Many women with hidradenitis suppurativa have pregnancy-related concerns that go unaddressed by their doctors, according to a study that surveyed 59 women with HS.

Previous studies have shown the potential for adverse pregnancy outcomes associated with inflammatory conditions such as systemic vasculitis and lupus, but such data on HS and pregnancy are limited, which makes patient counseling a challenge, Ademide A. Adelekun, MD, of the University of Pennsylvania, Philadelphia, and colleagues wrote.

In a research letter published in JAMA Dermatology, they reported their findings from an email survey of female patients at two academic dermatology departments. A total of 59 women responded to the survey; their average age was 32 years, the majority (76%) had Hurley stage II disease, and 29 (49%) reported having ever been pregnant.

Two of the 29 women (7%) were pregnant at the time of the study survey; 20 of the other 27 pregnant women (74%) said they had full-term births, 4 (15%) reported miscarriages, and 3 (11%) had undergone an abortion.

A total of five patients (9%) reported difficulty getting pregnant after 1 year, and seven (12%) reported undergoing fertility treatments.

Nearly three-quarters of the women (73%) reported that HS had a negative impact on their sexual health, and 54% said they wished their doctors provided more counseling on HS and pregnancy.

A total of 14 patients (24%) said they believed HS affected their ability to become pregnant because of either decreased sexual activity or decreased fertility caused by HS medications, and nearly half (49%) said they believed that discontinuing all HS medications during pregnancy was necessary for safety reasons.

Patients also expressed concern about the possible heritability of HS: 80% said that physicians had not counseled them about HS heritability and 68% expressed concern that their child would have HS.

In addition, 83% said they had not received information about the potential impact of HS on pregnancy, and 22%, or 13 women, were concerned that childbirth would be more difficult; 11 of these 13 women (85%) had HS that affected the vulva and groin, and 4 of the 8 women who reported concerns about difficulty breastfeeding had HS that involved the breast.

Of the 59 patients surveyed, 12 (20%) said they believed HS poses risks to the child, including through transmission of HS in 8 (67%) or through an infection during a vaginal delivery in 7 women (58%).

The prevalence of HS patients’ concerns about pregnancy “may have unfavorable implications for family planning and mental health and may play a role in the inadequate treatment of HS in patients who are pregnant or planning to become pregnant,” the authors noted. “Family planning and prenatal counseling are particularly critical for those with HS given that clinicians weigh the risks of medication use against the benefits of disease control, which is associated with improved pregnancy outcomes for those with inflammatory conditions.”

The study findings were limited by several factors including “recall bias, low response rate, use of a nonvalidated survey, and generalizability to nonacademic settings,” the researchers noted. However, the results emphasize the often-underrecognized concerns of women with HS and the need for improvements in pregnancy-related counseling and systematic evaluation of outcomes.

The researchers had no financial conflicts to disclose. This study was funded by a FOCUS Medical Student Fellowship in Women’s Health grant.

Many women with hidradenitis suppurativa have pregnancy-related concerns that go unaddressed by their doctors, according to a study that surveyed 59 women with HS.

Previous studies have shown the potential for adverse pregnancy outcomes associated with inflammatory conditions such as systemic vasculitis and lupus, but such data on HS and pregnancy are limited, which makes patient counseling a challenge, Ademide A. Adelekun, MD, of the University of Pennsylvania, Philadelphia, and colleagues wrote.

In a research letter published in JAMA Dermatology, they reported their findings from an email survey of female patients at two academic dermatology departments. A total of 59 women responded to the survey; their average age was 32 years, the majority (76%) had Hurley stage II disease, and 29 (49%) reported having ever been pregnant.

Two of the 29 women (7%) were pregnant at the time of the study survey; 20 of the other 27 pregnant women (74%) said they had full-term births, 4 (15%) reported miscarriages, and 3 (11%) had undergone an abortion.

A total of five patients (9%) reported difficulty getting pregnant after 1 year, and seven (12%) reported undergoing fertility treatments.

Nearly three-quarters of the women (73%) reported that HS had a negative impact on their sexual health, and 54% said they wished their doctors provided more counseling on HS and pregnancy.

A total of 14 patients (24%) said they believed HS affected their ability to become pregnant because of either decreased sexual activity or decreased fertility caused by HS medications, and nearly half (49%) said they believed that discontinuing all HS medications during pregnancy was necessary for safety reasons.

Patients also expressed concern about the possible heritability of HS: 80% said that physicians had not counseled them about HS heritability and 68% expressed concern that their child would have HS.

In addition, 83% said they had not received information about the potential impact of HS on pregnancy, and 22%, or 13 women, were concerned that childbirth would be more difficult; 11 of these 13 women (85%) had HS that affected the vulva and groin, and 4 of the 8 women who reported concerns about difficulty breastfeeding had HS that involved the breast.

Of the 59 patients surveyed, 12 (20%) said they believed HS poses risks to the child, including through transmission of HS in 8 (67%) or through an infection during a vaginal delivery in 7 women (58%).

The prevalence of HS patients’ concerns about pregnancy “may have unfavorable implications for family planning and mental health and may play a role in the inadequate treatment of HS in patients who are pregnant or planning to become pregnant,” the authors noted. “Family planning and prenatal counseling are particularly critical for those with HS given that clinicians weigh the risks of medication use against the benefits of disease control, which is associated with improved pregnancy outcomes for those with inflammatory conditions.”

The study findings were limited by several factors including “recall bias, low response rate, use of a nonvalidated survey, and generalizability to nonacademic settings,” the researchers noted. However, the results emphasize the often-underrecognized concerns of women with HS and the need for improvements in pregnancy-related counseling and systematic evaluation of outcomes.

The researchers had no financial conflicts to disclose. This study was funded by a FOCUS Medical Student Fellowship in Women’s Health grant.

Many women with hidradenitis suppurativa have pregnancy-related concerns that go unaddressed by their doctors, according to a study that surveyed 59 women with HS.

Previous studies have shown the potential for adverse pregnancy outcomes associated with inflammatory conditions such as systemic vasculitis and lupus, but such data on HS and pregnancy are limited, which makes patient counseling a challenge, Ademide A. Adelekun, MD, of the University of Pennsylvania, Philadelphia, and colleagues wrote.

