Federal Practitioner

It’s been more than a year since we came face to face with an unprecedented, unrelenting pandemic. Determined to overcome, determined to forge ahead, we worked tirelessly.

Drazen Zigic/Getty Images

Hours upon hours, days upon days, months upon months. Hoping for recovery while facing the devastation of death. We were praised, and lauded as heroes as we pleaded for essential protective gear and urged our communities to think critically, act responsibly, and distance safely. From the cities to small towns, we answered the call. Leaving long-practiced specialties, reassigned from our practices and training, we worked together uncertain of the future, but committed to safeguarding our present. Through sacrifice we toiled, leaving our families to protect against contagion, wading through halls of the sick and fighting against the threat of death.

Beginning at the beginning

Addressing these issues starts with training. As a new cohort of eager students enters medical/osteopathic school, the focus should lie not only on foundations of medicine and brute memorization of copious information but also on self-care, wellness checks, and group morale. The same emphasis placed upon patient care and advocacy must also be extended toward ensuring that the next generation of physicians will understand the importance of caring for themselves as much as they care for others.

In the same manner, past stereotypes of ruthless, cut-throat, competition must also evolve. Although the spirit of hard work and perseverance is essential, the manner it propagates is just as important. Aggressive questioning, myriad testing, rigid hierarchies, blind obedience, and ego inflation may separate the pack, but it also reinforces individualism and isolation. Students may shield their internal turmoil behind a mask. The mask of the Super Doctor.

However, as the pandemic has shown, even the most durable of masks will eventually fail. So how do we recognize and accept that help is needed? How do we access support? First, it is vital to acknowledge that there is no shame in asking for help. It is both surprising and reassuring that many of us have been there, an unspoken band of brothers and sisters. Second, remember the acronym for depressive symptoms SIGECAPS (sleep, interest, guilt, energy, concentration, appetite, psychomotor, suicide). Remember that these symptoms may develop gradually or feel sudden and overwhelming. Know that mood lability, tearfulness, and isolation may also be present but confused and disregarded as normal consequences of school, residency, or life as a physician. Third, recognize common behavioral changes associated with anxiety, such as irritability, avoidance, and physical symptoms, including headache, muscle aches, joint pain, GI discomfort, palpitations, and insomnia. Last, reach out to colleagues who have suddenly or gradually withdrawn. Schedule frequent check-ins for one another and do not be afraid to admit that you are human. There is no shame in vulnerability but there is bravery and strength.

If you are in school or residency training, reach out to health centers, training directors, supervisors, family and/or friends. Whether you are an early career physician or amid a decades-long career, connect with your peers, reach out to junior members, offer and accept support. Anonymous hotlines, listservs, email groups, virtual meetings, texts, and phone calls also provide opportunities for wellness checks, pep talks, or venting sessions. All are important. In the case where more specialized help is needed, contact your primary care physician, reach out to colleagues in mental health, contact the Suicide Prevention Lifeline at 1-800 273-8255. Know there is help; you are not alone.

In these unprecedented and uncertain times, remember the African proverb “It takes a village.” To ask for help reveals strength and fortitude. The more we advocate for ourselves and one another, the more we will prevail and shed the myth of infallibility.

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

It’s been more than a year since we came face to face with an unprecedented, unrelenting pandemic. Determined to overcome, determined to forge ahead, we worked tirelessly.

Drazen Zigic/Getty Images

Hours upon hours, days upon days, months upon months. Hoping for recovery while facing the devastation of death. We were praised, and lauded as heroes as we pleaded for essential protective gear and urged our communities to think critically, act responsibly, and distance safely. From the cities to small towns, we answered the call. Leaving long-practiced specialties, reassigned from our practices and training, we worked together uncertain of the future, but committed to safeguarding our present. Through sacrifice we toiled, leaving our families to protect against contagion, wading through halls of the sick and fighting against the threat of death.

Beginning at the beginning

Addressing these issues starts with training. As a new cohort of eager students enters medical/osteopathic school, the focus should lie not only on foundations of medicine and brute memorization of copious information but also on self-care, wellness checks, and group morale. The same emphasis placed upon patient care and advocacy must also be extended toward ensuring that the next generation of physicians will understand the importance of caring for themselves as much as they care for others.

In the same manner, past stereotypes of ruthless, cut-throat, competition must also evolve. Although the spirit of hard work and perseverance is essential, the manner it propagates is just as important. Aggressive questioning, myriad testing, rigid hierarchies, blind obedience, and ego inflation may separate the pack, but it also reinforces individualism and isolation. Students may shield their internal turmoil behind a mask. The mask of the Super Doctor.

However, as the pandemic has shown, even the most durable of masks will eventually fail. So how do we recognize and accept that help is needed? How do we access support? First, it is vital to acknowledge that there is no shame in asking for help. It is both surprising and reassuring that many of us have been there, an unspoken band of brothers and sisters. Second, remember the acronym for depressive symptoms SIGECAPS (sleep, interest, guilt, energy, concentration, appetite, psychomotor, suicide). Remember that these symptoms may develop gradually or feel sudden and overwhelming. Know that mood lability, tearfulness, and isolation may also be present but confused and disregarded as normal consequences of school, residency, or life as a physician. Third, recognize common behavioral changes associated with anxiety, such as irritability, avoidance, and physical symptoms, including headache, muscle aches, joint pain, GI discomfort, palpitations, and insomnia. Last, reach out to colleagues who have suddenly or gradually withdrawn. Schedule frequent check-ins for one another and do not be afraid to admit that you are human. There is no shame in vulnerability but there is bravery and strength.

If you are in school or residency training, reach out to health centers, training directors, supervisors, family and/or friends. Whether you are an early career physician or amid a decades-long career, connect with your peers, reach out to junior members, offer and accept support. Anonymous hotlines, listservs, email groups, virtual meetings, texts, and phone calls also provide opportunities for wellness checks, pep talks, or venting sessions. All are important. In the case where more specialized help is needed, contact your primary care physician, reach out to colleagues in mental health, contact the Suicide Prevention Lifeline at 1-800 273-8255. Know there is help; you are not alone.

In these unprecedented and uncertain times, remember the African proverb “It takes a village.” To ask for help reveals strength and fortitude. The more we advocate for ourselves and one another, the more we will prevail and shed the myth of infallibility.

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

It’s been more than a year since we came face to face with an unprecedented, unrelenting pandemic. Determined to overcome, determined to forge ahead, we worked tirelessly.

Drazen Zigic/Getty Images

Hours upon hours, days upon days, months upon months. Hoping for recovery while facing the devastation of death. We were praised, and lauded as heroes as we pleaded for essential protective gear and urged our communities to think critically, act responsibly, and distance safely. From the cities to small towns, we answered the call. Leaving long-practiced specialties, reassigned from our practices and training, we worked together uncertain of the future, but committed to safeguarding our present. Through sacrifice we toiled, leaving our families to protect against contagion, wading through halls of the sick and fighting against the threat of death.

Beginning at the beginning

Addressing these issues starts with training. As a new cohort of eager students enters medical/osteopathic school, the focus should lie not only on foundations of medicine and brute memorization of copious information but also on self-care, wellness checks, and group morale. The same emphasis placed upon patient care and advocacy must also be extended toward ensuring that the next generation of physicians will understand the importance of caring for themselves as much as they care for others.

In the same manner, past stereotypes of ruthless, cut-throat, competition must also evolve. Although the spirit of hard work and perseverance is essential, the manner it propagates is just as important. Aggressive questioning, myriad testing, rigid hierarchies, blind obedience, and ego inflation may separate the pack, but it also reinforces individualism and isolation. Students may shield their internal turmoil behind a mask. The mask of the Super Doctor.

However, as the pandemic has shown, even the most durable of masks will eventually fail. So how do we recognize and accept that help is needed? How do we access support? First, it is vital to acknowledge that there is no shame in asking for help. It is both surprising and reassuring that many of us have been there, an unspoken band of brothers and sisters. Second, remember the acronym for depressive symptoms SIGECAPS (sleep, interest, guilt, energy, concentration, appetite, psychomotor, suicide). Remember that these symptoms may develop gradually or feel sudden and overwhelming. Know that mood lability, tearfulness, and isolation may also be present but confused and disregarded as normal consequences of school, residency, or life as a physician. Third, recognize common behavioral changes associated with anxiety, such as irritability, avoidance, and physical symptoms, including headache, muscle aches, joint pain, GI discomfort, palpitations, and insomnia. Last, reach out to colleagues who have suddenly or gradually withdrawn. Schedule frequent check-ins for one another and do not be afraid to admit that you are human. There is no shame in vulnerability but there is bravery and strength.

If you are in school or residency training, reach out to health centers, training directors, supervisors, family and/or friends. Whether you are an early career physician or amid a decades-long career, connect with your peers, reach out to junior members, offer and accept support. Anonymous hotlines, listservs, email groups, virtual meetings, texts, and phone calls also provide opportunities for wellness checks, pep talks, or venting sessions. All are important. In the case where more specialized help is needed, contact your primary care physician, reach out to colleagues in mental health, contact the Suicide Prevention Lifeline at 1-800 273-8255. Know there is help; you are not alone.

In these unprecedented and uncertain times, remember the African proverb “It takes a village.” To ask for help reveals strength and fortitude. The more we advocate for ourselves and one another, the more we will prevail and shed the myth of infallibility.

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

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

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

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

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

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

Adhering to a healthy lifestyle may offset the heightened risk of lethal prostate cancer in patients with adverse genetic risk factors, according to results of a large U.S. study.

In men at the highest risk of dying from prostate cancer, having the highest healthy lifestyle scores cut the risk of fatal disease in half, said study author Anna Plym, PhD, of Brigham and Women’s Hospital and Harvard School of Public Health, both in Boston. She presented these findings at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract 822).

Dr. Plym noted that about 58% of the variability in prostate cancer risk is accounted for by genetic factors, with common single-nucleotide polymorphisms (SNPs) accounting for a substantial proportion of prostate cancer susceptibility.

A recent study showed that a polygenic risk score (PRS) derived by combining information from 269 SNPs was “highly predictive” of prostate cancer, Dr. Plym said. There was a 10-fold gradient in disease risk between the lowest and highest genetic risk deciles, and the pattern was consistent across ethnic groups.

In addition, Dr. Plym noted, previous studies have suggested that a healthy lifestyle reduces lethal prostate cancer risk.

What has remained unclear is whether the risk for both developing prostate cancer and experiencing progression to lethal disease can be offset by adherence to a healthy lifestyle.

To investigate, Dr. Plym and colleagues used the 269-SNP PRS to quantify the genetic risk of prostate cancer in 10,443 men enrolled in the Health Professionals Follow-up Study. The men were divided into quartiles according to genetic risk.

The investigators also classified the men using a validated lifestyle score. For this score, one point was given for each of the following: not currently smoking or having quit 10 or more years ago, body mass index under 30 kg/m², high vigorous physical activity, high intake of tomatoes and fatty fish, and low intake of processed meat. Patients with 1-2 points were considered the least healthy, those with 3 points were moderately healthy, and those with 4-6 points were the most healthy.

The outcomes assessed were overall prostate cancer and lethal prostate cancer (i.e., metastatic disease or prostate cancer–specific death).
 

No overall benefit of healthy lifestyle

At a median follow-up of 18 years, 2,111 cases of prostate cancer were observed. And at a median follow-up of 22 years, 238 lethal prostate cancer events occurred.

Men in the highest genetic risk quartile were five times more likely to develop prostate cancer (hazard ratio, 5.39; 95% confidence interval, 4.59-6.34) and three times more likely to develop lethal prostate cancer (HR, 3.43; 95% CI, 2.29-5.14), when compared with men in the lowest genetic risk quartile.

