemotherapy comes with side effects, so it’s an important conversation to have with patients; RxPONDER showed that the absolute difference in the rate of distant recurrence with chemotherapy was relatively minor, she added.
 

Debate rages on

The debate at SABCS was moderated by Harold J. Burstein, MD, PhD, from the Dana-Farber Cancer Institute, Boston, who commented that if this was “a compelling question last week in clinic, it has now become red hot.”

At the meeting, held in December 2021, new longer-term data from the SOFT and TEXT clinical trials were presented, showing that ovarian suppression with tamoxifen plus an aromatase inhibitor provides a greater reduction in long-term risk of recurrence than tamoxifen alone.

Moreover, updated results from RxPONDER presented at the same session revealed that chemoendocrine therapy was associated with longer IDFS and distant relapse-free survival than endocrine therapy alone for women with one to three positive lymph nodes and a recurrence score of 25 or lower on the Oncotype DX (Genomic Health) 21-gene breast cancer assay.

Dr. Burstein said the debate over the use of chemotherapy in premenopausal women “is the most interesting question right now in early-stage breast cancer.”

The debate focused on the effect of chemotherapy in these patients – was it all down to ovarian function suppression?

Yes, argued Michael Gnant, MD, from the Medical University of Vienna.

Data from “modern adjuvant chemotherapy trials” suggest that chemo offers a 2%-3% benefit in distant disease-free survival at 5 years for premenopausal women, he noted. But the effect is much larger with ovarian function suppression via endocrine therapy, which provides 5-year disease-free and overall survival benefits of 9%-13%.

Older studies have shown that the benefit with chemotherapy is seen only in women who experience amenorrhea with the cytotoxic drugs, Dr. Gnant noted.

“In short, if you give adjuvant chemotherapy and you induce amenorrhea, then there is going to be a survival difference,” he said. “But if you give adjuvant chemotherapy and there is no amenorrhea, there won’t be an outcome difference.”

The ABSCG-05 trial, which compared endocrine therapy with chemotherapy, showed that “in the presence of optimal endocrine adjuvant treatment, adjuvant chemotherapy doesn’t add anything, because you have already achieved the effect of treatment-induced amenorrhea.”

So Dr. Gnant argued that the effect of chemotherapy in RxPONDER was due to ovarian function suppression.

But the real question is: “What does it mean for clinical practice?”

Dr. Gnant asserted that for the “large group of lower-risk premenopausal patients, tamoxifen will be good enough,” while those at moderate or intermediate risk should receive ovarian function suppression with either tamoxifen or an aromatase inhibitor, with the choice dictated by their adverse effects.

Chemotherapy “is just a graceless method of ovarian function suppression and should only be given to high-risk patients and to patients with endocrine nonresponsive disease,” he argued.

On the other side of the debate, Sibylle Loibl, MD, PhD, from the Centre of Hematology and Oncology, Bethanien, Frankfurt, argued that the effect is not all due to ovarian function suppression and that chemotherapy also has a cytotoxic effect in these patients.

“We need chemotherapy” because “cancer in young women is biologically different,” she asserted.

Dr. Loibl pointed to data currently awaiting publication in the Journal of the National Cancer Institute that suggest that younger women have “higher immune gene expression” that may make them more chemotherapy sensitive, and lower expression of hormone receptor genes, which “could make them less endocrine sensitive.”

She also cited data from a study from her own group that showed that pathologic complete response rates to neoadjuvant chemotherapy were higher in younger women with HR+, HER2- breast cancer, indicating a direct effect of chemotherapy on the disease and that age was an important prognostic factor.

The data on the induction of amenorrhea by chemotherapy is also not as clearcut as it seems, she commented. Chemotherapy does not achieve 100% amenorrhea, and gonadotropin-releasing hormone analogues are unable to suppress ovarian function in 20% of women.

Dr. Loibl concluded that the “chemotherapy effect is there, it is higher in young women with HR+, HER2- breast cancer,” and that the effect has two components.

“There is a direct cytotoxic effect which cannot be neglected, and there is an endocrine effect on the ovarian function suppression,” she argued.

“I think both are needed in young premenopausal patients,” she added.
 

Audience responses

After the debate, the audience was polled on what effect they thought chemotherapy was having in lower-risk HR+, HER2- breast cancer patients. About two-thirds responded that it was all or mostly due to ovarian function suppression.

However, the next question split the audience. They were presented with a clinical scenario: a 43-year-old woman with a mammographically detected 1.4-cm, intermediate grade, HR+, HER2- breast cancer who also had metastatic disease in one of three sentinel lymph nodes and whose recurrence score was 13.

When asked about the treatment plan they would choose for this patient, the audience was split over whether to opt for chemoendocrine therapy or endocrine therapy alone.

A similar clinical question was posited recently on Twitter, when Angela Toss, MD, PhD, from the University of Modena and Reggio Emilia, Italy, asked respondents which they would chose from among three options.

From the 815 votes that were cast, 46% chose Oncotype DX testing to determine the likely benefit of chemotherapy, 48% chose chemotherapy, and 6% picked ovarian function suppression and an aromatase inhibitor.

In response, Paolo Tarantino, MD, from the Dana-Farber Cancer Institute, commented: “If you had any doubt of which is the most controversial topic in breast oncology, doubt no more. 815 votes, no consensus.”

Approached for comment, Eric Winer, MD, director of the Yale Cancer Center, New Haven, Conn., said that the data from RxPONDER “in many ways was helpful, but ... it created about as many questions as it answered, if not more.”

Because the results showed a benefit from chemotherapy for premenopausal women but not for postmenopausal women with breast cancer, Dr. Winer told this news organization that one of the outstanding questions is “whether premenopausal women are fundamentally different from postmenopausal women ... and my answer to that is that is very unlikely.”

Dr. Winer added that the “real tragedy” of this trial was that it did not include women with more than three positive nodes, particularly those who have a low recurrence score, he said.

Clinicians are therefore left either “extrapolating” data from those with fewer nodes or “marching down a path that we’ve taken for years of just giving those people chemotherapy routinely,” even though there may be no benefit, Dr. Winer commented.

Another expert who was approached for comment had a different take on the data. Matteo Lambertini, MD, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, agreed with Loibl’s argument that chemotherapy has a cytotoxic effect in premenopausal women with HR+, HER2- breast cancer in addition to its effect on ovarian function suppression.

He did not agree, however, that there is a question mark over what to do for patients with more than three positive lymph nodes.

Dr. Lambertini said in an interview that he thinks “too much” trust is placed in genomic testing and that there is a “risk of forgetting about all the other factors that we normally use to make our treatment choices.”

A patient with five positive nodes will benefit from chemotherapy, “even if she had a very low recurrence score,” he said, “because there is a very high clinical risk of disease recurrence,” and chemotherapy “is of benefit” in these situations, he asserted.

Dr. Lambertini said that the RxPONDER results – and also studies such as TAILORx, which demonstrated the ability of Oncotype DX to identify which patients with early breast cancer could skip chemotherapy – show that “chemotherapy has a role to play” and that most patients should receive it.

He suggested, however, that “probably the benefit of chemotherapy is smaller” in real life than was seen in these trials, because in the trials, they did not use optimal adjuvant endocrine therapy.
 

Treating individual patients

When it comes to making treatment decisions for individual patients, Dr. Winer said he has a “conversation with people about what the results of the study showed and what [he believes] that they need.”

For patients whose Oncotype DX score is in the “very low range, I do not recommend chemotherapy,” he said, preferring instead to use endocrine therapy for ovarian function suppression.

For women with a more intermediate score, “I explain that I don’t think we have an answer and that, if they would want to take the most traditional and conservative path, it would be to get chemotherapy.

“But I’m certainly not rigid about my recommendations, and I’m particularly open” to ovarian function suppression for a premenopausal woman with an Onctyope DX score of 20 and two positive nodes who does not have “other adverse features.”

“Ultimately, what pushes me in one direction or another,” Dr. Winer said, aside from number of positive nodes or the size of the tumor, “is the patient’s preferences.”

This was a theme taken up by Kim Sabelko, PhD, vice-president of scientific strategy and programs at Susan G. Komen, Dallas.

The results from RxPONDER and similar studies are “really interesting,” as researchers are “working out how to individualize treatment,” and that it is not a matter of “one size fits all.”

“We need to understand when to use chemotherapy and other drugs, and more importantly, when not to, because we don’t want to overtreat people who don’t necessarily need these drugs,” she commented.

Dr. Sabelko emphasized that treatment decisions “should be shared” between the patient and their doctor, and she noted that there “will be some people who are going to refuse chemotherapy for different reasons.”

These clinical trial results help clinicians to explain the risks and benefits of treatment options, but the treatment decision should be taken “together” with the patient, she emphasized.