In a research letter published in JAMA Dermatology, they reported their findings from an email survey of female patients at two academic dermatology departments. A total of 59 women responded to the survey; their average age was 32 years, the majority (76%) had Hurley stage II disease, and 29 (49%) reported having ever been pregnant.

Two of the 29 women (7%) were pregnant at the time of the study survey; 20 of the other 27 pregnant women (74%) said they had full-term births, 4 (15%) reported miscarriages, and 3 (11%) had undergone an abortion.

A total of five patients (9%) reported difficulty getting pregnant after 1 year, and seven (12%) reported undergoing fertility treatments.

Nearly three-quarters of the women (73%) reported that HS had a negative impact on their sexual health, and 54% said they wished their doctors provided more counseling on HS and pregnancy.

A total of 14 patients (24%) said they believed HS affected their ability to become pregnant because of either decreased sexual activity or decreased fertility caused by HS medications, and nearly half (49%) said they believed that discontinuing all HS medications during pregnancy was necessary for safety reasons.

Patients also expressed concern about the possible heritability of HS: 80% said that physicians had not counseled them about HS heritability and 68% expressed concern that their child would have HS.

In addition, 83% said they had not received information about the potential impact of HS on pregnancy, and 22%, or 13 women, were concerned that childbirth would be more difficult; 11 of these 13 women (85%) had HS that affected the vulva and groin, and 4 of the 8 women who reported concerns about difficulty breastfeeding had HS that involved the breast.

Of the 59 patients surveyed, 12 (20%) said they believed HS poses risks to the child, including through transmission of HS in 8 (67%) or through an infection during a vaginal delivery in 7 women (58%).

The prevalence of HS patients’ concerns about pregnancy “may have unfavorable implications for family planning and mental health and may play a role in the inadequate treatment of HS in patients who are pregnant or planning to become pregnant,” the authors noted. “Family planning and prenatal counseling are particularly critical for those with HS given that clinicians weigh the risks of medication use against the benefits of disease control, which is associated with improved pregnancy outcomes for those with inflammatory conditions.”

The study findings were limited by several factors including “recall bias, low response rate, use of a nonvalidated survey, and generalizability to nonacademic settings,” the researchers noted. However, the results emphasize the often-underrecognized concerns of women with HS and the need for improvements in pregnancy-related counseling and systematic evaluation of outcomes.

The researchers had no financial conflicts to disclose. This study was funded by a FOCUS Medical Student Fellowship in Women’s Health grant.

As health care providers work against the clock to administer as many COVID-19 vaccine doses as soon as possible, logistics aren’t the only thing standing in their way.

Misinformation – which has hampered the nation’s coronavirus response – is now hurting vaccination efforts, too.

About one in five Americans say they won’t take a COVID-19 vaccine, according to the Kaiser Family Foundation’s COVID-19 Vaccine Monitor. Even a third of health care workers have voiced their hesitance.

The spread of COVID-19 vaccine misinformation creates “a really powerful parallel pandemic to the real pandemic,” Imran Ahmed, CEO of the Center for Countering Digital Hate, told NPR. The center has tracked the links between vaccine misinformation and vaccine hesitancy during the past year.

The “infodemic” is essentially “working in concert to really undermine our capacity to contain COVID,” Mr. Ahmed said.

To help combat vaccine misinformation and address lingering concerns that people have, corporate, nonprofit, and media leaders, including this news organization, are joining a public service campaign called VaxFacts. Led by HealthGuard, the goal of the campaign is to provide facts and tools to help consumers make informed decisions about vaccines.

Steven Brill, co-CEO of HealthGuard, said credible information that comes from trusted messengers is critical to counter vaccine hesitancy.

“There’s traditionally a lot of skepticism about vaccines. That has really ramped up in the last few years based on campaigns about the measles vaccine. ... And now you have the COVID vaccine, which by everybody’s understanding has been ‘rushed,’ ” Mr. Brill said during an interview on Coronavirus in Context, a video series hosted by John Whyte, MD, chief medical officer for WebMD.

“There may be less understanding of the nature of what rushed really means. It’s still gone through the clinical trials it needs to go through.”

HealthGuard is a browser extension that flags health hoaxes, provides credibility ratings for hundreds of websites, and guides users to sources that offer trusted information. The tool is a new service from NewsGuard, which veteran journalists Mr. Brill and co-CEO Gordon Crovitz created in 2018 to combat misinformation in the news. HealthGuard, which is free for users globally through June, is specifically aimed at informing readers about health myths related to vaccines and COVID-19. It will cost $35 per year after that.

The HealthGuard Coronavirus Tracking Center has flagged nearly 400 websites for publishing misinformation about the coronavirus, including several top myths about COVID-19 vaccines:

• The mRNA vaccines can alter human DNA.
• Vaccines will use microchip surveillance technology.
• COVID-19 vaccines cause infertility.
• The vaccine developed by Oxford University will turn people into monkeys.
• COVID-19 vaccines contain aborted human fetal tissue.

As a partner, this news organization will feature continuing coverage of COVID-19 vaccine misinformation, including articles and videos.

There will be other efforts this year. Google has launched a $3 million fund to back fact-checking organizations to counter vaccine misinformation, and social media platforms are monitoring posts that actively promote disinformation around vaccines.

The United States has distributed nearly 50 million vaccine doses, and states have administered more than 32 million of them, including 5.9 million second doses in the two-shot vaccines, according to the latest CDC update.

To reach herd immunity, about 75%-85% of Americans will need to receive a vaccine, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in December 2020.

Vaccine skepticism has increased in recent years, which has led to a decline in vaccination rates and the highest annual number of measles cases in the United States in more than 25 years, according to the Pew Research Center. In 2019, the World Health Organization named vaccine hesitancy as 1 of 10 threats to global health.

With the COVID-19 vaccines in particular, people have voiced concerns about their safety and how well they work, given their accelerated development, according to Kaiser’s poll. They’re also worried about potential side effects, the perceived role of politics in the development process, and a lack of trust in government. Others don’t trust vaccines in general or believe they may contract COVID-19 from a vaccine, the Kaiser poll found, “suggesting that messages combating particular types of misinformation may be especially important for increasing vaccine confidence.”

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

As health care providers work against the clock to administer as many COVID-19 vaccine doses as soon as possible, logistics aren’t the only thing standing in their way.

Misinformation – which has hampered the nation’s coronavirus response – is now hurting vaccination efforts, too.