Adherence to a healthy lifestyle did not decrease the risk of prostate cancer overall (HR, 1.01; 95% CI, 0.84-1.22), nor did it affect men in the lower genetic risk quartiles.

However, healthy lifestyle did appear to affect men in the highest genetic risk quartile. Men with the highest healthy lifestyle scores had roughly half the risk of lethal prostate cancer, compared to men with the lowest lifestyle scores (3% vs. 6%).
 

A counterbalance to genetic risk

Dr. Plym observed that the rate of lethal disease in men with the best lifestyle scores matched the rate for the study population as a whole (3%), suggesting that healthy lifestyle may counterbalance high genetic risk.

She added that previous research has confirmed physical activity as a protective factor, but more study is needed to shed light on the relative benefit of the healthy lifestyle components.

In addition, further research is necessary to explain why the benefit was limited to lethal prostate cancer risk in men with the highest genetic risk.

Dr. Plym speculated that the genetic variants contributing to a high PRS may also be the variants that have the strongest interaction with lifestyle factors. For men with a genetic predisposition to prostate cancer, she added, these findings underscore the potential value of surveillance.

“Our findings add to current evidence suggesting that men with a high genetic risk may benefit from a targeted prostate cancer screening program, aiming at detecting a potentially lethal prostate cancer while it is still curable,” she said.

Charles Swanton, MBPhD, of the Francis Crick Institute and UCL Cancer Institute in London, raised the possibility that competing risk issues could be at play.

If a healthy lifestyle leads to longer life, he asked, does that make it more likely that patients will live long enough to die from their prostate cancer because they are not dying from cardiovascular disease, complications of diabetes, etc.? In that case, is the healthy lifestyle really affecting prostate cancer at all?

Dr. Plym responded that, among those in the highest genetic risk group with an unhealthy lifestyle, the increased risk for prostate cancer exceeded the risk for other illnesses.

This study was funded by the DiNovi Family Foundation, the National Cancer Institute, the William Casey Foundation, the Swedish Society for Medical Research, and the Prostate Cancer Foundation. Dr. Plym declared no conflicts of interest. Dr. Swanton disclosed relationships with numerous companies, including Pfizer, Novartis, and GlaxoSmithKline.

Adhering to a healthy lifestyle may offset the heightened risk of lethal prostate cancer in patients with adverse genetic risk factors, according to results of a large U.S. study.

In men at the highest risk of dying from prostate cancer, having the highest healthy lifestyle scores cut the risk of fatal disease in half, said study author Anna Plym, PhD, of Brigham and Women’s Hospital and Harvard School of Public Health, both in Boston. She presented these findings at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract 822).

Dr. Plym noted that about 58% of the variability in prostate cancer risk is accounted for by genetic factors, with common single-nucleotide polymorphisms (SNPs) accounting for a substantial proportion of prostate cancer susceptibility.

A recent study showed that a polygenic risk score (PRS) derived by combining information from 269 SNPs was “highly predictive” of prostate cancer, Dr. Plym said. There was a 10-fold gradient in disease risk between the lowest and highest genetic risk deciles, and the pattern was consistent across ethnic groups.

In addition, Dr. Plym noted, previous studies have suggested that a healthy lifestyle reduces lethal prostate cancer risk.

What has remained unclear is whether the risk for both developing prostate cancer and experiencing progression to lethal disease can be offset by adherence to a healthy lifestyle.

To investigate, Dr. Plym and colleagues used the 269-SNP PRS to quantify the genetic risk of prostate cancer in 10,443 men enrolled in the Health Professionals Follow-up Study. The men were divided into quartiles according to genetic risk.

The investigators also classified the men using a validated lifestyle score. For this score, one point was given for each of the following: not currently smoking or having quit 10 or more years ago, body mass index under 30 kg/m², high vigorous physical activity, high intake of tomatoes and fatty fish, and low intake of processed meat. Patients with 1-2 points were considered the least healthy, those with 3 points were moderately healthy, and those with 4-6 points were the most healthy.

The outcomes assessed were overall prostate cancer and lethal prostate cancer (i.e., metastatic disease or prostate cancer–specific death).
 

No overall benefit of healthy lifestyle

At a median follow-up of 18 years, 2,111 cases of prostate cancer were observed. And at a median follow-up of 22 years, 238 lethal prostate cancer events occurred.

Men in the highest genetic risk quartile were five times more likely to develop prostate cancer (hazard ratio, 5.39; 95% confidence interval, 4.59-6.34) and three times more likely to develop lethal prostate cancer (HR, 3.43; 95% CI, 2.29-5.14), when compared with men in the lowest genetic risk quartile.

Adherence to a healthy lifestyle did not decrease the risk of prostate cancer overall (HR, 1.01; 95% CI, 0.84-1.22), nor did it affect men in the lower genetic risk quartiles.

However, healthy lifestyle did appear to affect men in the highest genetic risk quartile. Men with the highest healthy lifestyle scores had roughly half the risk of lethal prostate cancer, compared to men with the lowest lifestyle scores (3% vs. 6%).
 

A counterbalance to genetic risk

Dr. Plym observed that the rate of lethal disease in men with the best lifestyle scores matched the rate for the study population as a whole (3%), suggesting that healthy lifestyle may counterbalance high genetic risk.

She added that previous research has confirmed physical activity as a protective factor, but more study is needed to shed light on the relative benefit of the healthy lifestyle components.

In addition, further research is necessary to explain why the benefit was limited to lethal prostate cancer risk in men with the highest genetic risk.

Dr. Plym speculated that the genetic variants contributing to a high PRS may also be the variants that have the strongest interaction with lifestyle factors. For men with a genetic predisposition to prostate cancer, she added, these findings underscore the potential value of surveillance.

“Our findings add to current evidence suggesting that men with a high genetic risk may benefit from a targeted prostate cancer screening program, aiming at detecting a potentially lethal prostate cancer while it is still curable,” she said.

Charles Swanton, MBPhD, of the Francis Crick Institute and UCL Cancer Institute in London, raised the possibility that competing risk issues could be at play.

If a healthy lifestyle leads to longer life, he asked, does that make it more likely that patients will live long enough to die from their prostate cancer because they are not dying from cardiovascular disease, complications of diabetes, etc.? In that case, is the healthy lifestyle really affecting prostate cancer at all?

Dr. Plym responded that, among those in the highest genetic risk group with an unhealthy lifestyle, the increased risk for prostate cancer exceeded the risk for other illnesses.

This study was funded by the DiNovi Family Foundation, the National Cancer Institute, the William Casey Foundation, the Swedish Society for Medical Research, and the Prostate Cancer Foundation. Dr. Plym declared no conflicts of interest. Dr. Swanton disclosed relationships with numerous companies, including Pfizer, Novartis, and GlaxoSmithKline.

Adhering to a healthy lifestyle may offset the heightened risk of lethal prostate cancer in patients with adverse genetic risk factors, according to results of a large U.S. study.

In men at the highest risk of dying from prostate cancer, having the highest healthy lifestyle scores cut the risk of fatal disease in half, said study author Anna Plym, PhD, of Brigham and Women’s Hospital and Harvard School of Public Health, both in Boston. She presented these findings at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract 822).

Dr. Plym noted that about 58% of the variability in prostate cancer risk is accounted for by genetic factors, with common single-nucleotide polymorphisms (SNPs) accounting for a substantial proportion of prostate cancer susceptibility.

A recent study showed that a polygenic risk score (PRS) derived by combining information from 269 SNPs was “highly predictive” of prostate cancer, Dr. Plym said. There was a 10-fold gradient in disease risk between the lowest and highest genetic risk deciles, and the pattern was consistent across ethnic groups.

In addition, Dr. Plym noted, previous studies have suggested that a healthy lifestyle reduces lethal prostate cancer risk.

What has remained unclear is whether the risk for both developing prostate cancer and experiencing progression to lethal disease can be offset by adherence to a healthy lifestyle.

To investigate, Dr. Plym and colleagues used the 269-SNP PRS to quantify the genetic risk of prostate cancer in 10,443 men enrolled in the Health Professionals Follow-up Study. The men were divided into quartiles according to genetic risk.

The investigators also classified the men using a validated lifestyle score. For this score, one point was given for each of the following: not currently smoking or having quit 10 or more years ago, body mass index under 30 kg/m², high vigorous physical activity, high intake of tomatoes and fatty fish, and low intake of processed meat. Patients with 1-2 points were considered the least healthy, those with 3 points were moderately healthy, and those with 4-6 points were the most healthy.

The outcomes assessed were overall prostate cancer and lethal prostate cancer (i.e., metastatic disease or prostate cancer–specific death).
 

No overall benefit of healthy lifestyle

At a median follow-up of 18 years, 2,111 cases of prostate cancer were observed. And at a median follow-up of 22 years, 238 lethal prostate cancer events occurred.

Men in the highest genetic risk quartile were five times more likely to develop prostate cancer (hazard ratio, 5.39; 95% confidence interval, 4.59-6.34) and three times more likely to develop lethal prostate cancer (HR, 3.43; 95% CI, 2.29-5.14), when compared with men in the lowest genetic risk quartile.

Adherence to a healthy lifestyle did not decrease the risk of prostate cancer overall (HR, 1.01; 95% CI, 0.84-1.22), nor did it affect men in the lower genetic risk quartiles.

However, healthy lifestyle did appear to affect men in the highest genetic risk quartile. Men with the highest healthy lifestyle scores had roughly half the risk of lethal prostate cancer, compared to men with the lowest lifestyle scores (3% vs. 6%).
 

A counterbalance to genetic risk

Dr. Plym observed that the rate of lethal disease in men with the best lifestyle scores matched the rate for the study population as a whole (3%), suggesting that healthy lifestyle may counterbalance high genetic risk.

She added that previous research has confirmed physical activity as a protective factor, but more study is needed to shed light on the relative benefit of the healthy lifestyle components.

In addition, further research is necessary to explain why the benefit was limited to lethal prostate cancer risk in men with the highest genetic risk.

Dr. Plym speculated that the genetic variants contributing to a high PRS may also be the variants that have the strongest interaction with lifestyle factors. For men with a genetic predisposition to prostate cancer, she added, these findings underscore the potential value of surveillance.

“Our findings add to current evidence suggesting that men with a high genetic risk may benefit from a targeted prostate cancer screening program, aiming at detecting a potentially lethal prostate cancer while it is still curable,” she said.

Charles Swanton, MBPhD, of the Francis Crick Institute and UCL Cancer Institute in London, raised the possibility that competing risk issues could be at play.

If a healthy lifestyle leads to longer life, he asked, does that make it more likely that patients will live long enough to die from their prostate cancer because they are not dying from cardiovascular disease, complications of diabetes, etc.? In that case, is the healthy lifestyle really affecting prostate cancer at all?

Dr. Plym responded that, among those in the highest genetic risk group with an unhealthy lifestyle, the increased risk for prostate cancer exceeded the risk for other illnesses.

This study was funded by the DiNovi Family Foundation, the National Cancer Institute, the William Casey Foundation, the Swedish Society for Medical Research, and the Prostate Cancer Foundation. Dr. Plym declared no conflicts of interest. Dr. Swanton disclosed relationships with numerous companies, including Pfizer, Novartis, and GlaxoSmithKline.

A novel therapy combining platelet-rich plasma (PRP) with follicle-stimulating hormone that is injected directly into the ovaries has the potential to restore ovarian function for women who experience early menopause, possibly allowing for pregnancy without the need for donor eggs.

“The resumption of ovarian function in our participants means women with early menopause could have the opportunity to pursue pregnancy through IVF [in vitro fertilization] using their own eggs,” the authors of the groundbreaking pilot study report.