Dr. Gnant has relationships with Sandoz, Amge, Daiichi Sankyo, AstraZeneca, Eli Lilly, Nanostring, Novartis, Pierre Fabre, TLC Pharmaceuticals, and Life Brain. Dr. Loibl has relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Meyers Squibb, Celgene, Daiichi Sankyo, Eirgenix, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Medscape, Puma, Roche, Samsung, Seagen, VM Scope, and GBG Forschungs.

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

Is this the most controversial topic in breast oncology? Quite likely: the results of a recent online poll show split votes and no consensus.

The topic is the use of chemotherapy for premenopausal women with early-stage hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer.

Is the use of chemo in this patient population merely a “graceless” means of achieving ovarian function suppression, as one expert argued in a recent debate?

Or does it offer a distinct cytotoxic benefit, as the other expert countered?

The debate was held during the recent San Antonio Breast Cancer Symposium (SABCS), at which new results were presented that increased the controversy.

The controversy had arisen the previous year over results from the RxPONDER trial.

Five-year follow-up data from RxPONDER showed that adding chemotherapy to endocrine therapy did not improve outcomes over endocrine therapy alone for postmenopausal women with low-risk, node-positive HR+, HER2- breast cancer. This suggests that older women with early-stage breast cancer may safely forgo chemotherapy.

However, the same trial included premenopausal women with the same disease profile, and the results in this subgroup showed that there was benefit from chemotherapy, with a 5-year invasive disease-free survival (IDFS) rate of 94.2%, versus 89.0% for endocrine therapy alone (P = .0004).

The results were immediately controversial.

Some experts suggested the effect was due to the chemotherapy incidentally causing ovarian suppression, not the cytotoxic effect of the drugs on cancer cells. These experts were skeptical about the suggestion that chemotherapy works differently in premenopausal women than it does in postmenopausal women.

Some clinicians feel the lack of clarity creates an opportunity for greater discussion with women when making the treatment decision.

“When I have this conversation with patients, it’s really nuanced,” Stephanie L. Graff, MD, director of breast oncology, Lifespan Cancer Institute, Providence, R.I., told this news organization.

“I would choose chemotherapy for myself, but I’m a chemotherapy doctor, so I’m very comfortable with these medications and their side effects, and I am also very familiar with the slow burn of the side effects of endocrine therapy,” she said.

But for patients who are hearing their options for the first time, the idea of chemotherapy “feels scary,” and there is “a lot of stigma” associated with it, she commented.

Ultimately, she believes in offering patients as much information as possible, inasmuch as “knowledge is power.”

For Dr. Graff, the message from RxPONDER was that, in premenopausal patients with lymph node positive, HR+ breast cancer, “all comers benefited from chemotherapy.”

“And so if the goal is to be maximally aggressive and optimally lower your risk of distant recurrence, which is a life-threatening event, chemotherapy should offered.”

But chemotherapy comes with side effects, so it’s an important conversation to have with patients; RxPONDER showed that the absolute difference in the rate of distant recurrence with chemotherapy was relatively minor, she added.
 

Debate rages on

The debate at SABCS was moderated by Harold J. Burstein, MD, PhD, from the Dana-Farber Cancer Institute, Boston, who commented that if this was “a compelling question last week in clinic, it has now become red hot.”

At the meeting, held in December 2021, new longer-term data from the SOFT and TEXT clinical trials were presented, showing that ovarian suppression with tamoxifen plus an aromatase inhibitor provides a greater reduction in long-term risk of recurrence than tamoxifen alone.

Moreover, updated results from RxPONDER presented at the same session revealed that chemoendocrine therapy was associated with longer IDFS and distant relapse-free survival than endocrine therapy alone for women with one to three positive lymph nodes and a recurrence score of 25 or lower on the Oncotype DX (Genomic Health) 21-gene breast cancer assay.

Dr. Burstein said the debate over the use of chemotherapy in premenopausal women “is the most interesting question right now in early-stage breast cancer.”

The debate focused on the effect of chemotherapy in these patients – was it all down to ovarian function suppression?

Yes, argued Michael Gnant, MD, from the Medical University of Vienna.

Data from “modern adjuvant chemotherapy trials” suggest that chemo offers a 2%-3% benefit in distant disease-free survival at 5 years for premenopausal women, he noted. But the effect is much larger with ovarian function suppression via endocrine therapy, which provides 5-year disease-free and overall survival benefits of 9%-13%.

Older studies have shown that the benefit with chemotherapy is seen only in women who experience amenorrhea with the cytotoxic drugs, Dr. Gnant noted.

“In short, if you give adjuvant chemotherapy and you induce amenorrhea, then there is going to be a survival difference,” he said. “But if you give adjuvant chemotherapy and there is no amenorrhea, there won’t be an outcome difference.”

The ABSCG-05 trial, which compared endocrine therapy with chemotherapy, showed that “in the presence of optimal endocrine adjuvant treatment, adjuvant chemotherapy doesn’t add anything, because you have already achieved the effect of treatment-induced amenorrhea.”

So Dr. Gnant argued that the effect of chemotherapy in RxPONDER was due to ovarian function suppression.

But the real question is: “What does it mean for clinical practice?”

Dr. Gnant asserted that for the “large group of lower-risk premenopausal patients, tamoxifen will be good enough,” while those at moderate or intermediate risk should receive ovarian function suppression with either tamoxifen or an aromatase inhibitor, with the choice dictated by their adverse effects.

Chemotherapy “is just a graceless method of ovarian function suppression and should only be given to high-risk patients and to patients with endocrine nonresponsive disease,” he argued.

On the other side of the debate, Sibylle Loibl, MD, PhD, from the Centre of Hematology and Oncology, Bethanien, Frankfurt, argued that the effect is not all due to ovarian function suppression and that chemotherapy also has a cytotoxic effect in these patients.

“We need chemotherapy” because “cancer in young women is biologically different,” she asserted.

Dr. Loibl pointed to data currently awaiting publication in the Journal of the National Cancer Institute that suggest that younger women have “higher immune gene expression” that may make them more chemotherapy sensitive, and lower expression of hormone receptor genes, which “could make them less endocrine sensitive.”

She also cited data from a study from her own group that showed that pathologic complete response rates to neoadjuvant chemotherapy were higher in younger women with HR+, HER2- breast cancer, indicating a direct effect of chemotherapy on the disease and that age was an important prognostic factor.

The data on the induction of amenorrhea by chemotherapy is also not as clearcut as it seems, she commented. Chemotherapy does not achieve 100% amenorrhea, and gonadotropin-releasing hormone analogues are unable to suppress ovarian function in 20% of women.

Dr. Loibl concluded that the “chemotherapy effect is there, it is higher in young women with HR+, HER2- breast cancer,” and that the effect has two components.

“There is a direct cytotoxic effect which cannot be neglected, and there is an endocrine effect on the ovarian function suppression,” she argued.

“I think both are needed in young premenopausal patients,” she added.
 

Audience responses

After the debate, the audience was polled on what effect they thought chemotherapy was having in lower-risk HR+, HER2- breast cancer patients. About two-thirds responded that it was all or mostly due to ovarian function suppression.

However, the next question split the audience. They were presented with a clinical scenario: a 43-year-old woman with a mammographically detected 1.4-cm, intermediate grade, HR+, HER2- breast cancer who also had metastatic disease in one of three sentinel lymph nodes and whose recurrence score was 13.

When asked about the treatment plan they would choose for this patient, the audience was split over whether to opt for chemoendocrine therapy or endocrine therapy alone.

A similar clinical question was posited recently on Twitter, when Angela Toss, MD, PhD, from the University of Modena and Reggio Emilia, Italy, asked respondents which they would chose from among three options.

From the 815 votes that were cast, 46% chose Oncotype DX testing to determine the likely benefit of chemotherapy, 48% chose chemotherapy, and 6% picked ovarian function suppression and an aromatase inhibitor.

In response, Paolo Tarantino, MD, from the Dana-Farber Cancer Institute, commented: “If you had any doubt of which is the most controversial topic in breast oncology, doubt no more. 815 votes, no consensus.”

Approached for comment, Eric Winer, MD, director of the Yale Cancer Center, New Haven, Conn., said that the data from RxPONDER “in many ways was helpful, but ... it created about as many questions as it answered, if not more.”

Because the results showed a benefit from chemotherapy for premenopausal women but not for postmenopausal women with breast cancer, Dr. Winer told this news organization that one of the outstanding questions is “whether premenopausal women are fundamentally different from postmenopausal women ... and my answer to that is that is very unlikely.”

Dr. Winer added that the “real tragedy” of this trial was that it did not include women with more than three positive nodes, particularly those who have a low recurrence score, he said.