About one in five Americans say they won’t take a COVID-19 vaccine, according to the Kaiser Family Foundation’s COVID-19 Vaccine Monitor. Even a third of health care workers have voiced their hesitance.

The spread of COVID-19 vaccine misinformation creates “a really powerful parallel pandemic to the real pandemic,” Imran Ahmed, CEO of the Center for Countering Digital Hate, told NPR. The center has tracked the links between vaccine misinformation and vaccine hesitancy during the past year.

The “infodemic” is essentially “working in concert to really undermine our capacity to contain COVID,” Mr. Ahmed said.

To help combat vaccine misinformation and address lingering concerns that people have, corporate, nonprofit, and media leaders, including this news organization, are joining a public service campaign called VaxFacts. Led by HealthGuard, the goal of the campaign is to provide facts and tools to help consumers make informed decisions about vaccines.

Steven Brill, co-CEO of HealthGuard, said credible information that comes from trusted messengers is critical to counter vaccine hesitancy.

“There’s traditionally a lot of skepticism about vaccines. That has really ramped up in the last few years based on campaigns about the measles vaccine. ... And now you have the COVID vaccine, which by everybody’s understanding has been ‘rushed,’ ” Mr. Brill said during an interview on Coronavirus in Context, a video series hosted by John Whyte, MD, chief medical officer for WebMD.

“There may be less understanding of the nature of what rushed really means. It’s still gone through the clinical trials it needs to go through.”

HealthGuard is a browser extension that flags health hoaxes, provides credibility ratings for hundreds of websites, and guides users to sources that offer trusted information. The tool is a new service from NewsGuard, which veteran journalists Mr. Brill and co-CEO Gordon Crovitz created in 2018 to combat misinformation in the news. HealthGuard, which is free for users globally through June, is specifically aimed at informing readers about health myths related to vaccines and COVID-19. It will cost $35 per year after that.

The HealthGuard Coronavirus Tracking Center has flagged nearly 400 websites for publishing misinformation about the coronavirus, including several top myths about COVID-19 vaccines:

• The mRNA vaccines can alter human DNA.
• Vaccines will use microchip surveillance technology.
• COVID-19 vaccines cause infertility.
• The vaccine developed by Oxford University will turn people into monkeys.
• COVID-19 vaccines contain aborted human fetal tissue.

As a partner, this news organization will feature continuing coverage of COVID-19 vaccine misinformation, including articles and videos.

There will be other efforts this year. Google has launched a $3 million fund to back fact-checking organizations to counter vaccine misinformation, and social media platforms are monitoring posts that actively promote disinformation around vaccines.

The United States has distributed nearly 50 million vaccine doses, and states have administered more than 32 million of them, including 5.9 million second doses in the two-shot vaccines, according to the latest CDC update.

To reach herd immunity, about 75%-85% of Americans will need to receive a vaccine, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in December 2020.

Vaccine skepticism has increased in recent years, which has led to a decline in vaccination rates and the highest annual number of measles cases in the United States in more than 25 years, according to the Pew Research Center. In 2019, the World Health Organization named vaccine hesitancy as 1 of 10 threats to global health.

With the COVID-19 vaccines in particular, people have voiced concerns about their safety and how well they work, given their accelerated development, according to Kaiser’s poll. They’re also worried about potential side effects, the perceived role of politics in the development process, and a lack of trust in government. Others don’t trust vaccines in general or believe they may contract COVID-19 from a vaccine, the Kaiser poll found, “suggesting that messages combating particular types of misinformation may be especially important for increasing vaccine confidence.”

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

As health care providers work against the clock to administer as many COVID-19 vaccine doses as soon as possible, logistics aren’t the only thing standing in their way.

Misinformation – which has hampered the nation’s coronavirus response – is now hurting vaccination efforts, too.

About one in five Americans say they won’t take a COVID-19 vaccine, according to the Kaiser Family Foundation’s COVID-19 Vaccine Monitor. Even a third of health care workers have voiced their hesitance.

The spread of COVID-19 vaccine misinformation creates “a really powerful parallel pandemic to the real pandemic,” Imran Ahmed, CEO of the Center for Countering Digital Hate, told NPR. The center has tracked the links between vaccine misinformation and vaccine hesitancy during the past year.

The “infodemic” is essentially “working in concert to really undermine our capacity to contain COVID,” Mr. Ahmed said.

To help combat vaccine misinformation and address lingering concerns that people have, corporate, nonprofit, and media leaders, including this news organization, are joining a public service campaign called VaxFacts. Led by HealthGuard, the goal of the campaign is to provide facts and tools to help consumers make informed decisions about vaccines.

Steven Brill, co-CEO of HealthGuard, said credible information that comes from trusted messengers is critical to counter vaccine hesitancy.

“There’s traditionally a lot of skepticism about vaccines. That has really ramped up in the last few years based on campaigns about the measles vaccine. ... And now you have the COVID vaccine, which by everybody’s understanding has been ‘rushed,’ ” Mr. Brill said during an interview on Coronavirus in Context, a video series hosted by John Whyte, MD, chief medical officer for WebMD.

“There may be less understanding of the nature of what rushed really means. It’s still gone through the clinical trials it needs to go through.”

HealthGuard is a browser extension that flags health hoaxes, provides credibility ratings for hundreds of websites, and guides users to sources that offer trusted information. The tool is a new service from NewsGuard, which veteran journalists Mr. Brill and co-CEO Gordon Crovitz created in 2018 to combat misinformation in the news. HealthGuard, which is free for users globally through June, is specifically aimed at informing readers about health myths related to vaccines and COVID-19. It will cost $35 per year after that.

The HealthGuard Coronavirus Tracking Center has flagged nearly 400 websites for publishing misinformation about the coronavirus, including several top myths about COVID-19 vaccines:

• The mRNA vaccines can alter human DNA.
• Vaccines will use microchip surveillance technology.
• COVID-19 vaccines cause infertility.
• The vaccine developed by Oxford University will turn people into monkeys.
• COVID-19 vaccines contain aborted human fetal tissue.

As a partner, this news organization will feature continuing coverage of COVID-19 vaccine misinformation, including articles and videos.

There will be other efforts this year. Google has launched a $3 million fund to back fact-checking organizations to counter vaccine misinformation, and social media platforms are monitoring posts that actively promote disinformation around vaccines.