In the small study, published online March 29 in Menopause, menstruation resumed within a mean of about 5 weeks for 11 of 12 patients with early menopause who were treated with the technique. One patient achieved a clinical pregnancy.

In commenting on the study, Stephanie S. Faubion, MD, medical director of the North American Menopause Society, was cautious in her interpretation, noting the need for more research in larger samples.

“Any pregnancy that results from a regenerative therapy is novel,” she told this news organization. “Still, we are a long way away from this being a standard therapy for women with premature ovarian insufficiency.”
 

Pilot study: Platelet-rich plasma combination with FSH

Early menopause is the cessation of ovarian function at or before the age of 45 years. It is estimated that 12.2% of women experience early menopause. For these women, currently, the only chance of becoming pregnant is with donor eggs.

PRP, an autologous plasma preparation containing more than 10 times the concentration of growth factors and active metabolites than normal plasma, has recently been shown to have the potential to restore the menstrual cycles in perimenopausal women, allowing IVF. It has also been shown to benefit women with premature ovarian insufficiency (POI). However, there have been few reports of pregnancies or live births.

Chao Chin Hsu, MD, PhD, of the National Taiwan University Hospital, Taipei, and colleagues investigated whether the combination of the activated PRP treatment with gondatrophins such as FSH could provide a more robust effect so as to sufficiently stimulate follicles. They used the intraovarian injection of the combination to treat a 38-year-old woman with POI.

The effort was successful, and the woman gave birth to healthy twins.

To further evaluate the approach, the authors conducted a pilot study involving 12 women with early menopause (mean age, 44.4 years) between November 2018 and November 2019.

The women received intraovarian injection with PRP prepared from 40 mL of autologous peripheral blood combined with recombinant FSH.

Following the treatment, 11 of the 12 women experienced resumption of menstruation within a mean of 37 days. For seven patients, menstruation resumed within a month; for three, it resumed within about 2 months; and for one, it resumed after approximately 3 months.

Of note, the menstrual cycles were mostly irregular, with an interval of about 45.6 days.

The women’s average serum FSH level dropped significantly from 70.5 IU/L at baseline to 26.2 IU/L within days of treatment, as did the average luteinizing hormone level (34.8 before and 14.3 IU/L after treatment), indicative of improved ovary function.

For six participants, 10 oocyte retrieval procedures were performed after a mean of about 2 months. Thirteen mature eggs were retrieved, and fertilization via intracytoplasmic sperm injection was attempted, resulting in 10 fertilized oocytes.

Cleavage-stage embryos were transferred into two of the participants. One achieved a clinical pregnancy, defined as a pregnancy that was confirmed by ultrasound and by the presence of a fetal heartbeat. The pregnancy ended in miscarriage at 7 weeks’ gestation.

The length of controlled ovarian stimulation necessary for follicle growth ranged from 8 to 14 days, which the authors note is similar to that seen with women of normal reproductive age.

“Although the use of PRP in reproductive medicine is considered experimental, we demonstrated the restoration of ovarian function in early menopausal women who adopted whole dimension subcortical ovarian injection of PRP/gonadotropin,” the authors write.

“Most remarkably, an early menopausal woman achieved pregnancy after the treatment followed by IVF with her mature ovulating follicle,” they report.
 

Mechanisms, caveats

The mechanisms thought to underlie the success of the approach include increases in ovarian vascularization and stromal cell proliferation and reductions in oxidative stress and cell death in ovaries, the authors explain.

Key caveats with the treatment include the fact that anesthesia and laparoscopy are required, and precise administration is required at 15 injection sites in 1-2 mm of the ovarian subcortical area, which can be difficult to achieve, Dr. Hsu said in an interview.

“If a new instrument could be developed in which physicians can carry out this treatment through a vaginal approach, like the transvaginal retrieval of eggs in IVF treatments,” the approach could become more acceptable, Dr. Hsu added.

The authors call for studies with larger sample sizes and say it will also be interesting to determine effects in different groups: For example, women with cancer who have undergone chemotherapy.

Dr. Faubion, who is director of the Mayo Clinic Women’s Health, Rochester, Minn., says the causes of early menopause could be important in determining the treatment’s efficacy.

“[The therapy’s] success may depend on the reason the woman experienced early menopause: For instance, due to chemotherapy, radiation, virus, autoimmune disease, genetic mutation, or other cause,” she said.

She also noted that cost could be an important factor.

“I don’t see a cost estimate, but it will be substantial,” she said. “So, even if the success rate improves as this technique is further studied, cost and the invasive nature of the treatment may prove to be substantial barriers to this therapy becoming mainstream,” she said.

The authors and Dr. Faubion have disclosed no relevant financial relationships.

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

A novel therapy combining platelet-rich plasma (PRP) with follicle-stimulating hormone that is injected directly into the ovaries has the potential to restore ovarian function for women who experience early menopause, possibly allowing for pregnancy without the need for donor eggs.

“The resumption of ovarian function in our participants means women with early menopause could have the opportunity to pursue pregnancy through IVF [in vitro fertilization] using their own eggs,” the authors of the groundbreaking pilot study report.

In the small study, published online March 29 in Menopause, menstruation resumed within a mean of about 5 weeks for 11 of 12 patients with early menopause who were treated with the technique. One patient achieved a clinical pregnancy.

In commenting on the study, Stephanie S. Faubion, MD, medical director of the North American Menopause Society, was cautious in her interpretation, noting the need for more research in larger samples.

“Any pregnancy that results from a regenerative therapy is novel,” she told this news organization. “Still, we are a long way away from this being a standard therapy for women with premature ovarian insufficiency.”
 

Pilot study: Platelet-rich plasma combination with FSH

Early menopause is the cessation of ovarian function at or before the age of 45 years. It is estimated that 12.2% of women experience early menopause. For these women, currently, the only chance of becoming pregnant is with donor eggs.

PRP, an autologous plasma preparation containing more than 10 times the concentration of growth factors and active metabolites than normal plasma, has recently been shown to have the potential to restore the menstrual cycles in perimenopausal women, allowing IVF. It has also been shown to benefit women with premature ovarian insufficiency (POI). However, there have been few reports of pregnancies or live births.

Chao Chin Hsu, MD, PhD, of the National Taiwan University Hospital, Taipei, and colleagues investigated whether the combination of the activated PRP treatment with gondatrophins such as FSH could provide a more robust effect so as to sufficiently stimulate follicles. They used the intraovarian injection of the combination to treat a 38-year-old woman with POI.

The effort was successful, and the woman gave birth to healthy twins.

To further evaluate the approach, the authors conducted a pilot study involving 12 women with early menopause (mean age, 44.4 years) between November 2018 and November 2019.

The women received intraovarian injection with PRP prepared from 40 mL of autologous peripheral blood combined with recombinant FSH.

Following the treatment, 11 of the 12 women experienced resumption of menstruation within a mean of 37 days. For seven patients, menstruation resumed within a month; for three, it resumed within about 2 months; and for one, it resumed after approximately 3 months.

Of note, the menstrual cycles were mostly irregular, with an interval of about 45.6 days.

The women’s average serum FSH level dropped significantly from 70.5 IU/L at baseline to 26.2 IU/L within days of treatment, as did the average luteinizing hormone level (34.8 before and 14.3 IU/L after treatment), indicative of improved ovary function.

For six participants, 10 oocyte retrieval procedures were performed after a mean of about 2 months. Thirteen mature eggs were retrieved, and fertilization via intracytoplasmic sperm injection was attempted, resulting in 10 fertilized oocytes.

Cleavage-stage embryos were transferred into two of the participants. One achieved a clinical pregnancy, defined as a pregnancy that was confirmed by ultrasound and by the presence of a fetal heartbeat. The pregnancy ended in miscarriage at 7 weeks’ gestation.

The length of controlled ovarian stimulation necessary for follicle growth ranged from 8 to 14 days, which the authors note is similar to that seen with women of normal reproductive age.

“Although the use of PRP in reproductive medicine is considered experimental, we demonstrated the restoration of ovarian function in early menopausal women who adopted whole dimension subcortical ovarian injection of PRP/gonadotropin,” the authors write.

“Most remarkably, an early menopausal woman achieved pregnancy after the treatment followed by IVF with her mature ovulating follicle,” they report.
 

Mechanisms, caveats

The mechanisms thought to underlie the success of the approach include increases in ovarian vascularization and stromal cell proliferation and reductions in oxidative stress and cell death in ovaries, the authors explain.

Key caveats with the treatment include the fact that anesthesia and laparoscopy are required, and precise administration is required at 15 injection sites in 1-2 mm of the ovarian subcortical area, which can be difficult to achieve, Dr. Hsu said in an interview.

“If a new instrument could be developed in which physicians can carry out this treatment through a vaginal approach, like the transvaginal retrieval of eggs in IVF treatments,” the approach could become more acceptable, Dr. Hsu added.

The authors call for studies with larger sample sizes and say it will also be interesting to determine effects in different groups: For example, women with cancer who have undergone chemotherapy.

Dr. Faubion, who is director of the Mayo Clinic Women’s Health, Rochester, Minn., says the causes of early menopause could be important in determining the treatment’s efficacy.

“[The therapy’s] success may depend on the reason the woman experienced early menopause: For instance, due to chemotherapy, radiation, virus, autoimmune disease, genetic mutation, or other cause,” she said.

She also noted that cost could be an important factor.

“I don’t see a cost estimate, but it will be substantial,” she said. “So, even if the success rate improves as this technique is further studied, cost and the invasive nature of the treatment may prove to be substantial barriers to this therapy becoming mainstream,” she said.

The authors and Dr. Faubion have disclosed no relevant financial relationships.

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

A novel therapy combining platelet-rich plasma (PRP) with follicle-stimulating hormone that is injected directly into the ovaries has the potential to restore ovarian function for women who experience early menopause, possibly allowing for pregnancy without the need for donor eggs.

“The resumption of ovarian function in our participants means women with early menopause could have the opportunity to pursue pregnancy through IVF [in vitro fertilization] using their own eggs,” the authors of the groundbreaking pilot study report.

In the small study, published online March 29 in Menopause, menstruation resumed within a mean of about 5 weeks for 11 of 12 patients with early menopause who were treated with the technique. One patient achieved a clinical pregnancy.

In commenting on the study, Stephanie S. Faubion, MD, medical director of the North American Menopause Society, was cautious in her interpretation, noting the need for more research in larger samples.

“Any pregnancy that results from a regenerative therapy is novel,” she told this news organization. “Still, we are a long way away from this being a standard therapy for women with premature ovarian insufficiency.”
 

Pilot study: Platelet-rich plasma combination with FSH

Early menopause is the cessation of ovarian function at or before the age of 45 years. It is estimated that 12.2% of women experience early menopause. For these women, currently, the only chance of becoming pregnant is with donor eggs.

PRP, an autologous plasma preparation containing more than 10 times the concentration of growth factors and active metabolites than normal plasma, has recently been shown to have the potential to restore the menstrual cycles in perimenopausal women, allowing IVF. It has also been shown to benefit women with premature ovarian insufficiency (POI). However, there have been few reports of pregnancies or live births.

Chao Chin Hsu, MD, PhD, of the National Taiwan University Hospital, Taipei, and colleagues investigated whether the combination of the activated PRP treatment with gondatrophins such as FSH could provide a more robust effect so as to sufficiently stimulate follicles. They used the intraovarian injection of the combination to treat a 38-year-old woman with POI.

The effort was successful, and the woman gave birth to healthy twins.

To further evaluate the approach, the authors conducted a pilot study involving 12 women with early menopause (mean age, 44.4 years) between November 2018 and November 2019.