Clinicians are therefore left either “extrapolating” data from those with fewer nodes or “marching down a path that we’ve taken for years of just giving those people chemotherapy routinely,” even though there may be no benefit, Dr. Winer commented.

Another expert who was approached for comment had a different take on the data. Matteo Lambertini, MD, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, agreed with Loibl’s argument that chemotherapy has a cytotoxic effect in premenopausal women with HR+, HER2- breast cancer in addition to its effect on ovarian function suppression.

He did not agree, however, that there is a question mark over what to do for patients with more than three positive lymph nodes.

Dr. Lambertini said in an interview that he thinks “too much” trust is placed in genomic testing and that there is a “risk of forgetting about all the other factors that we normally use to make our treatment choices.”

A patient with five positive nodes will benefit from chemotherapy, “even if she had a very low recurrence score,” he said, “because there is a very high clinical risk of disease recurrence,” and chemotherapy “is of benefit” in these situations, he asserted.

Dr. Lambertini said that the RxPONDER results – and also studies such as TAILORx, which demonstrated the ability of Oncotype DX to identify which patients with early breast cancer could skip chemotherapy – show that “chemotherapy has a role to play” and that most patients should receive it.

He suggested, however, that “probably the benefit of chemotherapy is smaller” in real life than was seen in these trials, because in the trials, they did not use optimal adjuvant endocrine therapy.
 

Treating individual patients

When it comes to making treatment decisions for individual patients, Dr. Winer said he has a “conversation with people about what the results of the study showed and what [he believes] that they need.”

For patients whose Oncotype DX score is in the “very low range, I do not recommend chemotherapy,” he said, preferring instead to use endocrine therapy for ovarian function suppression.

For women with a more intermediate score, “I explain that I don’t think we have an answer and that, if they would want to take the most traditional and conservative path, it would be to get chemotherapy.

“But I’m certainly not rigid about my recommendations, and I’m particularly open” to ovarian function suppression for a premenopausal woman with an Onctyope DX score of 20 and two positive nodes who does not have “other adverse features.”

“Ultimately, what pushes me in one direction or another,” Dr. Winer said, aside from number of positive nodes or the size of the tumor, “is the patient’s preferences.”

This was a theme taken up by Kim Sabelko, PhD, vice-president of scientific strategy and programs at Susan G. Komen, Dallas.

The results from RxPONDER and similar studies are “really interesting,” as researchers are “working out how to individualize treatment,” and that it is not a matter of “one size fits all.”

“We need to understand when to use chemotherapy and other drugs, and more importantly, when not to, because we don’t want to overtreat people who don’t necessarily need these drugs,” she commented.

Dr. Sabelko emphasized that treatment decisions “should be shared” between the patient and their doctor, and she noted that there “will be some people who are going to refuse chemotherapy for different reasons.”

These clinical trial results help clinicians to explain the risks and benefits of treatment options, but the treatment decision should be taken “together” with the patient, she emphasized.

Dr. Gnant has relationships with Sandoz, Amge, Daiichi Sankyo, AstraZeneca, Eli Lilly, Nanostring, Novartis, Pierre Fabre, TLC Pharmaceuticals, and Life Brain. Dr. Loibl has relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Meyers Squibb, Celgene, Daiichi Sankyo, Eirgenix, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Medscape, Puma, Roche, Samsung, Seagen, VM Scope, and GBG Forschungs.

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

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

 Further support for the benefits of regular exercise in reducing severe COVID-19 outcomes has come from a large study, the first to directly measure physical activity in its participants.

Researchers identified 65,361 members of a South African private health plan who had a COVID-19 diagnosis from March 2020 to June 2021 and matched them with physical activity data during the 2 years prior to the country’s March 2020 lockdown captured by smart devices, and clocked gym attendance and mass event participation in a voluntary healthy lifestyle behavior program linked to the insurer.

UberImages/iStock/Getty Images

In all, 20.4% of participants had engaged in low levels of at least moderate-intensity physical activity per week (0-59 minutes), 34.5% in moderate levels (60-149 minutes), and 45.1% in high levels (150 minutes or more).

Overall, 11.1% were hospitalized as a result of COVID-19, 2.4% were admitted to the ICU, 1.3% required a ventilator, and 1.6% died.

As reported in the British Journal of Sports Medicine, analyses adjusted for demographic and other risk factors showed that, with COVID-19 infection, people with high versus low physical activity had a 34% lower risk for hospitalization (risk ratio, 0.66; 95% confidence interval, 0.63-0.70), a 41% lower risk for ICU admission (RR, 0.59; 95% CI, 0.52-0.66), a 45% lower risk of requiring ventilation (RR, 0.55; 95% CI, 0.47-0.64), and a 42% lower risk for death (RR, 0.58; 95% CI, 0.50-0.68).

Even moderate physical exercise, below the recommended guidelines of at least 150 minutes per week, was associated with several benefits, such as a 13% lower risk for hospitalization (RR, 0.87; 95% CI, 0.82-0.91), a 20% lower risk for ICU admission (RR, 0.80; 95% CI, 0.71-0.89), a 27% lower risk of requiring ventilation (RR, 0.73; 95% CI, 0.62-0.84), and a21% lower risk for death (RR, 0.79; 95% CI, 0.69-0.91).

“Should we come across further waves of this pandemic, our advice from a medical point of view should be to promote and facilitate exercise,” senior author Jon Patricios, MD, Wits Sport and Health, University of the Witwatersrand, Johannesburg, South Africa, said in an interview. “The likelihood is that exercise and vaccination are going to be the two most significant interventions in terms of helping to offload the health care system rather than face the catastrophic events endured a year or so ago.”

The study showed that males are at greater risk than females for severe COVID-19 outcomes, as were patients with essential hypertension, diabetes, and chronic renal disease.

It also suggests that the protective benefit of exercise extends to HIV-positive patients and those with rheumatoid arthritis, two groups previously not evaluated, the authors noted.

The results are comparable with previous reports of self-reported exercise and COVID-19 from the United States and South Korea, although the effect of even moderate exercise was more significant, possibly due to the use of direct measures of exercise rather than self-report, Dr. Patricios suggested.

Previous data suggest that regular physical activity may protect against many viral infections including influenza, rhinovirus, and the reactivation of latent herpes viruses, he noted. However, emerging evidence also points to significant decreases in physical activity during the pandemic.

“Regular physical activity should be a message that is strongly, strongly advocated for, particularly in less well-developed countries where we don’t have access or the resources to afford pharmacological interventions in many of these scenarios,” Dr. Patricios said. “It’s frustrating that the message is not driven strongly enough. It should be part of every government’s agenda.”

The cohort all being members of a medical insurance plan could imply some selection bias based on affordability and limit generalizability of the results, the authors noted. Other limitations include a lack of data on sociodemographic criteria such as education, income, and race, as well as behavioral risk factors such as smoking and diet.

Dr. Patricios and one coauthor are editors of the British Journal of Sports Medicine. Several coauthors are employees of Discovery Health, Johannesburg.

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

 Further support for the benefits of regular exercise in reducing severe COVID-19 outcomes has come from a large study, the first to directly measure physical activity in its participants.

Researchers identified 65,361 members of a South African private health plan who had a COVID-19 diagnosis from March 2020 to June 2021 and matched them with physical activity data during the 2 years prior to the country’s March 2020 lockdown captured by smart devices, and clocked gym attendance and mass event participation in a voluntary healthy lifestyle behavior program linked to the insurer.

UberImages/iStock/Getty Images

In all, 20.4% of participants had engaged in low levels of at least moderate-intensity physical activity per week (0-59 minutes), 34.5% in moderate levels (60-149 minutes), and 45.1% in high levels (150 minutes or more).

Overall, 11.1% were hospitalized as a result of COVID-19, 2.4% were admitted to the ICU, 1.3% required a ventilator, and 1.6% died.

As reported in the British Journal of Sports Medicine, analyses adjusted for demographic and other risk factors showed that, with COVID-19 infection, people with high versus low physical activity had a 34% lower risk for hospitalization (risk ratio, 0.66; 95% confidence interval, 0.63-0.70), a 41% lower risk for ICU admission (RR, 0.59; 95% CI, 0.52-0.66), a 45% lower risk of requiring ventilation (RR, 0.55; 95% CI, 0.47-0.64), and a 42% lower risk for death (RR, 0.58; 95% CI, 0.50-0.68).

Even moderate physical exercise, below the recommended guidelines of at least 150 minutes per week, was associated with several benefits, such as a 13% lower risk for hospitalization (RR, 0.87; 95% CI, 0.82-0.91), a 20% lower risk for ICU admission (RR, 0.80; 95% CI, 0.71-0.89), a 27% lower risk of requiring ventilation (RR, 0.73; 95% CI, 0.62-0.84), and a21% lower risk for death (RR, 0.79; 95% CI, 0.69-0.91).