The United States has distributed nearly 50 million vaccine doses, and states have administered more than 32 million of them, including 5.9 million second doses in the two-shot vaccines, according to the latest CDC update.

To reach herd immunity, about 75%-85% of Americans will need to receive a vaccine, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in December 2020.

Vaccine skepticism has increased in recent years, which has led to a decline in vaccination rates and the highest annual number of measles cases in the United States in more than 25 years, according to the Pew Research Center. In 2019, the World Health Organization named vaccine hesitancy as 1 of 10 threats to global health.

With the COVID-19 vaccines in particular, people have voiced concerns about their safety and how well they work, given their accelerated development, according to Kaiser’s poll. They’re also worried about potential side effects, the perceived role of politics in the development process, and a lack of trust in government. Others don’t trust vaccines in general or believe they may contract COVID-19 from a vaccine, the Kaiser poll found, “suggesting that messages combating particular types of misinformation may be especially important for increasing vaccine confidence.”

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

Outcomes for mechanically ventilated adults with sepsis receiving light sedation were the same whether they received dexmedetomidine or propofol, according to data from a 13-center randomized, controlled, double-blind study published online Feb. 2 in the New England Journal of Medicine.

Dexmedetomidine (an alpha2-receptor agonist) and propofol (a gamma-aminobutyric acid [GABA]–receptor agonist) have similar safety profiles.

The findings from the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure (MENDS2) trial were published on an accelerated schedule to coincide with the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Lead author Christopher G. Hughes, MD, chief of anesthesiology in critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization that previous trials have shown that dexmedetomidine is likely superior to benzodiazepines, especially in improving delirium, coma, and time on a ventilator. Until this trial, dexmedetomidine’s performance in a head-to-head comparison with propofol – the current standard-of-care agent – was not clear.

Researchers discovered that, “despite theoretical advantages of dexmedetomidine, that did not translate into the clinical realm when patients were receiving up-to-date sedation care,” he said.

Guidelines currently recommend either drug when light sedation is needed for adults on ventilators. The drugs are different in the way they affect arousability, immunity, and inflammation, but a comparison of outcomes in adults with sepsis – in terms of days alive without brain dysfunction – had never before been performed in a randomized, controlled trial.

In this trial, 422 patients were randomly assigned to receive either dexmedetomidine (0.15-1.5 mcg/kg of body weight per hour) or propofol (5-50 mcg/kg per minute). Doses were adjusted by bedside nurses (who were unblinded) to achieve specified sedation goals.

The primary outcome was days alive without delirium or coma in the 14 days of intervention. The researchers found no difference between the two groups (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval, 0.74-1.26).

There was also little difference in three secondary outcomes: ventilator-free days (adjusted median, 23.7 vs. 24.0 days; OR, 0.98); death at 90 days (38% vs. 39%; hazard ratio, 1.06); or the Telephone Interview for Cognitive Status (TICS) Total score measuring global cognition at 6 months (adjusted median score, 40.9 vs. 41.4; OR, 0.94).

Dr. Hughes said the researchers “specifically went with a high-severity-of-illness cohort that would be most likely to see an effect.”

He said the drugs have different adverse-effect profiles, so a clinician can consider those in deciding between the two, but either should be fine at baseline.

The researchers note that at least 20 million patients each year develop sepsis with severe organ dysfunction, and more than 20% receive mechanical ventilation.
 

Confirmation of current guidelines

Sandra Kane-Gill, PharmD, president-elect of SCCM, stated in an interview that she is impressed with the study design and said the results give definitive confirmation of current guidelines.

“The rigorous study design is different from previous comparative-effectiveness trials on the drugs in this group of patients,” she said.

As to what clinicians think about when choosing one over the other, Dr. Kane-Gill said that with dexmedetomidine, there may be more concern about bradycardia, whereas propofol may be associated with concerns of high triglycerides.

“There may be more comfort with use of propofol,” and dexmedetomidine can be more costly than propofol, she added, so those could be factors in decision-making as well.

Dr. Hughes said this study offers a robust look at cognition after the ICU, which is getting increasing attention.

“We had a much more extensive cognitive battery we performed on patients than in previous studies,” Dr. Hughes said, “and it’s important that we did not find a difference in either the main cognition or the other cognitive scores between the two agents.”

Enrollment was completed before the pandemic, but he said the results are relevant to COVID-19 patients because those who are on ventilators in the ICU are in a sick, septic-shock cohort.

“COVID patients would be the type of patients we enrolled in this study,” he said, “with the high severity of illness and the infection on top of being on a ventilator. We know that sedation regimens have been challenging in COVID patients.”

Dr. Hughes and Dr. Kane-Gill have disclosed no relevant financial relationships.

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

Outcomes for mechanically ventilated adults with sepsis receiving light sedation were the same whether they received dexmedetomidine or propofol, according to data from a 13-center randomized, controlled, double-blind study published online Feb. 2 in the New England Journal of Medicine.

Dexmedetomidine (an alpha2-receptor agonist) and propofol (a gamma-aminobutyric acid [GABA]–receptor agonist) have similar safety profiles.

The findings from the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure (MENDS2) trial were published on an accelerated schedule to coincide with the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Lead author Christopher G. Hughes, MD, chief of anesthesiology in critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization that previous trials have shown that dexmedetomidine is likely superior to benzodiazepines, especially in improving delirium, coma, and time on a ventilator. Until this trial, dexmedetomidine’s performance in a head-to-head comparison with propofol – the current standard-of-care agent – was not clear.

Researchers discovered that, “despite theoretical advantages of dexmedetomidine, that did not translate into the clinical realm when patients were receiving up-to-date sedation care,” he said.

Guidelines currently recommend either drug when light sedation is needed for adults on ventilators. The drugs are different in the way they affect arousability, immunity, and inflammation, but a comparison of outcomes in adults with sepsis – in terms of days alive without brain dysfunction – had never before been performed in a randomized, controlled trial.

In this trial, 422 patients were randomly assigned to receive either dexmedetomidine (0.15-1.5 mcg/kg of body weight per hour) or propofol (5-50 mcg/kg per minute). Doses were adjusted by bedside nurses (who were unblinded) to achieve specified sedation goals.