The women received intraovarian injection with PRP prepared from 40 mL of autologous peripheral blood combined with recombinant FSH.

Following the treatment, 11 of the 12 women experienced resumption of menstruation within a mean of 37 days. For seven patients, menstruation resumed within a month; for three, it resumed within about 2 months; and for one, it resumed after approximately 3 months.

Of note, the menstrual cycles were mostly irregular, with an interval of about 45.6 days.

The women’s average serum FSH level dropped significantly from 70.5 IU/L at baseline to 26.2 IU/L within days of treatment, as did the average luteinizing hormone level (34.8 before and 14.3 IU/L after treatment), indicative of improved ovary function.

For six participants, 10 oocyte retrieval procedures were performed after a mean of about 2 months. Thirteen mature eggs were retrieved, and fertilization via intracytoplasmic sperm injection was attempted, resulting in 10 fertilized oocytes.

Cleavage-stage embryos were transferred into two of the participants. One achieved a clinical pregnancy, defined as a pregnancy that was confirmed by ultrasound and by the presence of a fetal heartbeat. The pregnancy ended in miscarriage at 7 weeks’ gestation.

The length of controlled ovarian stimulation necessary for follicle growth ranged from 8 to 14 days, which the authors note is similar to that seen with women of normal reproductive age.

“Although the use of PRP in reproductive medicine is considered experimental, we demonstrated the restoration of ovarian function in early menopausal women who adopted whole dimension subcortical ovarian injection of PRP/gonadotropin,” the authors write.

“Most remarkably, an early menopausal woman achieved pregnancy after the treatment followed by IVF with her mature ovulating follicle,” they report.
 

Mechanisms, caveats

The mechanisms thought to underlie the success of the approach include increases in ovarian vascularization and stromal cell proliferation and reductions in oxidative stress and cell death in ovaries, the authors explain.

Key caveats with the treatment include the fact that anesthesia and laparoscopy are required, and precise administration is required at 15 injection sites in 1-2 mm of the ovarian subcortical area, which can be difficult to achieve, Dr. Hsu said in an interview.

“If a new instrument could be developed in which physicians can carry out this treatment through a vaginal approach, like the transvaginal retrieval of eggs in IVF treatments,” the approach could become more acceptable, Dr. Hsu added.

The authors call for studies with larger sample sizes and say it will also be interesting to determine effects in different groups: For example, women with cancer who have undergone chemotherapy.

Dr. Faubion, who is director of the Mayo Clinic Women’s Health, Rochester, Minn., says the causes of early menopause could be important in determining the treatment’s efficacy.

“[The therapy’s] success may depend on the reason the woman experienced early menopause: For instance, due to chemotherapy, radiation, virus, autoimmune disease, genetic mutation, or other cause,” she said.

She also noted that cost could be an important factor.

“I don’t see a cost estimate, but it will be substantial,” she said. “So, even if the success rate improves as this technique is further studied, cost and the invasive nature of the treatment may prove to be substantial barriers to this therapy becoming mainstream,” she said.

The authors and Dr. Faubion have disclosed no relevant financial relationships.

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

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

This article was updated 4/13/21.

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

This article was updated 4/13/21.

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

This article was updated 4/13/21.

After more than 10 hours of intense debate, a Food and Drug Administration advisory panel gave its support to a premarket approval application (PMA) for the TransMedics Organ Care System (OCS) Heart system.

Courtesy Transmedics

The OCS Heart is a portable extracorporeal perfusion and monitoring system designed to keep a donor heart in a normothermic, beating state. The “heart in a box” technology allows donor hearts to be transported across longer distances than is possible with standard cold storage, which can safely preserve donor hearts for about 4 hours.

The Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 12 to 5, with 1 abstention, that the benefits of the OCS Heart System outweigh its risks.

The panel voted in favor of the OCS Heart being effective (10 yes, 6 no, and 2 abstaining) and safe (9 yes, 7 no, 2 abstaining) but not without mixed feelings.

James Blankenship, MD, a cardiologist at the University of New Mexico, Albuquerque, voted yes to all three questions but said: “If it had been compared to standard of care, I would have voted no to all three. But if it’s compared to getting an [left ventricular assist device] LVAD or not getting a heart at all, I would say the benefits outweigh the risks.”

Marc R. Katz, MD, chief of cardiothoracic surgery, Medical University of South Carolina, Charleston, also gave universal support, noting that the rate of heart transplantations has been flat for years. “This is a big step forward toward being able to expand that number. Now all that said, it obviously was a less-than-perfect study and I do think there needs to be some constraints put on the utilization.”

The panel reviewed data from the single-arm OCS Heart EXPAND trial and associated EXPAND Continued Access Protocol (CAP), as well the sponsor’s first OCS Heart trial, PROCEED II.

EXPAND met its effectiveness endpoint, with 88% of donor hearts successfully transplanted, an 8% incidence of severe primary graft dysfunction (PGD) 24 hours after transplantation, and 94.6% survival at 30 days.

Data from 41 patients with 30-day follow-up in the ongoing EXPAND CAP show 91% of donor hearts were utilized, a 2.4% incidence of severe PGD, and 100% 30-day survival.

The sponsor and the FDA clashed over changes made to the trial after the PMA was submitted, the appropriateness of the effectiveness outcome, and claims by the FDA that there was substantial overlap in demographic characteristics between the extended criteria donor hearts in the EXPAND trials and the standard criteria donor hearts in PROCEED II.

TransMedics previously submitted a PMA based on PROCEED II but it noted in submitted documents that it was withdrawn because of “fundamental disagreements with FDA” on the interpretation of a post hoc analysis with United Network for Organ Sharing registry data that identified increased all-cause mortality risk but comparable cardiac-related mortality in patients with OCS hearts.

During the marathon hearing, FDA officials presented several post hoc analyses, including one stratified by donor inclusion criteria, in which 30-day survival estimates were worse in recipients of single-criterion organs than for those receiving donor organs with multiple inclusion criteria (85% vs. 91.4%). In a second analysis, 2-year point estimates of survival also trended lower with donor organs having only one extended criterion.

Reported EXPAND CAP 6- and 12-month survival estimates were 100% and 93%, respectively, which was higher than EXPAND (93% and 84%), but there was substantial censoring (>50%) at 6 months and beyond, FDA officials said.

When EXPAND and CAP data were pooled, modeled survival curves shifted upward but there was a substantial site effect, with a single site contributing 46% of data, which may affect generalizability of the results, they noted.

“I voted yes for safety, no for efficacy, and no for approval and I’d just like to say I found this to be the most difficult vote in my experience on this panel,” John Hirshfeld, MD, University of Pennsylvania, Philadelphia, said. “I was very concerned that the PROCEED data suggests a possible harm, and in the absence of an interpretable comparator for the EXPAND trial, it’s really not possible to decide if there’s efficacy.”

Keith B. Allen, MD, director of surgical research at Saint Luke’s Hospital of Kansas City (Mo.), said, “I voted no on safety; I’m not going to give the company a pass. I think their animal data was sorely lacking and a lot of issues over the last 10 years could have been addressed with some key animal studies.

“For efficacy and risk/benefit, I voted yes for both,” he said. “Had this been standard of care and only PROCEED II, I would have voted no, but I do think there are a lot of hearts that go in the bucket and this is a challenging population.”

More than a dozen physicians and patients spoke at the open public hearing about the potential for the device to expand donor heart utilization, including a recipient whose own father died while waiting on the transplant list. Only about 3 out of every 10 donated hearts are used for transplant. To ensure fair access, particularly for patients in rural areas, federal changes in 2020 mandate that organs be allocated to the sickest patients first.

Data showed that the OCS Heart System was associated with shorter waiting list times, compared with U.S. averages but longer preservation times than cold static preservation.

In all, 13% of accepted donor organs were subsequently turned down after OCS heart preservation. Lactate levels were cited as the principal reason for turn-down but, FDA officials said, the validity of using lactate as a marker for transplantability is unclear.

Pathologic analysis of OCS Heart turned-down donor hearts with stable antemortem hemodynamics, normal or near-normal anatomy and normal ventricular function by echocardiography, and autopsy findings of acute diffuse or multifocal myocardial damage “suggest that in an important proportion of cases the OCS Heart system did not provide effective organ preservation or its use caused severe myocardial damage to what might have been an acceptable graft for transplant,” said Andrew Farb, MD, chief medical officer of the FDA’s Office of Cardiovascular Devices.
 

Proposed indication

In the present PMA, the OCS Heart System is indicated for donor hearts with one or more of the following characteristics: an expected cross-clamp or ischemic time of at least 4 hours because of donor or recipient characteristics; or an expected total cross-clamp time of at least 2 hours plus one of the following risk factors: donor age 55 or older, history of cardiac arrest and downtime of at least 20 minutes, history of alcoholism, history of diabetes, donor ejection fraction of 40%-50%,history of left ventricular hypertrophy, and donor angiogram with luminal irregularities but no significant coronary artery disease

Several members voiced concern about “indication creep” should the device be approved by the FDA, and highlighted the 2-hour cross-clamp time plus wide-ranging risk factors.

“I’m a surgeon and I voted no on all three counts,” said Murray H. Kwon, MD, Ronald Reagan University of California, Los Angeles Medical Center. “As far as risk/benefit, if it was just limited to one group – the 4-hour plus – I would say yes, but if you’re going to tell me that there’s a risk/benefit for the 2-hour with the alcoholic, I don’t know how that was proved in anything.”

Dr. Kwon was also troubled by lack of proper controls and by the one quarter of patients who ended up on mechanical circulatory support in the first 30 days after transplant. “I find that highly aberrant.”

Joaquin E. Cigarroa, MD, head of cardiovascular medicine, Oregon Health & Science University, Portland, said the unmet need for patients with refractory, end-stage heart failure is challenging and quite emotional, but also voted no across the board, citing concerns about a lack of comparator in the EXPAND trials and overall out-of-body ischemic time.

“As it relates to risk/benefit, I thought long and hard about voting yes despite all the unknowns because of this emotion, but ultimately I voted no because of the secondary 2-hours plus alcoholism, diabetes, or minor coronary disease, in which the ischemic burden and ongoing lactate production concern me,” he said.

Although the panel decision is nonbinding, there was strong support from the committee members for a randomized, postapproval trial and more complete animal studies.

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

After more than 10 hours of intense debate, a Food and Drug Administration advisory panel gave its support to a premarket approval application (PMA) for the TransMedics Organ Care System (OCS) Heart system.

Courtesy Transmedics

The OCS Heart is a portable extracorporeal perfusion and monitoring system designed to keep a donor heart in a normothermic, beating state. The “heart in a box” technology allows donor hearts to be transported across longer distances than is possible with standard cold storage, which can safely preserve donor hearts for about 4 hours.

The Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 12 to 5, with 1 abstention, that the benefits of the OCS Heart System outweigh its risks.

The panel voted in favor of the OCS Heart being effective (10 yes, 6 no, and 2 abstaining) and safe (9 yes, 7 no, 2 abstaining) but not without mixed feelings.

James Blankenship, MD, a cardiologist at the University of New Mexico, Albuquerque, voted yes to all three questions but said: “If it had been compared to standard of care, I would have voted no to all three. But if it’s compared to getting an [left ventricular assist device] LVAD or not getting a heart at all, I would say the benefits outweigh the risks.”

Marc R. Katz, MD, chief of cardiothoracic surgery, Medical University of South Carolina, Charleston, also gave universal support, noting that the rate of heart transplantations has been flat for years. “This is a big step forward toward being able to expand that number. Now all that said, it obviously was a less-than-perfect study and I do think there needs to be some constraints put on the utilization.”