“Should we come across further waves of this pandemic, our advice from a medical point of view should be to promote and facilitate exercise,” senior author Jon Patricios, MD, Wits Sport and Health, University of the Witwatersrand, Johannesburg, South Africa, said in an interview. “The likelihood is that exercise and vaccination are going to be the two most significant interventions in terms of helping to offload the health care system rather than face the catastrophic events endured a year or so ago.”

The study showed that males are at greater risk than females for severe COVID-19 outcomes, as were patients with essential hypertension, diabetes, and chronic renal disease.

It also suggests that the protective benefit of exercise extends to HIV-positive patients and those with rheumatoid arthritis, two groups previously not evaluated, the authors noted.

The results are comparable with previous reports of self-reported exercise and COVID-19 from the United States and South Korea, although the effect of even moderate exercise was more significant, possibly due to the use of direct measures of exercise rather than self-report, Dr. Patricios suggested.

Previous data suggest that regular physical activity may protect against many viral infections including influenza, rhinovirus, and the reactivation of latent herpes viruses, he noted. However, emerging evidence also points to significant decreases in physical activity during the pandemic.

“Regular physical activity should be a message that is strongly, strongly advocated for, particularly in less well-developed countries where we don’t have access or the resources to afford pharmacological interventions in many of these scenarios,” Dr. Patricios said. “It’s frustrating that the message is not driven strongly enough. It should be part of every government’s agenda.”

The cohort all being members of a medical insurance plan could imply some selection bias based on affordability and limit generalizability of the results, the authors noted. Other limitations include a lack of data on sociodemographic criteria such as education, income, and race, as well as behavioral risk factors such as smoking and diet.

Dr. Patricios and one coauthor are editors of the British Journal of Sports Medicine. Several coauthors are employees of Discovery Health, Johannesburg.

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

 Further support for the benefits of regular exercise in reducing severe COVID-19 outcomes has come from a large study, the first to directly measure physical activity in its participants.

Researchers identified 65,361 members of a South African private health plan who had a COVID-19 diagnosis from March 2020 to June 2021 and matched them with physical activity data during the 2 years prior to the country’s March 2020 lockdown captured by smart devices, and clocked gym attendance and mass event participation in a voluntary healthy lifestyle behavior program linked to the insurer.

UberImages/iStock/Getty Images

In all, 20.4% of participants had engaged in low levels of at least moderate-intensity physical activity per week (0-59 minutes), 34.5% in moderate levels (60-149 minutes), and 45.1% in high levels (150 minutes or more).

Overall, 11.1% were hospitalized as a result of COVID-19, 2.4% were admitted to the ICU, 1.3% required a ventilator, and 1.6% died.

As reported in the British Journal of Sports Medicine, analyses adjusted for demographic and other risk factors showed that, with COVID-19 infection, people with high versus low physical activity had a 34% lower risk for hospitalization (risk ratio, 0.66; 95% confidence interval, 0.63-0.70), a 41% lower risk for ICU admission (RR, 0.59; 95% CI, 0.52-0.66), a 45% lower risk of requiring ventilation (RR, 0.55; 95% CI, 0.47-0.64), and a 42% lower risk for death (RR, 0.58; 95% CI, 0.50-0.68).

Even moderate physical exercise, below the recommended guidelines of at least 150 minutes per week, was associated with several benefits, such as a 13% lower risk for hospitalization (RR, 0.87; 95% CI, 0.82-0.91), a 20% lower risk for ICU admission (RR, 0.80; 95% CI, 0.71-0.89), a 27% lower risk of requiring ventilation (RR, 0.73; 95% CI, 0.62-0.84), and a21% lower risk for death (RR, 0.79; 95% CI, 0.69-0.91).

“Should we come across further waves of this pandemic, our advice from a medical point of view should be to promote and facilitate exercise,” senior author Jon Patricios, MD, Wits Sport and Health, University of the Witwatersrand, Johannesburg, South Africa, said in an interview. “The likelihood is that exercise and vaccination are going to be the two most significant interventions in terms of helping to offload the health care system rather than face the catastrophic events endured a year or so ago.”

The study showed that males are at greater risk than females for severe COVID-19 outcomes, as were patients with essential hypertension, diabetes, and chronic renal disease.

It also suggests that the protective benefit of exercise extends to HIV-positive patients and those with rheumatoid arthritis, two groups previously not evaluated, the authors noted.

The results are comparable with previous reports of self-reported exercise and COVID-19 from the United States and South Korea, although the effect of even moderate exercise was more significant, possibly due to the use of direct measures of exercise rather than self-report, Dr. Patricios suggested.

Previous data suggest that regular physical activity may protect against many viral infections including influenza, rhinovirus, and the reactivation of latent herpes viruses, he noted. However, emerging evidence also points to significant decreases in physical activity during the pandemic.

“Regular physical activity should be a message that is strongly, strongly advocated for, particularly in less well-developed countries where we don’t have access or the resources to afford pharmacological interventions in many of these scenarios,” Dr. Patricios said. “It’s frustrating that the message is not driven strongly enough. It should be part of every government’s agenda.”

The cohort all being members of a medical insurance plan could imply some selection bias based on affordability and limit generalizability of the results, the authors noted. Other limitations include a lack of data on sociodemographic criteria such as education, income, and race, as well as behavioral risk factors such as smoking and diet.

Dr. Patricios and one coauthor are editors of the British Journal of Sports Medicine. Several coauthors are employees of Discovery Health, Johannesburg.

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

Thank Goodness it’s Monday? Sincerely yours, #hustle. 

The COVID-19 pandemic has given us the opportunity to reevaluate what we believe is important and valuable in our life. For some, it’s the opportunity to perform meaningful work; for others, it’s increased financial compensation; and, for the remaining, it may be autonomy (e.g., control over their time). One example of where this mindset has manifested has been in the Great Resignation. 

The Great Resignation refers to the significant increase in resignations that was recorded in April 2021. Resignation rates tend to be higher in fields with high turnover rates (e.g., health care, tech) as a result of increased demand and burnout. Although hustle culture has been an ongoing trend for the last few years, the pandemic has given somewhat of a reality check of the future. 

Hustle culture refers to the embracing of work as a lifestyle such that it takes over other important aspects of your life – in other words, when work-life balance becomes work-work (im)balance. It has also been aptly referred to as burnout culture or grind culture. It’s a bit ironic or counterintuitive to think that stopping work means increased productivity – but it’s true. 

During my undergraduate years, I was always hustling – there wasn’t a moment where I wasn’t studying, doing research, training for my sport, or thinking about how I could do better and be better. It was all about working 24/7 – an illusion to think I was being productive. Now don’t get me wrong, I think the time and effort I invested during those years paid off. However, it also resulted in a sense of dissatisfaction; that is, dissatisfaction that I didn’t explore other potential paths, that I didn’t have the courage to try new things and to be okay with making mistakes. I had extremely narrow tunnel vision because my one and only goal was to go to medical school. 

However, after entering graduate school and actually taking the time to explore other options and career pathways in health, as well as realize that nontraditional pathways are becoming more and more conventional, there is a sense of relief that “failure” is not about changing paths or making mistakes. 

The part of hustle culture that has me hung up is being able to take the time to reflect whether this is what you truly want. I still believe in the value of hard work but I also believe in the value of meaningful and efficient work while also taking the time to reflect. 

The pandemic has shaped a lot of the way we think, what we value, and how we proceed forward. Who we are and what we value is a continuing and ever-growing process, and how we choose to live our lives will play a part. 

I’m curious to hear from you, do you believe in #hustle? Are you part of the #grind culture? Or do you believe we can achieve success, greatness, and satisfaction without the hustle culture?
 

Ms. Lui is an MSc candidate at the University of Toronto, and is with the Mood Disorders Psychopharmacology Unit, Toronto Western Hospital. She has received income from Braxia Scientific. A version of this article first appeared on Medscape.com.

Thank Goodness it’s Monday? Sincerely yours, #hustle. 

The COVID-19 pandemic has given us the opportunity to reevaluate what we believe is important and valuable in our life. For some, it’s the opportunity to perform meaningful work; for others, it’s increased financial compensation; and, for the remaining, it may be autonomy (e.g., control over their time). One example of where this mindset has manifested has been in the Great Resignation. 

The Great Resignation refers to the significant increase in resignations that was recorded in April 2021. Resignation rates tend to be higher in fields with high turnover rates (e.g., health care, tech) as a result of increased demand and burnout. Although hustle culture has been an ongoing trend for the last few years, the pandemic has given somewhat of a reality check of the future. 