The primary outcome was days alive without delirium or coma in the 14 days of intervention. The researchers found no difference between the two groups (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval, 0.74-1.26).

There was also little difference in three secondary outcomes: ventilator-free days (adjusted median, 23.7 vs. 24.0 days; OR, 0.98); death at 90 days (38% vs. 39%; hazard ratio, 1.06); or the Telephone Interview for Cognitive Status (TICS) Total score measuring global cognition at 6 months (adjusted median score, 40.9 vs. 41.4; OR, 0.94).

Dr. Hughes said the researchers “specifically went with a high-severity-of-illness cohort that would be most likely to see an effect.”

He said the drugs have different adverse-effect profiles, so a clinician can consider those in deciding between the two, but either should be fine at baseline.

The researchers note that at least 20 million patients each year develop sepsis with severe organ dysfunction, and more than 20% receive mechanical ventilation.
 

Confirmation of current guidelines

Sandra Kane-Gill, PharmD, president-elect of SCCM, stated in an interview that she is impressed with the study design and said the results give definitive confirmation of current guidelines.

“The rigorous study design is different from previous comparative-effectiveness trials on the drugs in this group of patients,” she said.

As to what clinicians think about when choosing one over the other, Dr. Kane-Gill said that with dexmedetomidine, there may be more concern about bradycardia, whereas propofol may be associated with concerns of high triglycerides.

“There may be more comfort with use of propofol,” and dexmedetomidine can be more costly than propofol, she added, so those could be factors in decision-making as well.

Dr. Hughes said this study offers a robust look at cognition after the ICU, which is getting increasing attention.

“We had a much more extensive cognitive battery we performed on patients than in previous studies,” Dr. Hughes said, “and it’s important that we did not find a difference in either the main cognition or the other cognitive scores between the two agents.”

Enrollment was completed before the pandemic, but he said the results are relevant to COVID-19 patients because those who are on ventilators in the ICU are in a sick, septic-shock cohort.

“COVID patients would be the type of patients we enrolled in this study,” he said, “with the high severity of illness and the infection on top of being on a ventilator. We know that sedation regimens have been challenging in COVID patients.”

Dr. Hughes and Dr. Kane-Gill have disclosed no relevant financial relationships.

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

Outcomes for mechanically ventilated adults with sepsis receiving light sedation were the same whether they received dexmedetomidine or propofol, according to data from a 13-center randomized, controlled, double-blind study published online Feb. 2 in the New England Journal of Medicine.

Dexmedetomidine (an alpha2-receptor agonist) and propofol (a gamma-aminobutyric acid [GABA]–receptor agonist) have similar safety profiles.

The findings from the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure (MENDS2) trial were published on an accelerated schedule to coincide with the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Lead author Christopher G. Hughes, MD, chief of anesthesiology in critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization that previous trials have shown that dexmedetomidine is likely superior to benzodiazepines, especially in improving delirium, coma, and time on a ventilator. Until this trial, dexmedetomidine’s performance in a head-to-head comparison with propofol – the current standard-of-care agent – was not clear.

Researchers discovered that, “despite theoretical advantages of dexmedetomidine, that did not translate into the clinical realm when patients were receiving up-to-date sedation care,” he said.

Guidelines currently recommend either drug when light sedation is needed for adults on ventilators. The drugs are different in the way they affect arousability, immunity, and inflammation, but a comparison of outcomes in adults with sepsis – in terms of days alive without brain dysfunction – had never before been performed in a randomized, controlled trial.

In this trial, 422 patients were randomly assigned to receive either dexmedetomidine (0.15-1.5 mcg/kg of body weight per hour) or propofol (5-50 mcg/kg per minute). Doses were adjusted by bedside nurses (who were unblinded) to achieve specified sedation goals.

The primary outcome was days alive without delirium or coma in the 14 days of intervention. The researchers found no difference between the two groups (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval, 0.74-1.26).

There was also little difference in three secondary outcomes: ventilator-free days (adjusted median, 23.7 vs. 24.0 days; OR, 0.98); death at 90 days (38% vs. 39%; hazard ratio, 1.06); or the Telephone Interview for Cognitive Status (TICS) Total score measuring global cognition at 6 months (adjusted median score, 40.9 vs. 41.4; OR, 0.94).

Dr. Hughes said the researchers “specifically went with a high-severity-of-illness cohort that would be most likely to see an effect.”

He said the drugs have different adverse-effect profiles, so a clinician can consider those in deciding between the two, but either should be fine at baseline.

The researchers note that at least 20 million patients each year develop sepsis with severe organ dysfunction, and more than 20% receive mechanical ventilation.
 

Confirmation of current guidelines

Sandra Kane-Gill, PharmD, president-elect of SCCM, stated in an interview that she is impressed with the study design and said the results give definitive confirmation of current guidelines.

“The rigorous study design is different from previous comparative-effectiveness trials on the drugs in this group of patients,” she said.

As to what clinicians think about when choosing one over the other, Dr. Kane-Gill said that with dexmedetomidine, there may be more concern about bradycardia, whereas propofol may be associated with concerns of high triglycerides.

“There may be more comfort with use of propofol,” and dexmedetomidine can be more costly than propofol, she added, so those could be factors in decision-making as well.

Dr. Hughes said this study offers a robust look at cognition after the ICU, which is getting increasing attention.

“We had a much more extensive cognitive battery we performed on patients than in previous studies,” Dr. Hughes said, “and it’s important that we did not find a difference in either the main cognition or the other cognitive scores between the two agents.”

Enrollment was completed before the pandemic, but he said the results are relevant to COVID-19 patients because those who are on ventilators in the ICU are in a sick, septic-shock cohort.

“COVID patients would be the type of patients we enrolled in this study,” he said, “with the high severity of illness and the infection on top of being on a ventilator. We know that sedation regimens have been challenging in COVID patients.”

Dr. Hughes and Dr. Kane-Gill have disclosed no relevant financial relationships.

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

Bimekizumab, an experimental biologic for the treatment of psoriasis that inhibits both interleukin-17A and IL-17F, achieves rates of skin clearance greater than those reported in phase 3 trials with other biologics, according to data from two simultaneously published trials, one of which was a head-to-head comparison with ustekinumab.