The panel reviewed data from the single-arm OCS Heart EXPAND trial and associated EXPAND Continued Access Protocol (CAP), as well the sponsor’s first OCS Heart trial, PROCEED II.

EXPAND met its effectiveness endpoint, with 88% of donor hearts successfully transplanted, an 8% incidence of severe primary graft dysfunction (PGD) 24 hours after transplantation, and 94.6% survival at 30 days.

Data from 41 patients with 30-day follow-up in the ongoing EXPAND CAP show 91% of donor hearts were utilized, a 2.4% incidence of severe PGD, and 100% 30-day survival.

The sponsor and the FDA clashed over changes made to the trial after the PMA was submitted, the appropriateness of the effectiveness outcome, and claims by the FDA that there was substantial overlap in demographic characteristics between the extended criteria donor hearts in the EXPAND trials and the standard criteria donor hearts in PROCEED II.

TransMedics previously submitted a PMA based on PROCEED II but it noted in submitted documents that it was withdrawn because of “fundamental disagreements with FDA” on the interpretation of a post hoc analysis with United Network for Organ Sharing registry data that identified increased all-cause mortality risk but comparable cardiac-related mortality in patients with OCS hearts.

During the marathon hearing, FDA officials presented several post hoc analyses, including one stratified by donor inclusion criteria, in which 30-day survival estimates were worse in recipients of single-criterion organs than for those receiving donor organs with multiple inclusion criteria (85% vs. 91.4%). In a second analysis, 2-year point estimates of survival also trended lower with donor organs having only one extended criterion.

Reported EXPAND CAP 6- and 12-month survival estimates were 100% and 93%, respectively, which was higher than EXPAND (93% and 84%), but there was substantial censoring (>50%) at 6 months and beyond, FDA officials said.

When EXPAND and CAP data were pooled, modeled survival curves shifted upward but there was a substantial site effect, with a single site contributing 46% of data, which may affect generalizability of the results, they noted.

“I voted yes for safety, no for efficacy, and no for approval and I’d just like to say I found this to be the most difficult vote in my experience on this panel,” John Hirshfeld, MD, University of Pennsylvania, Philadelphia, said. “I was very concerned that the PROCEED data suggests a possible harm, and in the absence of an interpretable comparator for the EXPAND trial, it’s really not possible to decide if there’s efficacy.”

Keith B. Allen, MD, director of surgical research at Saint Luke’s Hospital of Kansas City (Mo.), said, “I voted no on safety; I’m not going to give the company a pass. I think their animal data was sorely lacking and a lot of issues over the last 10 years could have been addressed with some key animal studies.

“For efficacy and risk/benefit, I voted yes for both,” he said. “Had this been standard of care and only PROCEED II, I would have voted no, but I do think there are a lot of hearts that go in the bucket and this is a challenging population.”

More than a dozen physicians and patients spoke at the open public hearing about the potential for the device to expand donor heart utilization, including a recipient whose own father died while waiting on the transplant list. Only about 3 out of every 10 donated hearts are used for transplant. To ensure fair access, particularly for patients in rural areas, federal changes in 2020 mandate that organs be allocated to the sickest patients first.

Data showed that the OCS Heart System was associated with shorter waiting list times, compared with U.S. averages but longer preservation times than cold static preservation.

In all, 13% of accepted donor organs were subsequently turned down after OCS heart preservation. Lactate levels were cited as the principal reason for turn-down but, FDA officials said, the validity of using lactate as a marker for transplantability is unclear.

Pathologic analysis of OCS Heart turned-down donor hearts with stable antemortem hemodynamics, normal or near-normal anatomy and normal ventricular function by echocardiography, and autopsy findings of acute diffuse or multifocal myocardial damage “suggest that in an important proportion of cases the OCS Heart system did not provide effective organ preservation or its use caused severe myocardial damage to what might have been an acceptable graft for transplant,” said Andrew Farb, MD, chief medical officer of the FDA’s Office of Cardiovascular Devices.
 

Proposed indication

In the present PMA, the OCS Heart System is indicated for donor hearts with one or more of the following characteristics: an expected cross-clamp or ischemic time of at least 4 hours because of donor or recipient characteristics; or an expected total cross-clamp time of at least 2 hours plus one of the following risk factors: donor age 55 or older, history of cardiac arrest and downtime of at least 20 minutes, history of alcoholism, history of diabetes, donor ejection fraction of 40%-50%,history of left ventricular hypertrophy, and donor angiogram with luminal irregularities but no significant coronary artery disease

Several members voiced concern about “indication creep” should the device be approved by the FDA, and highlighted the 2-hour cross-clamp time plus wide-ranging risk factors.

“I’m a surgeon and I voted no on all three counts,” said Murray H. Kwon, MD, Ronald Reagan University of California, Los Angeles Medical Center. “As far as risk/benefit, if it was just limited to one group – the 4-hour plus – I would say yes, but if you’re going to tell me that there’s a risk/benefit for the 2-hour with the alcoholic, I don’t know how that was proved in anything.”

Dr. Kwon was also troubled by lack of proper controls and by the one quarter of patients who ended up on mechanical circulatory support in the first 30 days after transplant. “I find that highly aberrant.”

Joaquin E. Cigarroa, MD, head of cardiovascular medicine, Oregon Health & Science University, Portland, said the unmet need for patients with refractory, end-stage heart failure is challenging and quite emotional, but also voted no across the board, citing concerns about a lack of comparator in the EXPAND trials and overall out-of-body ischemic time.

“As it relates to risk/benefit, I thought long and hard about voting yes despite all the unknowns because of this emotion, but ultimately I voted no because of the secondary 2-hours plus alcoholism, diabetes, or minor coronary disease, in which the ischemic burden and ongoing lactate production concern me,” he said.

Although the panel decision is nonbinding, there was strong support from the committee members for a randomized, postapproval trial and more complete animal studies.

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

After more than 10 hours of intense debate, a Food and Drug Administration advisory panel gave its support to a premarket approval application (PMA) for the TransMedics Organ Care System (OCS) Heart system.

Courtesy Transmedics

The OCS Heart is a portable extracorporeal perfusion and monitoring system designed to keep a donor heart in a normothermic, beating state. The “heart in a box” technology allows donor hearts to be transported across longer distances than is possible with standard cold storage, which can safely preserve donor hearts for about 4 hours.

The Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 12 to 5, with 1 abstention, that the benefits of the OCS Heart System outweigh its risks.

The panel voted in favor of the OCS Heart being effective (10 yes, 6 no, and 2 abstaining) and safe (9 yes, 7 no, 2 abstaining) but not without mixed feelings.

James Blankenship, MD, a cardiologist at the University of New Mexico, Albuquerque, voted yes to all three questions but said: “If it had been compared to standard of care, I would have voted no to all three. But if it’s compared to getting an [left ventricular assist device] LVAD or not getting a heart at all, I would say the benefits outweigh the risks.”

Marc R. Katz, MD, chief of cardiothoracic surgery, Medical University of South Carolina, Charleston, also gave universal support, noting that the rate of heart transplantations has been flat for years. “This is a big step forward toward being able to expand that number. Now all that said, it obviously was a less-than-perfect study and I do think there needs to be some constraints put on the utilization.”

The panel reviewed data from the single-arm OCS Heart EXPAND trial and associated EXPAND Continued Access Protocol (CAP), as well the sponsor’s first OCS Heart trial, PROCEED II.

EXPAND met its effectiveness endpoint, with 88% of donor hearts successfully transplanted, an 8% incidence of severe primary graft dysfunction (PGD) 24 hours after transplantation, and 94.6% survival at 30 days.

Data from 41 patients with 30-day follow-up in the ongoing EXPAND CAP show 91% of donor hearts were utilized, a 2.4% incidence of severe PGD, and 100% 30-day survival.

The sponsor and the FDA clashed over changes made to the trial after the PMA was submitted, the appropriateness of the effectiveness outcome, and claims by the FDA that there was substantial overlap in demographic characteristics between the extended criteria donor hearts in the EXPAND trials and the standard criteria donor hearts in PROCEED II.

TransMedics previously submitted a PMA based on PROCEED II but it noted in submitted documents that it was withdrawn because of “fundamental disagreements with FDA” on the interpretation of a post hoc analysis with United Network for Organ Sharing registry data that identified increased all-cause mortality risk but comparable cardiac-related mortality in patients with OCS hearts.

During the marathon hearing, FDA officials presented several post hoc analyses, including one stratified by donor inclusion criteria, in which 30-day survival estimates were worse in recipients of single-criterion organs than for those receiving donor organs with multiple inclusion criteria (85% vs. 91.4%). In a second analysis, 2-year point estimates of survival also trended lower with donor organs having only one extended criterion.

Reported EXPAND CAP 6- and 12-month survival estimates were 100% and 93%, respectively, which was higher than EXPAND (93% and 84%), but there was substantial censoring (>50%) at 6 months and beyond, FDA officials said.

When EXPAND and CAP data were pooled, modeled survival curves shifted upward but there was a substantial site effect, with a single site contributing 46% of data, which may affect generalizability of the results, they noted.

“I voted yes for safety, no for efficacy, and no for approval and I’d just like to say I found this to be the most difficult vote in my experience on this panel,” John Hirshfeld, MD, University of Pennsylvania, Philadelphia, said. “I was very concerned that the PROCEED data suggests a possible harm, and in the absence of an interpretable comparator for the EXPAND trial, it’s really not possible to decide if there’s efficacy.”

Keith B. Allen, MD, director of surgical research at Saint Luke’s Hospital of Kansas City (Mo.), said, “I voted no on safety; I’m not going to give the company a pass. I think their animal data was sorely lacking and a lot of issues over the last 10 years could have been addressed with some key animal studies.

“For efficacy and risk/benefit, I voted yes for both,” he said. “Had this been standard of care and only PROCEED II, I would have voted no, but I do think there are a lot of hearts that go in the bucket and this is a challenging population.”

More than a dozen physicians and patients spoke at the open public hearing about the potential for the device to expand donor heart utilization, including a recipient whose own father died while waiting on the transplant list. Only about 3 out of every 10 donated hearts are used for transplant. To ensure fair access, particularly for patients in rural areas, federal changes in 2020 mandate that organs be allocated to the sickest patients first.

Data showed that the OCS Heart System was associated with shorter waiting list times, compared with U.S. averages but longer preservation times than cold static preservation.

In all, 13% of accepted donor organs were subsequently turned down after OCS heart preservation. Lactate levels were cited as the principal reason for turn-down but, FDA officials said, the validity of using lactate as a marker for transplantability is unclear.

Pathologic analysis of OCS Heart turned-down donor hearts with stable antemortem hemodynamics, normal or near-normal anatomy and normal ventricular function by echocardiography, and autopsy findings of acute diffuse or multifocal myocardial damage “suggest that in an important proportion of cases the OCS Heart system did not provide effective organ preservation or its use caused severe myocardial damage to what might have been an acceptable graft for transplant,” said Andrew Farb, MD, chief medical officer of the FDA’s Office of Cardiovascular Devices.
 

Proposed indication

In the present PMA, the OCS Heart System is indicated for donor hearts with one or more of the following characteristics: an expected cross-clamp or ischemic time of at least 4 hours because of donor or recipient characteristics; or an expected total cross-clamp time of at least 2 hours plus one of the following risk factors: donor age 55 or older, history of cardiac arrest and downtime of at least 20 minutes, history of alcoholism, history of diabetes, donor ejection fraction of 40%-50%,history of left ventricular hypertrophy, and donor angiogram with luminal irregularities but no significant coronary artery disease

Several members voiced concern about “indication creep” should the device be approved by the FDA, and highlighted the 2-hour cross-clamp time plus wide-ranging risk factors.