Hustle culture refers to the embracing of work as a lifestyle such that it takes over other important aspects of your life – in other words, when work-life balance becomes work-work (im)balance. It has also been aptly referred to as burnout culture or grind culture. It’s a bit ironic or counterintuitive to think that stopping work means increased productivity – but it’s true. 

During my undergraduate years, I was always hustling – there wasn’t a moment where I wasn’t studying, doing research, training for my sport, or thinking about how I could do better and be better. It was all about working 24/7 – an illusion to think I was being productive. Now don’t get me wrong, I think the time and effort I invested during those years paid off. However, it also resulted in a sense of dissatisfaction; that is, dissatisfaction that I didn’t explore other potential paths, that I didn’t have the courage to try new things and to be okay with making mistakes. I had extremely narrow tunnel vision because my one and only goal was to go to medical school. 

However, after entering graduate school and actually taking the time to explore other options and career pathways in health, as well as realize that nontraditional pathways are becoming more and more conventional, there is a sense of relief that “failure” is not about changing paths or making mistakes. 

The part of hustle culture that has me hung up is being able to take the time to reflect whether this is what you truly want. I still believe in the value of hard work but I also believe in the value of meaningful and efficient work while also taking the time to reflect. 

The pandemic has shaped a lot of the way we think, what we value, and how we proceed forward. Who we are and what we value is a continuing and ever-growing process, and how we choose to live our lives will play a part. 

I’m curious to hear from you, do you believe in #hustle? Are you part of the #grind culture? Or do you believe we can achieve success, greatness, and satisfaction without the hustle culture?
 

Ms. Lui is an MSc candidate at the University of Toronto, and is with the Mood Disorders Psychopharmacology Unit, Toronto Western Hospital. She has received income from Braxia Scientific. A version of this article first appeared on Medscape.com.

Thank Goodness it’s Monday? Sincerely yours, #hustle. 

The COVID-19 pandemic has given us the opportunity to reevaluate what we believe is important and valuable in our life. For some, it’s the opportunity to perform meaningful work; for others, it’s increased financial compensation; and, for the remaining, it may be autonomy (e.g., control over their time). One example of where this mindset has manifested has been in the Great Resignation. 

The Great Resignation refers to the significant increase in resignations that was recorded in April 2021. Resignation rates tend to be higher in fields with high turnover rates (e.g., health care, tech) as a result of increased demand and burnout. Although hustle culture has been an ongoing trend for the last few years, the pandemic has given somewhat of a reality check of the future. 

Hustle culture refers to the embracing of work as a lifestyle such that it takes over other important aspects of your life – in other words, when work-life balance becomes work-work (im)balance. It has also been aptly referred to as burnout culture or grind culture. It’s a bit ironic or counterintuitive to think that stopping work means increased productivity – but it’s true. 

During my undergraduate years, I was always hustling – there wasn’t a moment where I wasn’t studying, doing research, training for my sport, or thinking about how I could do better and be better. It was all about working 24/7 – an illusion to think I was being productive. Now don’t get me wrong, I think the time and effort I invested during those years paid off. However, it also resulted in a sense of dissatisfaction; that is, dissatisfaction that I didn’t explore other potential paths, that I didn’t have the courage to try new things and to be okay with making mistakes. I had extremely narrow tunnel vision because my one and only goal was to go to medical school. 

However, after entering graduate school and actually taking the time to explore other options and career pathways in health, as well as realize that nontraditional pathways are becoming more and more conventional, there is a sense of relief that “failure” is not about changing paths or making mistakes. 

The part of hustle culture that has me hung up is being able to take the time to reflect whether this is what you truly want. I still believe in the value of hard work but I also believe in the value of meaningful and efficient work while also taking the time to reflect. 

The pandemic has shaped a lot of the way we think, what we value, and how we proceed forward. Who we are and what we value is a continuing and ever-growing process, and how we choose to live our lives will play a part. 

I’m curious to hear from you, do you believe in #hustle? Are you part of the #grind culture? Or do you believe we can achieve success, greatness, and satisfaction without the hustle culture?
 

Ms. Lui is an MSc candidate at the University of Toronto, and is with the Mood Disorders Psychopharmacology Unit, Toronto Western Hospital. She has received income from Braxia Scientific. A version of this article first appeared on Medscape.com.

BOSTON – Nearly 40% of adults with alopecia areata taking baricitinib, an oral Janus kinase 1 and 2 inhibitor, see significant hair regrowth over 52 weeks, according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.

The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.

Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.

“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”

All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).

The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.

At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.

In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.

Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)

The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.

Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.

"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials. 

The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.

Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.

“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.

While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.

Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection. 

In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release. 

Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.  

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

*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study 

BOSTON – Nearly 40% of adults with alopecia areata taking baricitinib, an oral Janus kinase 1 and 2 inhibitor, see significant hair regrowth over 52 weeks, according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.

The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.

Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.

“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”

All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).

The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.

At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.

In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.

Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)

The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.

Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.

"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials. 

The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.

Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.

“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.

While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.

Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection. 

In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release. 

Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.  

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

*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study 

BOSTON – Nearly 40% of adults with alopecia areata taking baricitinib, an oral Janus kinase 1 and 2 inhibitor, see significant hair regrowth over 52 weeks, according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.

The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.

Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.

“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”

All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).

The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.

At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.

In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.

Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)

The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.

Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.

"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials. 

The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.

Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.

“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.

While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.

Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection. 

In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release. 

Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.  

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

*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study 

Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.

Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.

By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.

The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.

Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.

Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”

The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”

The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.

Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”

The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.

Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.

Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.

By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.

The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.

Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.

Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”

The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”

The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.

Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”

The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.

Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.

Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.

By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.

The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.

Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.

Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”

The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”

The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.

Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”

The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.

During a recent virtual medical malpractice trial, the judge called a break, and the participants left their screens. When the trial resumed a short time later, one juror was missing. The court called his phone, but there was no answer.

“Everyone had to keep waiting and waiting while the bailiff kept trying to call,” recalled Elizabeth Leedom, a medical malpractice defense attorney based in Seattle. “The juror fell asleep.”

The sleeping juror caused a significant delay in the trial, Ms. Leedom said. Finally, he woke up, and the trial was able to continue.

In another instance, a potential juror showed up drunk to a virtual jury selection. The man was slurring his words as he answered questions, Ms. Leedom said, and when asked if he was okay, he admitted that he had a drinking problem. The judge asked whether he had consumed alcohol, and the man admitted that he’d been drinking that day. He was excused from jury selection.

These alarming incidents are among the mishaps that happen during virtual medical malpractice trials. Since the pandemic started, many courts have moved to virtual settings to slow the spread of COVID-19. Although some courts have now shifted back to in-person trials, some areas continue to mandate virtual malpractice trials, hearings, and depositions.

Such trials can save money and are convenient, but legal experts say virtual trials present serious challenges for physicians and raise concerns about fairness. Some jurors are not taking virtual cases seriously or do not stay focused on the subject matter, according to attorneys.

“Virtual trials are not as fair to physicians as in-person trials,” said Andrew DeSimone, a medical malpractice defense attorney based in Lexington, Ky. “It’s too easy not to pay attention in a virtual setting. And when you are dealing with complex medical topics, juror attention is a paramount issue.”
 

Casual settings, constant interruptions during jury selections

Understanding and reaching the jury have been the greatest challenges with virtual and hybrid trials, said Laura Eschleman, a medical liability defense attorney based in Atlanta. Hybrid trials are part virtual and part in person.

Ms. Eschleman has participated in jury selections via Zoom in which jurors lounge in bed during the process and spouses and children waltz into the room as they please, she said.

“With over 36 Zoom boxes of potential jurors, assessing each potential juror was difficult to say the least,” she said. “[Jury selection] has always been an opportunity to introduce the defendant physicians to the jurors as humans; doing it virtually took that away. It is difficult to humanize a box on a screen.”

Regarding one virtual jury selection, Ms. Eschleman said the court had narrowed the pool to a final 12 jurors when one juror’s wife burst into his room and started yelling in front of his computer.

The judge allowed her to speak, and the crying woman begged the judge not to select her husband for the trial because it would disrupt the couple’s child care. After a lengthy exchange, they learned that the child was 16 years old and had his own car. The husband disagreed with his wife and wanted to remain a juror.

“This would have never happened had the twelfth juror been called to an in-person jury selection,” Ms. Eschleman said.

Keeping juries focused while the trial is underway can also be a problem, DeSimone said. He describes the courtroom during malpractice trials as a theater of sorts. Jurors watch intently as witnesses testify, evidence is presented, and the judge gives instructions. During virtual trials, however, watching through a screen doesn’t always yield the same captive audiences, he said.