In the head-to-head trial called BE VIVID, which included a placebo arm, there was a large advantage of bimekizumab over ustekinumab, a biologic that targets IL-12 and IL-23 and is approved for treating psoriasis, for both coprimary endpoints, according to a multinational group of investigators led by Kristian Reich, MD, PhD, professor of dermatology at the University Medical Center, Hamburg-Eppendorf, Germany.

The proportion of patients with skin clearance was not only greater but faster, “with responses observed after one dose,” Dr. Reich and coinvestigators reported.

The data from the BE VIVID trial was published simultaneously with the BE READY trial, which was placebo-controlled but did not include an active comparator.

Evaluated at week 16, the coprimary endpoints in both studies were skin clearance as measured by a Psoriasis Area Severity Index greater than 90% (PASI 90) and Investigators Global Assessment (IGA) score of 0 (clear) or 1 (almost clear).

In BE VIVID, 567 patients were randomized in 11 countries, including the United States. The dose of bimekizumab was 320 mg administered subcutaneously every 4 weeks. In a randomization scheme of 4:2:1, half as many patients (163) were randomized to ustekinumab (Stelara), which was administered in weight-based dosing of 45 mg or 90 mg at enrollment, at 4 weeks, and then every 12 weeks. The placebo arm had 83 patients. All were switched to bimekizumab at 16 weeks.

At week 16, PASI 90 was achieved in 85% of patients randomized to bimekizumab, compared with 50% of patients randomized to ustekinumab (P < .0001). The rate in the placebo group was 5%.

The bimekizumab advantage for an IGA response of 0 or 1 was of similar magnitude, relative to ustekinumab (84% vs. 53%; P < .0001) and placebo (5%). All secondary efficacy endpoints, such as PASI 90 at week 12 (85% vs. 44%) and PASI 100 at week 16 (59% vs. 21%), favored bimekizumab over ustekinumab.

In the BE READY trial, which evaluated the same dose and schedule of bimekizumab, the rates of PASI 90 at week 16 were 91% and 1% (P < .0001) for the experimental arm and placebo, respectively. The proportion of patients with an IGA score of 0 or 1 were 93% and 1% (P < .0001), respectively.

In BE READY, patients who achieved PASI 90 at week 16 were reallocated to receive bimekizumab every 4 weeks, bimekizumab every 8 weeks (also 320 mg), or placebo. Both schedules of bimekizumab maintained responses through week 56, according to the authors, led by Kenneth B. Gordon, MD, professor and chair of dermatology, Medical College of Wisconsin, Milwaukee.

In both trials, safety was evaluated over the first 16 weeks as well as over a subsequent maintenance period, which extended to 52 weeks in BE VIVID and 56 weeks in BE READY. For bimekizumab, oral candidiasis was the most common treatment-related adverse event. In BE VIVID, this adverse event was reported in 9% of bimekizumab patients, compared with 0% of either the ustekinumab or placebo groups, up to week 16. Out to week 52, the rates were 15% in the bimekizumab group and 1% in the ustekinumab group.

In the BE READY trial, the rates of oral candidiasis were 6% and 0% for bimekizumab and placebo, respectively, through week 16. Over the maintenance periods, the rates were 9% and 11% for the every-8-week and every-4-week doses, respectively.

Discontinuation for adverse events was not higher on bimekizumab than placebo in either trial, nor was the proportion of serious treatment-emergent adverse events.

Nevertheless, the potential for adverse events was a key part of the discussion regarding the future role of bimekizumab, if approved, in an editorial that accompanied the publication of these studies.

“Bimekizumab might be our most effective biologic for psoriasis yet,” coauthors, William W. Huang, MD, PhD, associate professor of dermatology, and Steven R. Feldman, MD, PhD, professor of dermatology, both at Wake Forest University, Winston-Salem, NC, wrote in the editorial. “If the goal of psoriasis treatment is complete clearance, bimekizumab seems like a good option from an efficacy perspective.”

However, they noted that other IL-17 blockers, like secukinumab (Cosentyx) and brodalumab (Siliq), have been associated with risks, including the development of inflammatory bowel disease. In addition to the oral candidiasis seen in the BE VIVID and BE READY trials, they cautioned that other issues might arise with longer follow-up and greater numbers of patients exposed to this therapy.

In an interview, Dr. Feldman said adequately informed patients might be willing to accept these risks for the potential of greater efficacy, but he emphasized the need for appropriate warnings and education.

“We have a lot of very good treatments that offer patients an excellent chance of an excellent outcome – treatments that have been around and in use in large numbers of people for years,” Dr. Feldman said. “Unless the doctor and patient felt strongly about the need to use this new, perhaps more potent option, I would be personally inclined to use treatment with well-established safety profiles first.”

The senior author of the BE VIVID trial, Mark Lebwohl, MD, dean for clinical therapeutics and professor of dermatology, at the Icahn School of Medicine at Mount Sinai, New York, disagreed. He acknowledged that other agents targeting IL-17 have been associated with IBD, but risk of IBD is already elevated in patients with psoriasis and the risk appears to be lower with bimekizumab relative to prior agents in this class.

“Bimekizumab has now been studied in thousands of patients over several years. We can say with support from a sizable amount of data that IBD is very uncommon,” he said. While oral candidiasis is associated with bimekizumab, it is “easy to treat.”

Asked specifically if he will consider using bimekizumab as a first-line agent in psoriasis patients who are candidates for a biologic, Dr. Lebwohl said he would. Based on the evidence that this agent is more effective than other options and has manageable side effects, he believes it will be an important new treatment option.

Dr. Reich, Dr. Lebwohl, Dr. Gordon, and Dr. Feldman have financial relationships with multiple companies that produce therapies for psoriasis, including UCB Pharma, the sponsor of these studies.
 

Bimekizumab, an experimental biologic for the treatment of psoriasis that inhibits both interleukin-17A and IL-17F, achieves rates of skin clearance greater than those reported in phase 3 trials with other biologics, according to data from two simultaneously published trials, one of which was a head-to-head comparison with ustekinumab.

In the head-to-head trial called BE VIVID, which included a placebo arm, there was a large advantage of bimekizumab over ustekinumab, a biologic that targets IL-12 and IL-23 and is approved for treating psoriasis, for both coprimary endpoints, according to a multinational group of investigators led by Kristian Reich, MD, PhD, professor of dermatology at the University Medical Center, Hamburg-Eppendorf, Germany.