“I’m a surgeon and I voted no on all three counts,” said Murray H. Kwon, MD, Ronald Reagan University of California, Los Angeles Medical Center. “As far as risk/benefit, if it was just limited to one group – the 4-hour plus – I would say yes, but if you’re going to tell me that there’s a risk/benefit for the 2-hour with the alcoholic, I don’t know how that was proved in anything.”

Dr. Kwon was also troubled by lack of proper controls and by the one quarter of patients who ended up on mechanical circulatory support in the first 30 days after transplant. “I find that highly aberrant.”

Joaquin E. Cigarroa, MD, head of cardiovascular medicine, Oregon Health & Science University, Portland, said the unmet need for patients with refractory, end-stage heart failure is challenging and quite emotional, but also voted no across the board, citing concerns about a lack of comparator in the EXPAND trials and overall out-of-body ischemic time.

“As it relates to risk/benefit, I thought long and hard about voting yes despite all the unknowns because of this emotion, but ultimately I voted no because of the secondary 2-hours plus alcoholism, diabetes, or minor coronary disease, in which the ischemic burden and ongoing lactate production concern me,” he said.

Although the panel decision is nonbinding, there was strong support from the committee members for a randomized, postapproval trial and more complete animal studies.

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

Adults with knee osteoarthritis (OA) who participated in a self-directed, web-based exercise program with automated text-message reminders and encouragement for 6 months showed significant improvement in overall knee pain and physical function, compared with patients who received web-based OA information alone, in a randomized trial of 180 individuals.

copyright Nandyphotos/Thinkstock

The results support a role for web-based exercise intervention to improve knee OA patients’ access to recommended exercises and to assist clinicians in managing patients on a population level, according to the first author of the study, Rachel Kate Nelligan, of the University of Melbourne, and colleagues. Their report is in JAMA Internal Medicine.

“Our free-to-access, unsupervised program could serve as an entry-level intervention, with participants who do not experience clinical benefits progressing to subsequent steps for more intensive, personalized management,” they said. “Such an approach has the potential to better distribute limited health care resources and reduce demand for contact with health professionals, thus improving access for those requiring it.”

Only two other randomized, clinical trials have evaluated web-based interventions for OA without contact from health professionals, according to the authors. While one of those did not find any differences in outcomes at 4 months when comparing a self-directed progressive lower-limb strength, flexibility, and walking program to being on a wait list, a separate trial evaluating a 9-module physical activity program in adults with knee and/or hip OA vs. a wait-list control group found evidence for efficacy for physical function at 3 months, but not quality of life or function in sport and recreation.

For the current study, researchers recruited 206 adults in Australia with clinically diagnosed knee OA via online advertisements and a volunteer database. Participants were aged 45 years or older, and reported activity-related knee pain and morning knee stiffness lasting at least 30 minutes; knee pain on most days for at least 3 months; and average knee pain severity of 4 or higher on an 11-point numeric rating scale in the previous week. In addition, participants were required to own a cell phone with text messaging, have Internet access, and be able to complete assessments.

Patients randomized to the intervention of the My Knee Exercise website received web-based information about OA and the value of exercise, with a 24-week self-directed program of strengthening exercises plus automated text messages to motivate behavior changes and encourage adherence to the exercise program. Controls received access to web-based information about OA and the value of exercise, but without the prescribed exercises or texts. Patients in the intervention group received an average of 60 text messages during the study period, and the average reply rate was 73%.

The primary study outcomes were changes in overall knee pain based on a numeric 0-10 rating scale and changes in physical function based on the Western Ontario and McMaster Universities Osteoarthritis Index 0-68 scale. A total of 180 participants completed both primary outcome measures at 24 weeks. The average age of the participants was 60 years, and 61% were women.

After 24 weeks, the intervention group averaged significantly greater improvement of 1.6 units for overall knee pain (P < .001) and 5.2 units for physical function (P = .002), compared with controls.

In addition, the proportion of patients who exceeded the minimal clinically important difference in pain improvement of at least 1.8 units was significantly higher in the intervention group, compared with controls (72.1% vs. 42.0%; P < .001). Similarly, more intervention-group patients achieved the minimal clinically important difference in WOMAC physical function of improvement of at least 6 units (68.0% vs. 40.8%; P < .001).

Secondary outcomes included additional measures of knee pain, knee function for sport and recreation, quality of life, physical activity, self-efficacy, overall improvement, and treatment satisfaction. Between-group differences favored the intervention on most measures, including Knee Injury and Osteoarthritis Outcome Score subscales for pain, sports/recreation, and quality of life; health-related quality of life; Arthritis Self-Efficacy Scale (ASES) pain subscale, individual change since baseline, and overall patient satisfaction. “Changes in PASE [Physical Activity Scale for the Elderly], ASES function, and SEE [Self Efficacy Exercise] were similar in both groups,” the researchers said.

No serious adverse events were reported by any study participants. Eight patients in the intervention group reported knee pain during the study, compared with one of the controls, and use of pain medications was similar between the groups, except that more control participants used massage, heat or cold, and topical anti-inflammatories.

The results suggest that a majority of participants in the intervention group improved pain and function without the need for in-person contact with a health professional, the researchers noted. However, more intensive management may be needed to support the 30% who did not benefit from the unsupervised approach, they said.

The study findings were limited by several factors, including the potential bias of a volunteer study population, possible lack of generalizability to individuals with lower levels of education or self-efficacy, and lack of direct comparison between web-based intervention and clinician-delivered intervention, the researchers noted.

The study was funded by the National Health and Medical Research Council, whose fellowships supported two of the authors. Lead author Ms. Nelligan disclosed a PhD scholarship from the Australian Government Research Training Program and personal fees from the University of Melbourne unrelated to the current study.

Adults with knee osteoarthritis (OA) who participated in a self-directed, web-based exercise program with automated text-message reminders and encouragement for 6 months showed significant improvement in overall knee pain and physical function, compared with patients who received web-based OA information alone, in a randomized trial of 180 individuals.

copyright Nandyphotos/Thinkstock

The results support a role for web-based exercise intervention to improve knee OA patients’ access to recommended exercises and to assist clinicians in managing patients on a population level, according to the first author of the study, Rachel Kate Nelligan, of the University of Melbourne, and colleagues. Their report is in JAMA Internal Medicine.

“Our free-to-access, unsupervised program could serve as an entry-level intervention, with participants who do not experience clinical benefits progressing to subsequent steps for more intensive, personalized management,” they said. “Such an approach has the potential to better distribute limited health care resources and reduce demand for contact with health professionals, thus improving access for those requiring it.”

Only two other randomized, clinical trials have evaluated web-based interventions for OA without contact from health professionals, according to the authors. While one of those did not find any differences in outcomes at 4 months when comparing a self-directed progressive lower-limb strength, flexibility, and walking program to being on a wait list, a separate trial evaluating a 9-module physical activity program in adults with knee and/or hip OA vs. a wait-list control group found evidence for efficacy for physical function at 3 months, but not quality of life or function in sport and recreation.

For the current study, researchers recruited 206 adults in Australia with clinically diagnosed knee OA via online advertisements and a volunteer database. Participants were aged 45 years or older, and reported activity-related knee pain and morning knee stiffness lasting at least 30 minutes; knee pain on most days for at least 3 months; and average knee pain severity of 4 or higher on an 11-point numeric rating scale in the previous week. In addition, participants were required to own a cell phone with text messaging, have Internet access, and be able to complete assessments.

Patients randomized to the intervention of the My Knee Exercise website received web-based information about OA and the value of exercise, with a 24-week self-directed program of strengthening exercises plus automated text messages to motivate behavior changes and encourage adherence to the exercise program. Controls received access to web-based information about OA and the value of exercise, but without the prescribed exercises or texts. Patients in the intervention group received an average of 60 text messages during the study period, and the average reply rate was 73%.

The primary study outcomes were changes in overall knee pain based on a numeric 0-10 rating scale and changes in physical function based on the Western Ontario and McMaster Universities Osteoarthritis Index 0-68 scale. A total of 180 participants completed both primary outcome measures at 24 weeks. The average age of the participants was 60 years, and 61% were women.

After 24 weeks, the intervention group averaged significantly greater improvement of 1.6 units for overall knee pain (P < .001) and 5.2 units for physical function (P = .002), compared with controls.

In addition, the proportion of patients who exceeded the minimal clinically important difference in pain improvement of at least 1.8 units was significantly higher in the intervention group, compared with controls (72.1% vs. 42.0%; P < .001). Similarly, more intervention-group patients achieved the minimal clinically important difference in WOMAC physical function of improvement of at least 6 units (68.0% vs. 40.8%; P < .001).

Secondary outcomes included additional measures of knee pain, knee function for sport and recreation, quality of life, physical activity, self-efficacy, overall improvement, and treatment satisfaction. Between-group differences favored the intervention on most measures, including Knee Injury and Osteoarthritis Outcome Score subscales for pain, sports/recreation, and quality of life; health-related quality of life; Arthritis Self-Efficacy Scale (ASES) pain subscale, individual change since baseline, and overall patient satisfaction. “Changes in PASE [Physical Activity Scale for the Elderly], ASES function, and SEE [Self Efficacy Exercise] were similar in both groups,” the researchers said.

No serious adverse events were reported by any study participants. Eight patients in the intervention group reported knee pain during the study, compared with one of the controls, and use of pain medications was similar between the groups, except that more control participants used massage, heat or cold, and topical anti-inflammatories.

The results suggest that a majority of participants in the intervention group improved pain and function without the need for in-person contact with a health professional, the researchers noted. However, more intensive management may be needed to support the 30% who did not benefit from the unsupervised approach, they said.

The study findings were limited by several factors, including the potential bias of a volunteer study population, possible lack of generalizability to individuals with lower levels of education or self-efficacy, and lack of direct comparison between web-based intervention and clinician-delivered intervention, the researchers noted.

The study was funded by the National Health and Medical Research Council, whose fellowships supported two of the authors. Lead author Ms. Nelligan disclosed a PhD scholarship from the Australian Government Research Training Program and personal fees from the University of Melbourne unrelated to the current study.

Adults with knee osteoarthritis (OA) who participated in a self-directed, web-based exercise program with automated text-message reminders and encouragement for 6 months showed significant improvement in overall knee pain and physical function, compared with patients who received web-based OA information alone, in a randomized trial of 180 individuals.

copyright Nandyphotos/Thinkstock

The results support a role for web-based exercise intervention to improve knee OA patients’ access to recommended exercises and to assist clinicians in managing patients on a population level, according to the first author of the study, Rachel Kate Nelligan, of the University of Melbourne, and colleagues. Their report is in JAMA Internal Medicine.

“Our free-to-access, unsupervised program could serve as an entry-level intervention, with participants who do not experience clinical benefits progressing to subsequent steps for more intensive, personalized management,” they said. “Such an approach has the potential to better distribute limited health care resources and reduce demand for contact with health professionals, thus improving access for those requiring it.”

Only two other randomized, clinical trials have evaluated web-based interventions for OA without contact from health professionals, according to the authors. While one of those did not find any differences in outcomes at 4 months when comparing a self-directed progressive lower-limb strength, flexibility, and walking program to being on a wait list, a separate trial evaluating a 9-module physical activity program in adults with knee and/or hip OA vs. a wait-list control group found evidence for efficacy for physical function at 3 months, but not quality of life or function in sport and recreation.

For the current study, researchers recruited 206 adults in Australia with clinically diagnosed knee OA via online advertisements and a volunteer database. Participants were aged 45 years or older, and reported activity-related knee pain and morning knee stiffness lasting at least 30 minutes; knee pain on most days for at least 3 months; and average knee pain severity of 4 or higher on an 11-point numeric rating scale in the previous week. In addition, participants were required to own a cell phone with text messaging, have Internet access, and be able to complete assessments.