“During Zoom, it’s much harder to connect with the jury because they won’t be as tuned into it,” he said. “If the jury believes the physician is empathetic, conscientious, caring, and compassionate, they will give the physician the benefit of the doubt, even if something went wrong or a bad outcome occurred. Developing that connection through good eye contact, being a teacher, and showing compassion is the most important thing a physician can do when testifying.”

A related challenge is that medical experts can’t connect as well with jurors, and some may have trouble conveying their message from a screen, said Evan Lyman, a medical malpractice defense attorney based in White Plains, N.Y.

“Some experts like to get out of the witness box and kind of take over the courtroom with a laser pointer or a white board,” he said. “For some, that’s what makes them effective experts. Some experts lose their touch when they can’t do that.”

Technical difficulties during virtual trials can cause further woes, said Kari Adams, vice president of claims for Physicians Insurance – A Mutual Company. She recalled a recent case in which technical problems arose during the defense attorney’s closing arguments.

“It’s hard to see our defense attorneys who are used to using all of their advocacy skills, all of their charisma trying to convey it in a virtual format,” she said. “When it’s disrupted, it can really throw things. A lot of their advocacy and personality can play through, but it’s just a little less in that forum.”
 

Doc fights against virtual trial

When Texas cardiologist Amin Al-Ahmad’s malpractice trial was changed to a virtual format because of COVID-19 concerns, Dr. Al-Ahmad and his attorneys fought the move.

They argued that the malpractice case was too complex for a virtual format and that a video trial would deprive Dr. Al-Ahmad of his rights to due process, including the right to trial by jury.

Dr. Al-Ahmad’s case involved allegations that he had failed to promptly diagnose and treat an atrial esophageal fistula, resulting in a patient’s stroke and ongoing neurologic problems. The trial was expected to last up to 10 days. Nine witnesses were expected to testify, and $1 million in damages were at stake, according to court documents.

“The length of trial anticipated, complexity of the medical issues, the confidential medical information at issue, and the number of anticipated medical records exhibits lead to a real risk of juror ‘Zoom fatigue,’ even if the trial is not interrupted with technology glitches, such as jurors dropping off the link or sound loss,” Dr. Al-Ahmad’s attorneys wrote in a petition to the Texas Supreme Court. “The risks of forcing [the defendants] to trial through the procedure of a remote or virtual jury trial are numerous. Not least of these is the risk that [defendants’] relators will be prevented from presenting an adequate defense or being able to fully preserve error during a virtual trial.”

Another concern regards the lack of uniformity from county to county in conducting a virtual trial, said David A. Wright, an attorney for Dr. Al-Ahmad. Some counties don’t permit them, while others permit parties to opt out of virtual trials, he noted.

“Even those that hold virtual trials seem to have different procedures and rules,” he said. “Travis County, where I have tried my virtual cases, has iPads that they provide to each juror so that they are limited to using just the county iPad for the trial. Others, I have heard, permit jurors to use their own devices. There are simply no uniform rules.”

Despite requests to the trial court and petitions to the appellate and Texas Supreme Court, Dr. Al-Ahmad lost his bid to have his trial delayed until in-person trials resumed. The Texas Supreme Court in late 2021 refused to halt the virtual trial.

Dr. Al-Ahmad, based in Austin, declined to comment through his attorney. Mr. Wright said the court’s denial “was not unexpected.”

Dr. Al-Ahmad’s virtual trial went forward in October 2021, and the jury ruled in his favor.

“We were very pleased with the jury’s verdict,” Mr. Wright said.
 

Are virtual trials ending in higher awards?

In addition to jurors’ not taking their roles as seriously, the casual vibe of virtual trials may also be diminishing how jurors view the verdict’s magnitude.

“Virtual trials don’t have the gravity or the seriousness of a real trial,” Ms. Leedom said. “I don’t think the importance of the jury’s decision weighs on them as much during a Zoom trial as it does an in-person trial.”

Alarmingly, Ms. Leedom said that, in her experience, damages in virtual trials have been higher in comparison with damages awarded during in-person trials.

Ms. Adams agreed with this observation.

“We’ll still win cases, but we’re concerned that, in the cases we lose, the damages can be slightly higher because there hasn’t been that interpersonal connection with the defendant,” she said. “It almost becomes like monopoly money to jurors.”
 

Remember these tips during virtual trials

Physicians undergoing virtual trials may have better experiences if they keep a few tips in mind.

Mr. DeSimone emphasized the importance of eye contact with jurors, which can be tricky during virtual settings. It helps if physicians look at the camera, rather than the screen, while talking.

Physicians should be cognizant of their facial expressions as they watch others speak.

“Don’t roll your eyes like: ‘Oh my gosh, he’s an idiot,’ ” Mr. DeSimone said. “Keep a poker face. Be respectful of what’s going on. Don’t be lulled into letting your guard down.”

Before the virtual trial, practice the cross examination and direct examination with your attorney and record it, Ms. Leedom said. That way, doctors can watch how they present on video and make necessary changes before the real trial. Lighting is also important, she noted. Her firm provides special lamps to clients and witnesses for virtual trials and proceedings.

“The lighting makes a huge difference,” she said.

Its also a good idea for physicians to have a paper copy of the records or exhibits that are going to be used so it’s easy for them to flip through them while on the screen. Physicians should also be mindful of how they come across during video depositions, which are sometimes played during virtual trials, Ms. Adams said.

“If you’re not looking professional during the video deposition – you’re eating, you’re not dressed well – the plaintiff’s attorney will take the most inopportune segment of the deposition and portray the physician as: ‘Look, here’s someone who was careless in the medical care, and look, they don’t even look professional when they’re testifying about this horrifying experience,’ ” she said. “They’ll use the clips to make a very careful provider appear distracted.”
 

Are virtual trials and hearings here to stay?

Whether virtual malpractice trials continue will largely depend on the location in which physicians practice. Some insurance carriers are opting to continue virtual trials, but in some areas, trials are being delayed until in-person proceedings can resume, Ms. Adams said. Some areas never adopted video trials and never ceased in-person trials.

“I think it’s going to be very regionally based,” she said. “Some of the smaller, rural counties just don’t have the capacity or the resources to continue, so they’ll probably just go back to in person.”

Not all virtual proceedings are problematic for physicians, say legal experts. Virtual depositions can be beneficial for doctors because they are less intimidating and confrontational than in-person depositions, Mr. Lyman said.

Additionally, virtual mediations can take much less time than in-person mediations, Ms. Adams said. Video depositions and mediations also save travel costs and reduce time missed from work for physicians.

“But I hope we all go back to in-person trials,” Ms. Leedom said. “Even here in King County, [Washington,] where we’ve done federal and state court trials by Zoom, I’m hopeful that it will go back to in-person trials.”

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

During a recent virtual medical malpractice trial, the judge called a break, and the participants left their screens. When the trial resumed a short time later, one juror was missing. The court called his phone, but there was no answer.

“Everyone had to keep waiting and waiting while the bailiff kept trying to call,” recalled Elizabeth Leedom, a medical malpractice defense attorney based in Seattle. “The juror fell asleep.”

The sleeping juror caused a significant delay in the trial, Ms. Leedom said. Finally, he woke up, and the trial was able to continue.

In another instance, a potential juror showed up drunk to a virtual jury selection. The man was slurring his words as he answered questions, Ms. Leedom said, and when asked if he was okay, he admitted that he had a drinking problem. The judge asked whether he had consumed alcohol, and the man admitted that he’d been drinking that day. He was excused from jury selection.

These alarming incidents are among the mishaps that happen during virtual medical malpractice trials. Since the pandemic started, many courts have moved to virtual settings to slow the spread of COVID-19. Although some courts have now shifted back to in-person trials, some areas continue to mandate virtual malpractice trials, hearings, and depositions.

Such trials can save money and are convenient, but legal experts say virtual trials present serious challenges for physicians and raise concerns about fairness. Some jurors are not taking virtual cases seriously or do not stay focused on the subject matter, according to attorneys.

“Virtual trials are not as fair to physicians as in-person trials,” said Andrew DeSimone, a medical malpractice defense attorney based in Lexington, Ky. “It’s too easy not to pay attention in a virtual setting. And when you are dealing with complex medical topics, juror attention is a paramount issue.”
 

Casual settings, constant interruptions during jury selections

Understanding and reaching the jury have been the greatest challenges with virtual and hybrid trials, said Laura Eschleman, a medical liability defense attorney based in Atlanta. Hybrid trials are part virtual and part in person.

Ms. Eschleman has participated in jury selections via Zoom in which jurors lounge in bed during the process and spouses and children waltz into the room as they please, she said.