The proportion of patients with skin clearance was not only greater but faster, “with responses observed after one dose,” Dr. Reich and coinvestigators reported.

The data from the BE VIVID trial was published simultaneously with the BE READY trial, which was placebo-controlled but did not include an active comparator.

Evaluated at week 16, the coprimary endpoints in both studies were skin clearance as measured by a Psoriasis Area Severity Index greater than 90% (PASI 90) and Investigators Global Assessment (IGA) score of 0 (clear) or 1 (almost clear).

In BE VIVID, 567 patients were randomized in 11 countries, including the United States. The dose of bimekizumab was 320 mg administered subcutaneously every 4 weeks. In a randomization scheme of 4:2:1, half as many patients (163) were randomized to ustekinumab (Stelara), which was administered in weight-based dosing of 45 mg or 90 mg at enrollment, at 4 weeks, and then every 12 weeks. The placebo arm had 83 patients. All were switched to bimekizumab at 16 weeks.

At week 16, PASI 90 was achieved in 85% of patients randomized to bimekizumab, compared with 50% of patients randomized to ustekinumab (P < .0001). The rate in the placebo group was 5%.

The bimekizumab advantage for an IGA response of 0 or 1 was of similar magnitude, relative to ustekinumab (84% vs. 53%; P < .0001) and placebo (5%). All secondary efficacy endpoints, such as PASI 90 at week 12 (85% vs. 44%) and PASI 100 at week 16 (59% vs. 21%), favored bimekizumab over ustekinumab.

In the BE READY trial, which evaluated the same dose and schedule of bimekizumab, the rates of PASI 90 at week 16 were 91% and 1% (P < .0001) for the experimental arm and placebo, respectively. The proportion of patients with an IGA score of 0 or 1 were 93% and 1% (P < .0001), respectively.

In BE READY, patients who achieved PASI 90 at week 16 were reallocated to receive bimekizumab every 4 weeks, bimekizumab every 8 weeks (also 320 mg), or placebo. Both schedules of bimekizumab maintained responses through week 56, according to the authors, led by Kenneth B. Gordon, MD, professor and chair of dermatology, Medical College of Wisconsin, Milwaukee.

In both trials, safety was evaluated over the first 16 weeks as well as over a subsequent maintenance period, which extended to 52 weeks in BE VIVID and 56 weeks in BE READY. For bimekizumab, oral candidiasis was the most common treatment-related adverse event. In BE VIVID, this adverse event was reported in 9% of bimekizumab patients, compared with 0% of either the ustekinumab or placebo groups, up to week 16. Out to week 52, the rates were 15% in the bimekizumab group and 1% in the ustekinumab group.

In the BE READY trial, the rates of oral candidiasis were 6% and 0% for bimekizumab and placebo, respectively, through week 16. Over the maintenance periods, the rates were 9% and 11% for the every-8-week and every-4-week doses, respectively.

Discontinuation for adverse events was not higher on bimekizumab than placebo in either trial, nor was the proportion of serious treatment-emergent adverse events.

Nevertheless, the potential for adverse events was a key part of the discussion regarding the future role of bimekizumab, if approved, in an editorial that accompanied the publication of these studies.

“Bimekizumab might be our most effective biologic for psoriasis yet,” coauthors, William W. Huang, MD, PhD, associate professor of dermatology, and Steven R. Feldman, MD, PhD, professor of dermatology, both at Wake Forest University, Winston-Salem, NC, wrote in the editorial. “If the goal of psoriasis treatment is complete clearance, bimekizumab seems like a good option from an efficacy perspective.”

However, they noted that other IL-17 blockers, like secukinumab (Cosentyx) and brodalumab (Siliq), have been associated with risks, including the development of inflammatory bowel disease. In addition to the oral candidiasis seen in the BE VIVID and BE READY trials, they cautioned that other issues might arise with longer follow-up and greater numbers of patients exposed to this therapy.

In an interview, Dr. Feldman said adequately informed patients might be willing to accept these risks for the potential of greater efficacy, but he emphasized the need for appropriate warnings and education.

“We have a lot of very good treatments that offer patients an excellent chance of an excellent outcome – treatments that have been around and in use in large numbers of people for years,” Dr. Feldman said. “Unless the doctor and patient felt strongly about the need to use this new, perhaps more potent option, I would be personally inclined to use treatment with well-established safety profiles first.”

The senior author of the BE VIVID trial, Mark Lebwohl, MD, dean for clinical therapeutics and professor of dermatology, at the Icahn School of Medicine at Mount Sinai, New York, disagreed. He acknowledged that other agents targeting IL-17 have been associated with IBD, but risk of IBD is already elevated in patients with psoriasis and the risk appears to be lower with bimekizumab relative to prior agents in this class.

“Bimekizumab has now been studied in thousands of patients over several years. We can say with support from a sizable amount of data that IBD is very uncommon,” he said. While oral candidiasis is associated with bimekizumab, it is “easy to treat.”

Asked specifically if he will consider using bimekizumab as a first-line agent in psoriasis patients who are candidates for a biologic, Dr. Lebwohl said he would. Based on the evidence that this agent is more effective than other options and has manageable side effects, he believes it will be an important new treatment option.

Dr. Reich, Dr. Lebwohl, Dr. Gordon, and Dr. Feldman have financial relationships with multiple companies that produce therapies for psoriasis, including UCB Pharma, the sponsor of these studies.
 

Bimekizumab, an experimental biologic for the treatment of psoriasis that inhibits both interleukin-17A and IL-17F, achieves rates of skin clearance greater than those reported in phase 3 trials with other biologics, according to data from two simultaneously published trials, one of which was a head-to-head comparison with ustekinumab.

In the head-to-head trial called BE VIVID, which included a placebo arm, there was a large advantage of bimekizumab over ustekinumab, a biologic that targets IL-12 and IL-23 and is approved for treating psoriasis, for both coprimary endpoints, according to a multinational group of investigators led by Kristian Reich, MD, PhD, professor of dermatology at the University Medical Center, Hamburg-Eppendorf, Germany.

The proportion of patients with skin clearance was not only greater but faster, “with responses observed after one dose,” Dr. Reich and coinvestigators reported.

The data from the BE VIVID trial was published simultaneously with the BE READY trial, which was placebo-controlled but did not include an active comparator.