Patients randomized to the intervention of the My Knee Exercise website received web-based information about OA and the value of exercise, with a 24-week self-directed program of strengthening exercises plus automated text messages to motivate behavior changes and encourage adherence to the exercise program. Controls received access to web-based information about OA and the value of exercise, but without the prescribed exercises or texts. Patients in the intervention group received an average of 60 text messages during the study period, and the average reply rate was 73%.

The primary study outcomes were changes in overall knee pain based on a numeric 0-10 rating scale and changes in physical function based on the Western Ontario and McMaster Universities Osteoarthritis Index 0-68 scale. A total of 180 participants completed both primary outcome measures at 24 weeks. The average age of the participants was 60 years, and 61% were women.

After 24 weeks, the intervention group averaged significantly greater improvement of 1.6 units for overall knee pain (P < .001) and 5.2 units for physical function (P = .002), compared with controls.

In addition, the proportion of patients who exceeded the minimal clinically important difference in pain improvement of at least 1.8 units was significantly higher in the intervention group, compared with controls (72.1% vs. 42.0%; P < .001). Similarly, more intervention-group patients achieved the minimal clinically important difference in WOMAC physical function of improvement of at least 6 units (68.0% vs. 40.8%; P < .001).

Secondary outcomes included additional measures of knee pain, knee function for sport and recreation, quality of life, physical activity, self-efficacy, overall improvement, and treatment satisfaction. Between-group differences favored the intervention on most measures, including Knee Injury and Osteoarthritis Outcome Score subscales for pain, sports/recreation, and quality of life; health-related quality of life; Arthritis Self-Efficacy Scale (ASES) pain subscale, individual change since baseline, and overall patient satisfaction. “Changes in PASE [Physical Activity Scale for the Elderly], ASES function, and SEE [Self Efficacy Exercise] were similar in both groups,” the researchers said.

No serious adverse events were reported by any study participants. Eight patients in the intervention group reported knee pain during the study, compared with one of the controls, and use of pain medications was similar between the groups, except that more control participants used massage, heat or cold, and topical anti-inflammatories.

The results suggest that a majority of participants in the intervention group improved pain and function without the need for in-person contact with a health professional, the researchers noted. However, more intensive management may be needed to support the 30% who did not benefit from the unsupervised approach, they said.

The study findings were limited by several factors, including the potential bias of a volunteer study population, possible lack of generalizability to individuals with lower levels of education or self-efficacy, and lack of direct comparison between web-based intervention and clinician-delivered intervention, the researchers noted.

The study was funded by the National Health and Medical Research Council, whose fellowships supported two of the authors. Lead author Ms. Nelligan disclosed a PhD scholarship from the Australian Government Research Training Program and personal fees from the University of Melbourne unrelated to the current study.

Separation anxiety plays a substantial role in suicidality in patients with mood and anxiety disorders, new research suggests.

Results of a study that included 500 outpatients with mood or anxiety disorders showed adult separation anxiety disorder (ASAD) was more frequent in patients with suicidal thoughts versus those who did not have the disorder. In addition, depression and separation anxiety also significantly predicted lifetime suicide risk.

“This study indicates a substantial role of separation anxiety in predicting suicidal thoughts, both as state-related symptoms ... and as longitudinal dimension symptoms,” say the investigators, led by Stefano Pini, MD, of the department of clinical and experimental medicine, section of psychiatry, University of Pisa (Italy).

“Greater understanding of the influence of separation anxiety in patients with affective disorders may encourage personalized interventions for reducing suicide risk,” they add.

The study was published in the March/April issue of the Journal of Clinical Psychiatry.
 

Frequently underdiagnosed

The authors describe a “close link between suicidal behaviors and interpersonal difficulties extending beyond the traditional approach of comprehending suicide as a phenomenon mainly related to depression.”

Previous research indicates that insecure adult attachment style might be associated with a greater likelihood of suicidal thoughts and attempts, and there might be an association between individual abnormal attachment sensitivity and suicide.

“Suicidal ideation or suicide attempts may be associated with disturbances in attachment, which may lead not only to a devastating experience of losing the feeling of interdependence and closeness but also to a rejection of life itself,” the authors suggest.

ASAD may be a “key factor” in understanding the relationship between individual attachment sensitivity to separation and suicidality.

An ASAD diagnosis was traditionally reserved for children and adolescents, but DSM-5 expanded the diagnosis to include adults over 18 years of age because research had “found a later onset to be common,” spanning the life course, even in the absence of a history of separation anxiety in childhood.

“Separation anxiety is an important clinical dimension, often with roots in childhood, but likely to manifest across the lifespan,” the authors note, adding that it is “frequently underdiagnosed.”

The relationship between ASAD and suicidality has not been explored extensively, so the researchers set out to examine the association.

The study included 509 consecutively recruited adult psychiatric outpatients with mood or anxiety disorders as a principle diagnosis.

Participants completed an array of scales, including item 3 on the Hamilton Depression Rating Scale (HDRS), which measures suicidality, as well as the Mood Spectrum Self-Report (MOODS-SR), a questionnaire evaluating lifetime suicidal symptoms.

Three scales were used to measure separation anxiety disorder: The Structured Interview for Separation Anxiety Symptoms in Adulthood/Childhood (SCI-SAS-A/C); the Separation Anxiety Symptom Inventory (SASI); and the Adult Separation Anxiety Scale (ASA-27).
 

Waxing and waning

Of the total sample, 215 patients were diagnosed with separation anxiety disorder (mean age at onset 15 years). Of the total sample, 19.9% scored ≥ 1 on the HDRS item 3, indicating the presence of suicidality.

Patients with suicidal thoughts more frequently experienced ASAD, compared with those without suicidal thoughts (53.6% vs. 39.6%, respectively, P = .01).

“All measures of adult as well as childhood separation anxiety were significantly elevated in the group of patients with current suicidality, based on HDRS item 3,” the authors report.

Logistic regression found that ASAD, major depression, bipolar I, and bipolar II disorders all predicted suicidal thoughts.

A linear regression model found that depression (P = .001) and ASA-27 separation anxiety (P = .001) significantly predicted lifetime suicide risk, based on the MOODS-SR scale.

In addition, “mediation analysis showed that, besides a direct effect, there is also an indirect effect of depression severity on the MOODS-SR suicidality score through the ASA-27 score, indicating that separation anxiety may act as an important mediating factor in the relationship between depression and suicidality,” the authors state.

The authors observe that separation anxiety “is an important clinical dimension, often with roots in childhood, but likely to wax and wane across the lifespan and even to manifest for the first time during adulthood.”
 

Treatment target?

Commenting on the study for this news organization, Megan Rogers, PhD, postdoctoral research fellow, Mount Sinai Beth Israel, New York, said the findings “point to symptoms of separation anxiety as a potential indicator of suicidal ideation, and should these findings be replicated and extended through longitudinal research, it suggests that symptoms of separation anxiety may be a relevant treatment target in certain populations to mitigate suicide risk.”

Dr. Rogers, who is the student division director at the American Association of Suicidology and was not involved with the study, said she thinks that studies of suicide have focused more on “individual symptoms of separation anxiety, such as excessive worry about loved ones or distress when anticipating separation from loved ones, rather than on separation anxiety as a categorical diagnosis.”

However, the study has an important take-home message for practicing clinicians, Dr. Rogers said. “In individuals with separation anxiety disorders, particularly those with comorbid mood conditions, it may be worth conducting a more thorough assessment of suicide risk, given the possibility of elevated suicidality in these patients.”

The study was supported in part by the German Research Foundation and the Fondazione Cassa di Risparmio di la Spezia. The authors and Dr. Rogers have disclosed no relevant financial relationships.

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

Separation anxiety plays a substantial role in suicidality in patients with mood and anxiety disorders, new research suggests.

Results of a study that included 500 outpatients with mood or anxiety disorders showed adult separation anxiety disorder (ASAD) was more frequent in patients with suicidal thoughts versus those who did not have the disorder. In addition, depression and separation anxiety also significantly predicted lifetime suicide risk.

“This study indicates a substantial role of separation anxiety in predicting suicidal thoughts, both as state-related symptoms ... and as longitudinal dimension symptoms,” say the investigators, led by Stefano Pini, MD, of the department of clinical and experimental medicine, section of psychiatry, University of Pisa (Italy).

“Greater understanding of the influence of separation anxiety in patients with affective disorders may encourage personalized interventions for reducing suicide risk,” they add.

The study was published in the March/April issue of the Journal of Clinical Psychiatry.
 

Frequently underdiagnosed

The authors describe a “close link between suicidal behaviors and interpersonal difficulties extending beyond the traditional approach of comprehending suicide as a phenomenon mainly related to depression.”

Previous research indicates that insecure adult attachment style might be associated with a greater likelihood of suicidal thoughts and attempts, and there might be an association between individual abnormal attachment sensitivity and suicide.

“Suicidal ideation or suicide attempts may be associated with disturbances in attachment, which may lead not only to a devastating experience of losing the feeling of interdependence and closeness but also to a rejection of life itself,” the authors suggest.

ASAD may be a “key factor” in understanding the relationship between individual attachment sensitivity to separation and suicidality.

An ASAD diagnosis was traditionally reserved for children and adolescents, but DSM-5 expanded the diagnosis to include adults over 18 years of age because research had “found a later onset to be common,” spanning the life course, even in the absence of a history of separation anxiety in childhood.

“Separation anxiety is an important clinical dimension, often with roots in childhood, but likely to manifest across the lifespan,” the authors note, adding that it is “frequently underdiagnosed.”

The relationship between ASAD and suicidality has not been explored extensively, so the researchers set out to examine the association.

The study included 509 consecutively recruited adult psychiatric outpatients with mood or anxiety disorders as a principle diagnosis.

Participants completed an array of scales, including item 3 on the Hamilton Depression Rating Scale (HDRS), which measures suicidality, as well as the Mood Spectrum Self-Report (MOODS-SR), a questionnaire evaluating lifetime suicidal symptoms.

Three scales were used to measure separation anxiety disorder: The Structured Interview for Separation Anxiety Symptoms in Adulthood/Childhood (SCI-SAS-A/C); the Separation Anxiety Symptom Inventory (SASI); and the Adult Separation Anxiety Scale (ASA-27).
 

Waxing and waning

Of the total sample, 215 patients were diagnosed with separation anxiety disorder (mean age at onset 15 years). Of the total sample, 19.9% scored ≥ 1 on the HDRS item 3, indicating the presence of suicidality.

Patients with suicidal thoughts more frequently experienced ASAD, compared with those without suicidal thoughts (53.6% vs. 39.6%, respectively, P = .01).

“All measures of adult as well as childhood separation anxiety were significantly elevated in the group of patients with current suicidality, based on HDRS item 3,” the authors report.

Logistic regression found that ASAD, major depression, bipolar I, and bipolar II disorders all predicted suicidal thoughts.

A linear regression model found that depression (P = .001) and ASA-27 separation anxiety (P = .001) significantly predicted lifetime suicide risk, based on the MOODS-SR scale.

In addition, “mediation analysis showed that, besides a direct effect, there is also an indirect effect of depression severity on the MOODS-SR suicidality score through the ASA-27 score, indicating that separation anxiety may act as an important mediating factor in the relationship between depression and suicidality,” the authors state.

The authors observe that separation anxiety “is an important clinical dimension, often with roots in childhood, but likely to wax and wane across the lifespan and even to manifest for the first time during adulthood.”
 

Treatment target?