“With over 36 Zoom boxes of potential jurors, assessing each potential juror was difficult to say the least,” she said. “[Jury selection] has always been an opportunity to introduce the defendant physicians to the jurors as humans; doing it virtually took that away. It is difficult to humanize a box on a screen.”

Regarding one virtual jury selection, Ms. Eschleman said the court had narrowed the pool to a final 12 jurors when one juror’s wife burst into his room and started yelling in front of his computer.

The judge allowed her to speak, and the crying woman begged the judge not to select her husband for the trial because it would disrupt the couple’s child care. After a lengthy exchange, they learned that the child was 16 years old and had his own car. The husband disagreed with his wife and wanted to remain a juror.

“This would have never happened had the twelfth juror been called to an in-person jury selection,” Ms. Eschleman said.

Keeping juries focused while the trial is underway can also be a problem, DeSimone said. He describes the courtroom during malpractice trials as a theater of sorts. Jurors watch intently as witnesses testify, evidence is presented, and the judge gives instructions. During virtual trials, however, watching through a screen doesn’t always yield the same captive audiences, he said.

“During Zoom, it’s much harder to connect with the jury because they won’t be as tuned into it,” he said. “If the jury believes the physician is empathetic, conscientious, caring, and compassionate, they will give the physician the benefit of the doubt, even if something went wrong or a bad outcome occurred. Developing that connection through good eye contact, being a teacher, and showing compassion is the most important thing a physician can do when testifying.”

A related challenge is that medical experts can’t connect as well with jurors, and some may have trouble conveying their message from a screen, said Evan Lyman, a medical malpractice defense attorney based in White Plains, N.Y.

“Some experts like to get out of the witness box and kind of take over the courtroom with a laser pointer or a white board,” he said. “For some, that’s what makes them effective experts. Some experts lose their touch when they can’t do that.”

Technical difficulties during virtual trials can cause further woes, said Kari Adams, vice president of claims for Physicians Insurance – A Mutual Company. She recalled a recent case in which technical problems arose during the defense attorney’s closing arguments.

“It’s hard to see our defense attorneys who are used to using all of their advocacy skills, all of their charisma trying to convey it in a virtual format,” she said. “When it’s disrupted, it can really throw things. A lot of their advocacy and personality can play through, but it’s just a little less in that forum.”
 

Doc fights against virtual trial

When Texas cardiologist Amin Al-Ahmad’s malpractice trial was changed to a virtual format because of COVID-19 concerns, Dr. Al-Ahmad and his attorneys fought the move.

They argued that the malpractice case was too complex for a virtual format and that a video trial would deprive Dr. Al-Ahmad of his rights to due process, including the right to trial by jury.

Dr. Al-Ahmad’s case involved allegations that he had failed to promptly diagnose and treat an atrial esophageal fistula, resulting in a patient’s stroke and ongoing neurologic problems. The trial was expected to last up to 10 days. Nine witnesses were expected to testify, and $1 million in damages were at stake, according to court documents.

“The length of trial anticipated, complexity of the medical issues, the confidential medical information at issue, and the number of anticipated medical records exhibits lead to a real risk of juror ‘Zoom fatigue,’ even if the trial is not interrupted with technology glitches, such as jurors dropping off the link or sound loss,” Dr. Al-Ahmad’s attorneys wrote in a petition to the Texas Supreme Court. “The risks of forcing [the defendants] to trial through the procedure of a remote or virtual jury trial are numerous. Not least of these is the risk that [defendants’] relators will be prevented from presenting an adequate defense or being able to fully preserve error during a virtual trial.”

Another concern regards the lack of uniformity from county to county in conducting a virtual trial, said David A. Wright, an attorney for Dr. Al-Ahmad. Some counties don’t permit them, while others permit parties to opt out of virtual trials, he noted.

“Even those that hold virtual trials seem to have different procedures and rules,” he said. “Travis County, where I have tried my virtual cases, has iPads that they provide to each juror so that they are limited to using just the county iPad for the trial. Others, I have heard, permit jurors to use their own devices. There are simply no uniform rules.”

Despite requests to the trial court and petitions to the appellate and Texas Supreme Court, Dr. Al-Ahmad lost his bid to have his trial delayed until in-person trials resumed. The Texas Supreme Court in late 2021 refused to halt the virtual trial.

Dr. Al-Ahmad, based in Austin, declined to comment through his attorney. Mr. Wright said the court’s denial “was not unexpected.”

Dr. Al-Ahmad’s virtual trial went forward in October 2021, and the jury ruled in his favor.

“We were very pleased with the jury’s verdict,” Mr. Wright said.
 

Are virtual trials ending in higher awards?

In addition to jurors’ not taking their roles as seriously, the casual vibe of virtual trials may also be diminishing how jurors view the verdict’s magnitude.

“Virtual trials don’t have the gravity or the seriousness of a real trial,” Ms. Leedom said. “I don’t think the importance of the jury’s decision weighs on them as much during a Zoom trial as it does an in-person trial.”

Alarmingly, Ms. Leedom said that, in her experience, damages in virtual trials have been higher in comparison with damages awarded during in-person trials.

Ms. Adams agreed with this observation.

“We’ll still win cases, but we’re concerned that, in the cases we lose, the damages can be slightly higher because there hasn’t been that interpersonal connection with the defendant,” she said. “It almost becomes like monopoly money to jurors.”
 

Remember these tips during virtual trials

Physicians undergoing virtual trials may have better experiences if they keep a few tips in mind.

Mr. DeSimone emphasized the importance of eye contact with jurors, which can be tricky during virtual settings. It helps if physicians look at the camera, rather than the screen, while talking.

Physicians should be cognizant of their facial expressions as they watch others speak.

“Don’t roll your eyes like: ‘Oh my gosh, he’s an idiot,’ ” Mr. DeSimone said. “Keep a poker face. Be respectful of what’s going on. Don’t be lulled into letting your guard down.”

Before the virtual trial, practice the cross examination and direct examination with your attorney and record it, Ms. Leedom said. That way, doctors can watch how they present on video and make necessary changes before the real trial. Lighting is also important, she noted. Her firm provides special lamps to clients and witnesses for virtual trials and proceedings.

“The lighting makes a huge difference,” she said.

Its also a good idea for physicians to have a paper copy of the records or exhibits that are going to be used so it’s easy for them to flip through them while on the screen. Physicians should also be mindful of how they come across during video depositions, which are sometimes played during virtual trials, Ms. Adams said.

“If you’re not looking professional during the video deposition – you’re eating, you’re not dressed well – the plaintiff’s attorney will take the most inopportune segment of the deposition and portray the physician as: ‘Look, here’s someone who was careless in the medical care, and look, they don’t even look professional when they’re testifying about this horrifying experience,’ ” she said. “They’ll use the clips to make a very careful provider appear distracted.”
 

Are virtual trials and hearings here to stay?

Whether virtual malpractice trials continue will largely depend on the location in which physicians practice. Some insurance carriers are opting to continue virtual trials, but in some areas, trials are being delayed until in-person proceedings can resume, Ms. Adams said. Some areas never adopted video trials and never ceased in-person trials.

“I think it’s going to be very regionally based,” she said. “Some of the smaller, rural counties just don’t have the capacity or the resources to continue, so they’ll probably just go back to in person.”

Not all virtual proceedings are problematic for physicians, say legal experts. Virtual depositions can be beneficial for doctors because they are less intimidating and confrontational than in-person depositions, Mr. Lyman said.

Additionally, virtual mediations can take much less time than in-person mediations, Ms. Adams said. Video depositions and mediations also save travel costs and reduce time missed from work for physicians.

“But I hope we all go back to in-person trials,” Ms. Leedom said. “Even here in King County, [Washington,] where we’ve done federal and state court trials by Zoom, I’m hopeful that it will go back to in-person trials.”

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

During a recent virtual medical malpractice trial, the judge called a break, and the participants left their screens. When the trial resumed a short time later, one juror was missing. The court called his phone, but there was no answer.

“Everyone had to keep waiting and waiting while the bailiff kept trying to call,” recalled Elizabeth Leedom, a medical malpractice defense attorney based in Seattle. “The juror fell asleep.”

The sleeping juror caused a significant delay in the trial, Ms. Leedom said. Finally, he woke up, and the trial was able to continue.

In another instance, a potential juror showed up drunk to a virtual jury selection. The man was slurring his words as he answered questions, Ms. Leedom said, and when asked if he was okay, he admitted that he had a drinking problem. The judge asked whether he had consumed alcohol, and the man admitted that he’d been drinking that day. He was excused from jury selection.

These alarming incidents are among the mishaps that happen during virtual medical malpractice trials. Since the pandemic started, many courts have moved to virtual settings to slow the spread of COVID-19. Although some courts have now shifted back to in-person trials, some areas continue to mandate virtual malpractice trials, hearings, and depositions.

Such trials can save money and are convenient, but legal experts say virtual trials present serious challenges for physicians and raise concerns about fairness. Some jurors are not taking virtual cases seriously or do not stay focused on the subject matter, according to attorneys.

“Virtual trials are not as fair to physicians as in-person trials,” said Andrew DeSimone, a medical malpractice defense attorney based in Lexington, Ky. “It’s too easy not to pay attention in a virtual setting. And when you are dealing with complex medical topics, juror attention is a paramount issue.”
 

Casual settings, constant interruptions during jury selections

Understanding and reaching the jury have been the greatest challenges with virtual and hybrid trials, said Laura Eschleman, a medical liability defense attorney based in Atlanta. Hybrid trials are part virtual and part in person.

Ms. Eschleman has participated in jury selections via Zoom in which jurors lounge in bed during the process and spouses and children waltz into the room as they please, she said.

“With over 36 Zoom boxes of potential jurors, assessing each potential juror was difficult to say the least,” she said. “[Jury selection] has always been an opportunity to introduce the defendant physicians to the jurors as humans; doing it virtually took that away. It is difficult to humanize a box on a screen.”

Regarding one virtual jury selection, Ms. Eschleman said the court had narrowed the pool to a final 12 jurors when one juror’s wife burst into his room and started yelling in front of his computer.

The judge allowed her to speak, and the crying woman begged the judge not to select her husband for the trial because it would disrupt the couple’s child care. After a lengthy exchange, they learned that the child was 16 years old and had his own car. The husband disagreed with his wife and wanted to remain a juror.

“This would have never happened had the twelfth juror been called to an in-person jury selection,” Ms. Eschleman said.

Keeping juries focused while the trial is underway can also be a problem, DeSimone said. He describes the courtroom during malpractice trials as a theater of sorts. Jurors watch intently as witnesses testify, evidence is presented, and the judge gives instructions. During virtual trials, however, watching through a screen doesn’t always yield the same captive audiences, he said.

“During Zoom, it’s much harder to connect with the jury because they won’t be as tuned into it,” he said. “If the jury believes the physician is empathetic, conscientious, caring, and compassionate, they will give the physician the benefit of the doubt, even if something went wrong or a bad outcome occurred. Developing that connection through good eye contact, being a teacher, and showing compassion is the most important thing a physician can do when testifying.”

A related challenge is that medical experts can’t connect as well with jurors, and some may have trouble conveying their message from a screen, said Evan Lyman, a medical malpractice defense attorney based in White Plains, N.Y.

“Some experts like to get out of the witness box and kind of take over the courtroom with a laser pointer or a white board,” he said. “For some, that’s what makes them effective experts. Some experts lose their touch when they can’t do that.”

Technical difficulties during virtual trials can cause further woes, said Kari Adams, vice president of claims for Physicians Insurance – A Mutual Company. She recalled a recent case in which technical problems arose during the defense attorney’s closing arguments.

“It’s hard to see our defense attorneys who are used to using all of their advocacy skills, all of their charisma trying to convey it in a virtual format,” she said. “When it’s disrupted, it can really throw things. A lot of their advocacy and personality can play through, but it’s just a little less in that forum.”
 

Doc fights against virtual trial

When Texas cardiologist Amin Al-Ahmad’s malpractice trial was changed to a virtual format because of COVID-19 concerns, Dr. Al-Ahmad and his attorneys fought the move.

They argued that the malpractice case was too complex for a virtual format and that a video trial would deprive Dr. Al-Ahmad of his rights to due process, including the right to trial by jury.

Dr. Al-Ahmad’s case involved allegations that he had failed to promptly diagnose and treat an atrial esophageal fistula, resulting in a patient’s stroke and ongoing neurologic problems. The trial was expected to last up to 10 days. Nine witnesses were expected to testify, and $1 million in damages were at stake, according to court documents.

“The length of trial anticipated, complexity of the medical issues, the confidential medical information at issue, and the number of anticipated medical records exhibits lead to a real risk of juror ‘Zoom fatigue,’ even if the trial is not interrupted with technology glitches, such as jurors dropping off the link or sound loss,” Dr. Al-Ahmad’s attorneys wrote in a petition to the Texas Supreme Court. “The risks of forcing [the defendants] to trial through the procedure of a remote or virtual jury trial are numerous. Not least of these is the risk that [defendants’] relators will be prevented from presenting an adequate defense or being able to fully preserve error during a virtual trial.”

Another concern regards the lack of uniformity from county to county in conducting a virtual trial, said David A. Wright, an attorney for Dr. Al-Ahmad. Some counties don’t permit them, while others permit parties to opt out of virtual trials, he noted.

“Even those that hold virtual trials seem to have different procedures and rules,” he said. “Travis County, where I have tried my virtual cases, has iPads that they provide to each juror so that they are limited to using just the county iPad for the trial. Others, I have heard, permit jurors to use their own devices. There are simply no uniform rules.”

Despite requests to the trial court and petitions to the appellate and Texas Supreme Court, Dr. Al-Ahmad lost his bid to have his trial delayed until in-person trials resumed. The Texas Supreme Court in late 2021 refused to halt the virtual trial.

Dr. Al-Ahmad, based in Austin, declined to comment through his attorney. Mr. Wright said the court’s denial “was not unexpected.”

Dr. Al-Ahmad’s virtual trial went forward in October 2021, and the jury ruled in his favor.

“We were very pleased with the jury’s verdict,” Mr. Wright said.
 

Are virtual trials ending in higher awards?

In addition to jurors’ not taking their roles as seriously, the casual vibe of virtual trials may also be diminishing how jurors view the verdict’s magnitude.

“Virtual trials don’t have the gravity or the seriousness of a real trial,” Ms. Leedom said. “I don’t think the importance of the jury’s decision weighs on them as much during a Zoom trial as it does an in-person trial.”

Alarmingly, Ms. Leedom said that, in her experience, damages in virtual trials have been higher in comparison with damages awarded during in-person trials.

Ms. Adams agreed with this observation.

“We’ll still win cases, but we’re concerned that, in the cases we lose, the damages can be slightly higher because there hasn’t been that interpersonal connection with the defendant,” she said. “It almost becomes like monopoly money to jurors.”
 

Remember these tips during virtual trials

Physicians undergoing virtual trials may have better experiences if they keep a few tips in mind.

Mr. DeSimone emphasized the importance of eye contact with jurors, which can be tricky during virtual settings. It helps if physicians look at the camera, rather than the screen, while talking.

Physicians should be cognizant of their facial expressions as they watch others speak.

“Don’t roll your eyes like: ‘Oh my gosh, he’s an idiot,’ ” Mr. DeSimone said. “Keep a poker face. Be respectful of what’s going on. Don’t be lulled into letting your guard down.”

Before the virtual trial, practice the cross examination and direct examination with your attorney and record it, Ms. Leedom said. That way, doctors can watch how they present on video and make necessary changes before the real trial. Lighting is also important, she noted. Her firm provides special lamps to clients and witnesses for virtual trials and proceedings.

“The lighting makes a huge difference,” she said.

Its also a good idea for physicians to have a paper copy of the records or exhibits that are going to be used so it’s easy for them to flip through them while on the screen. Physicians should also be mindful of how they come across during video depositions, which are sometimes played during virtual trials, Ms. Adams said.

“If you’re not looking professional during the video deposition – you’re eating, you’re not dressed well – the plaintiff’s attorney will take the most inopportune segment of the deposition and portray the physician as: ‘Look, here’s someone who was careless in the medical care, and look, they don’t even look professional when they’re testifying about this horrifying experience,’ ” she said. “They’ll use the clips to make a very careful provider appear distracted.”
 

Are virtual trials and hearings here to stay?

Whether virtual malpractice trials continue will largely depend on the location in which physicians practice. Some insurance carriers are opting to continue virtual trials, but in some areas, trials are being delayed until in-person proceedings can resume, Ms. Adams said. Some areas never adopted video trials and never ceased in-person trials.

“I think it’s going to be very regionally based,” she said. “Some of the smaller, rural counties just don’t have the capacity or the resources to continue, so they’ll probably just go back to in person.”

Not all virtual proceedings are problematic for physicians, say legal experts. Virtual depositions can be beneficial for doctors because they are less intimidating and confrontational than in-person depositions, Mr. Lyman said.

Additionally, virtual mediations can take much less time than in-person mediations, Ms. Adams said. Video depositions and mediations also save travel costs and reduce time missed from work for physicians.

“But I hope we all go back to in-person trials,” Ms. Leedom said. “Even here in King County, [Washington,] where we’ve done federal and state court trials by Zoom, I’m hopeful that it will go back to in-person trials.”

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

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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