Commenting on the study for this news organization, Megan Rogers, PhD, postdoctoral research fellow, Mount Sinai Beth Israel, New York, said the findings “point to symptoms of separation anxiety as a potential indicator of suicidal ideation, and should these findings be replicated and extended through longitudinal research, it suggests that symptoms of separation anxiety may be a relevant treatment target in certain populations to mitigate suicide risk.”

Dr. Rogers, who is the student division director at the American Association of Suicidology and was not involved with the study, said she thinks that studies of suicide have focused more on “individual symptoms of separation anxiety, such as excessive worry about loved ones or distress when anticipating separation from loved ones, rather than on separation anxiety as a categorical diagnosis.”

However, the study has an important take-home message for practicing clinicians, Dr. Rogers said. “In individuals with separation anxiety disorders, particularly those with comorbid mood conditions, it may be worth conducting a more thorough assessment of suicide risk, given the possibility of elevated suicidality in these patients.”

The study was supported in part by the German Research Foundation and the Fondazione Cassa di Risparmio di la Spezia. The authors and Dr. Rogers have disclosed no relevant financial relationships.

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

Separation anxiety plays a substantial role in suicidality in patients with mood and anxiety disorders, new research suggests.

Results of a study that included 500 outpatients with mood or anxiety disorders showed adult separation anxiety disorder (ASAD) was more frequent in patients with suicidal thoughts versus those who did not have the disorder. In addition, depression and separation anxiety also significantly predicted lifetime suicide risk.

“This study indicates a substantial role of separation anxiety in predicting suicidal thoughts, both as state-related symptoms ... and as longitudinal dimension symptoms,” say the investigators, led by Stefano Pini, MD, of the department of clinical and experimental medicine, section of psychiatry, University of Pisa (Italy).

“Greater understanding of the influence of separation anxiety in patients with affective disorders may encourage personalized interventions for reducing suicide risk,” they add.

The study was published in the March/April issue of the Journal of Clinical Psychiatry.
 

Frequently underdiagnosed

The authors describe a “close link between suicidal behaviors and interpersonal difficulties extending beyond the traditional approach of comprehending suicide as a phenomenon mainly related to depression.”

Previous research indicates that insecure adult attachment style might be associated with a greater likelihood of suicidal thoughts and attempts, and there might be an association between individual abnormal attachment sensitivity and suicide.

“Suicidal ideation or suicide attempts may be associated with disturbances in attachment, which may lead not only to a devastating experience of losing the feeling of interdependence and closeness but also to a rejection of life itself,” the authors suggest.

ASAD may be a “key factor” in understanding the relationship between individual attachment sensitivity to separation and suicidality.

An ASAD diagnosis was traditionally reserved for children and adolescents, but DSM-5 expanded the diagnosis to include adults over 18 years of age because research had “found a later onset to be common,” spanning the life course, even in the absence of a history of separation anxiety in childhood.

“Separation anxiety is an important clinical dimension, often with roots in childhood, but likely to manifest across the lifespan,” the authors note, adding that it is “frequently underdiagnosed.”

The relationship between ASAD and suicidality has not been explored extensively, so the researchers set out to examine the association.

The study included 509 consecutively recruited adult psychiatric outpatients with mood or anxiety disorders as a principle diagnosis.

Participants completed an array of scales, including item 3 on the Hamilton Depression Rating Scale (HDRS), which measures suicidality, as well as the Mood Spectrum Self-Report (MOODS-SR), a questionnaire evaluating lifetime suicidal symptoms.

Three scales were used to measure separation anxiety disorder: The Structured Interview for Separation Anxiety Symptoms in Adulthood/Childhood (SCI-SAS-A/C); the Separation Anxiety Symptom Inventory (SASI); and the Adult Separation Anxiety Scale (ASA-27).
 

Waxing and waning

Of the total sample, 215 patients were diagnosed with separation anxiety disorder (mean age at onset 15 years). Of the total sample, 19.9% scored ≥ 1 on the HDRS item 3, indicating the presence of suicidality.

Patients with suicidal thoughts more frequently experienced ASAD, compared with those without suicidal thoughts (53.6% vs. 39.6%, respectively, P = .01).

“All measures of adult as well as childhood separation anxiety were significantly elevated in the group of patients with current suicidality, based on HDRS item 3,” the authors report.

Logistic regression found that ASAD, major depression, bipolar I, and bipolar II disorders all predicted suicidal thoughts.

A linear regression model found that depression (P = .001) and ASA-27 separation anxiety (P = .001) significantly predicted lifetime suicide risk, based on the MOODS-SR scale.

In addition, “mediation analysis showed that, besides a direct effect, there is also an indirect effect of depression severity on the MOODS-SR suicidality score through the ASA-27 score, indicating that separation anxiety may act as an important mediating factor in the relationship between depression and suicidality,” the authors state.

The authors observe that separation anxiety “is an important clinical dimension, often with roots in childhood, but likely to wax and wane across the lifespan and even to manifest for the first time during adulthood.”
 

Treatment target?

Commenting on the study for this news organization, Megan Rogers, PhD, postdoctoral research fellow, Mount Sinai Beth Israel, New York, said the findings “point to symptoms of separation anxiety as a potential indicator of suicidal ideation, and should these findings be replicated and extended through longitudinal research, it suggests that symptoms of separation anxiety may be a relevant treatment target in certain populations to mitigate suicide risk.”

Dr. Rogers, who is the student division director at the American Association of Suicidology and was not involved with the study, said she thinks that studies of suicide have focused more on “individual symptoms of separation anxiety, such as excessive worry about loved ones or distress when anticipating separation from loved ones, rather than on separation anxiety as a categorical diagnosis.”

However, the study has an important take-home message for practicing clinicians, Dr. Rogers said. “In individuals with separation anxiety disorders, particularly those with comorbid mood conditions, it may be worth conducting a more thorough assessment of suicide risk, given the possibility of elevated suicidality in these patients.”

The study was supported in part by the German Research Foundation and the Fondazione Cassa di Risparmio di la Spezia. The authors and Dr. Rogers have disclosed no relevant financial relationships.

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

Loss of smell, loss of taste, dyspnea, and fatigue are the four most common symptoms that health care professionals in Sweden report 8 months after mild COVID-19 illness, new evidence reveals.

Approximately 1 in 10 health care workers experience one or more moderate to severe symptoms that negatively affect their quality of life, according to the study.

Nenad Cavoski/Getty Images

“We see that a substantial portion of health care workers suffer from long-term symptoms after mild COVID-19,” senior author Charlotte Thålin, MD, PhD, said in an interview. She added that loss of smell and taste “may seem trivial, but have a negative impact on work, social, and home life in the long run.”

The study is noteworthy not only for tracking the COVID-19-related experiences of health care workers over time, but also for what it did not find. There was no increased prevalence of cognitive issues – including memory or concentration – that others have linked to what’s often called long-haul COVID-19.

The research letter was published online April 7, 2021, in JAMA.

“Even if you are young and previously healthy, a mild COVID-19 infection may result in long-term consequences,” said Dr. Thålin, from the department of clinical sciences at Danderyd Hospital, Karolinska Institute, Stockholm.

The researchers did not observe an increased risk for long-term symptoms after asymptomatic COVID-19.
 

Adding to existing evidence

This research letter “adds to the growing body of literature showing that people recovering from COVID have reported a diverse array of symptoms lasting for months after initial infection,” Lekshmi Santhosh, MD, said in an interview. She is physician faculty lead at the University of California, San Francisco Post-COVID OPTIMAL Clinic.

Previous research revealed severe long-term symptoms, including heart palpitations and neurologic impairments, among people hospitalized with COVID-19. However, “there is limited data on the long-term effects after mild COVID-19, and these studies are often hampered by selection bias and without proper control groups,” Dr. Thålin said.

The absence of these more severe symptoms after mild COVID-19 is “reassuring,” she added.

The current findings are part of the ongoing COMMUNITY (COVID-19 Biomarker and Immunity) study looking at long-term immunity. Health care professionals enrolled in the research between April 15 and May 8, 2020, and have initial blood tests repeated every 4 months.

Dr. Thålin, lead author Sebastian Havervall, MD, and their colleagues compared symptom reporting between 323 hospital employees who had mild COVID-19 at least 8 months earlier with 1,072 employees who did not have COVID-19 throughout the study.

The results show that 26% of those who had COVID-19 previously had at least one moderate to severe symptom that lasted more than 2 months, compared with 9% in the control group.

The group with a history of mild COVID-19 was a median 43 years old and 83% were women. The controls were a median 47 years old and 86% were women.

“These data mirror what we have seen across long-term cohorts of patients with COVID-19 infection. Notably, mild illness among previously healthy individuals may be associated with long-term persistent symptoms,” Sarah Jolley, MD, a pulmonologist specializing in critical care at the University of Colorado Hospital in Aurora and director of the Post-COVID Clinic, said in an interview.

“In this cohort, similar to others, this seems to be more pronounced in women,” Dr. Jolley added.
 

Key findings on functioning

At 8 months, using a smartphone app, participants reported presence, duration, and severity of 23 predefined symptoms. Researchers used the Sheehan Disability Scale to gauge functional impairment.

A total of 11% participants reported at least one symptom that negatively affected work or social or home life at 8 months versus only 2% of the control group.

Seropositive participants were almost two times more likely to report that their long-term symptoms moderately to markedly disrupted their work life, 8% versus 4% of seronegative healthcare workers (relative risk, 1.8; 95%; confidence interval, 1.2-2.9).

Disruptions to a social life from long-term symptoms were 2.5 times more likely in the seropositive group. A total 15% of this cohort reported moderate to marked effects, compared with 6% of the seronegative group (RR, 2.5; 95% CI, 1.8-3.6).

The researchers also inquired about home life disruptions, which were reported by 12% of the seropositive health care workers and 5% of the seronegative participants (RR, 2.3; 95% CI, 1.6-3.4).

The study’s findings “tracks with a lot of the other work we’re seeing,” David Putrino, PT, PhD, director of rehabilitation innovation at Mount Sinai Health System in New York, said in an interview. He and his colleagues are responsible for managing the rehabilitation of patients with long COVID.

Interestingly, the proportion of people with persistent symptoms might be underestimated in this research, Dr. Putrino said. “Antibodies are not an entirely reliable biomarker. So what the researchers are using here is the most conservative measure of who may have had the virus.”

Potential recall bias and the subjective rating of symptoms were possible limitations of the study.

When asked to speculate why researchers did not find higher levels of cognitive dysfunction, Dr. Putrino said that self-reports are generally less reliable than measures like the Montreal Cognitive Assessment for detecting cognitive impairment.

Furthermore, unlike many of the people with long-haul COVID-19 whom he treats clinically – ones who are “really struggling” – the health care workers studied in Sweden are functioning well enough to perform their duties at the hospital, so the study population may not represent the population at large.
 

More research required

“More research needs to be conducted to investigate the mechanisms underlying these persistent symptoms, and several centers, including UCSF, are conducting research into why this might be,” Dr. Santhosh said.

Dr. Thålin and colleagues plan to continue following participants. “The primary aim of the COMMUNITY study is to investigate long-term immunity after COVID-19, but we will also look into possible underlying pathophysiological mechanisms behind COVID-19–related long-term symptoms,” she said.

“I hope to see that taste and smell will return,” Dr. Thålin added.

“We’re really just starting to understand the long-term effects of COVID-19,” Putrino said. “This is something we’re going to see a lot of moving forward.”

Dr. Thålin, Dr. Santhosh, Dr. Jolley, and Dr. Putrino disclosed no relevant financial relationships. The research was funded by grants from the Knut and Alice Wallenberg Foundation, Jonas and Christina af Jochnick Foundation, Leif Lundblad Family Foundation, Region Stockholm, and Erling-Persson Family Foundation.

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