Evaluated at week 16, the coprimary endpoints in both studies were skin clearance as measured by a Psoriasis Area Severity Index greater than 90% (PASI 90) and Investigators Global Assessment (IGA) score of 0 (clear) or 1 (almost clear).

In BE VIVID, 567 patients were randomized in 11 countries, including the United States. The dose of bimekizumab was 320 mg administered subcutaneously every 4 weeks. In a randomization scheme of 4:2:1, half as many patients (163) were randomized to ustekinumab (Stelara), which was administered in weight-based dosing of 45 mg or 90 mg at enrollment, at 4 weeks, and then every 12 weeks. The placebo arm had 83 patients. All were switched to bimekizumab at 16 weeks.

At week 16, PASI 90 was achieved in 85% of patients randomized to bimekizumab, compared with 50% of patients randomized to ustekinumab (P < .0001). The rate in the placebo group was 5%.

The bimekizumab advantage for an IGA response of 0 or 1 was of similar magnitude, relative to ustekinumab (84% vs. 53%; P < .0001) and placebo (5%). All secondary efficacy endpoints, such as PASI 90 at week 12 (85% vs. 44%) and PASI 100 at week 16 (59% vs. 21%), favored bimekizumab over ustekinumab.

In the BE READY trial, which evaluated the same dose and schedule of bimekizumab, the rates of PASI 90 at week 16 were 91% and 1% (P < .0001) for the experimental arm and placebo, respectively. The proportion of patients with an IGA score of 0 or 1 were 93% and 1% (P < .0001), respectively.

In BE READY, patients who achieved PASI 90 at week 16 were reallocated to receive bimekizumab every 4 weeks, bimekizumab every 8 weeks (also 320 mg), or placebo. Both schedules of bimekizumab maintained responses through week 56, according to the authors, led by Kenneth B. Gordon, MD, professor and chair of dermatology, Medical College of Wisconsin, Milwaukee.

In both trials, safety was evaluated over the first 16 weeks as well as over a subsequent maintenance period, which extended to 52 weeks in BE VIVID and 56 weeks in BE READY. For bimekizumab, oral candidiasis was the most common treatment-related adverse event. In BE VIVID, this adverse event was reported in 9% of bimekizumab patients, compared with 0% of either the ustekinumab or placebo groups, up to week 16. Out to week 52, the rates were 15% in the bimekizumab group and 1% in the ustekinumab group.

In the BE READY trial, the rates of oral candidiasis were 6% and 0% for bimekizumab and placebo, respectively, through week 16. Over the maintenance periods, the rates were 9% and 11% for the every-8-week and every-4-week doses, respectively.

Discontinuation for adverse events was not higher on bimekizumab than placebo in either trial, nor was the proportion of serious treatment-emergent adverse events.

Nevertheless, the potential for adverse events was a key part of the discussion regarding the future role of bimekizumab, if approved, in an editorial that accompanied the publication of these studies.

“Bimekizumab might be our most effective biologic for psoriasis yet,” coauthors, William W. Huang, MD, PhD, associate professor of dermatology, and Steven R. Feldman, MD, PhD, professor of dermatology, both at Wake Forest University, Winston-Salem, NC, wrote in the editorial. “If the goal of psoriasis treatment is complete clearance, bimekizumab seems like a good option from an efficacy perspective.”

However, they noted that other IL-17 blockers, like secukinumab (Cosentyx) and brodalumab (Siliq), have been associated with risks, including the development of inflammatory bowel disease. In addition to the oral candidiasis seen in the BE VIVID and BE READY trials, they cautioned that other issues might arise with longer follow-up and greater numbers of patients exposed to this therapy.

In an interview, Dr. Feldman said adequately informed patients might be willing to accept these risks for the potential of greater efficacy, but he emphasized the need for appropriate warnings and education.

“We have a lot of very good treatments that offer patients an excellent chance of an excellent outcome – treatments that have been around and in use in large numbers of people for years,” Dr. Feldman said. “Unless the doctor and patient felt strongly about the need to use this new, perhaps more potent option, I would be personally inclined to use treatment with well-established safety profiles first.”

The senior author of the BE VIVID trial, Mark Lebwohl, MD, dean for clinical therapeutics and professor of dermatology, at the Icahn School of Medicine at Mount Sinai, New York, disagreed. He acknowledged that other agents targeting IL-17 have been associated with IBD, but risk of IBD is already elevated in patients with psoriasis and the risk appears to be lower with bimekizumab relative to prior agents in this class.

“Bimekizumab has now been studied in thousands of patients over several years. We can say with support from a sizable amount of data that IBD is very uncommon,” he said. While oral candidiasis is associated with bimekizumab, it is “easy to treat.”

Asked specifically if he will consider using bimekizumab as a first-line agent in psoriasis patients who are candidates for a biologic, Dr. Lebwohl said he would. Based on the evidence that this agent is more effective than other options and has manageable side effects, he believes it will be an important new treatment option.

Dr. Reich, Dr. Lebwohl, Dr. Gordon, and Dr. Feldman have financial relationships with multiple companies that produce therapies for psoriasis, including UCB Pharma, the sponsor of these studies.
 

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

A novel community-based testing model has shown promise for colorectal cancer (CRC) screening during the COVID-19 pandemic.

The model is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program, called Drive By Flu-FIT.

The original Flu-FIT program was designed to increase access to CRC screening by offering home FIT tests to patients at the time of their annual flu shots. The program has been shown to increase CRC screening in diverse populations.

Researchers wanted to determine if a drive-by version of Flu-FIT could counteract the decrease in CRC screening seen during the pandemic, so they conducted a pilot study.

“FIT-based CRC screening overcomes many of the challenges to colonoscopy-based screening due to COVID-19, [such as] not requiring an office visit, thereby overcoming workforce disruptions and many patient concerns,” explained investigator Armenta Washington of the University of Pennsylvania, Philadelphia.

Ms. Washington presented results with Drive By Flu-FIT at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S02-04).
 

About the study

The pilot study of Drive By Flu-FIT was conducted in collaboration with the Einstein Healthcare Network and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region.

The program enrolled community members into one of three Drive By Flu-FIT events, which took place between October and November 2020. Eligible participants were aged 45-75 years and at average risk for CRC.

Interested candidates completed eligibility, registration, and demographic questionnaires electronically prior to enrollment.

Patients who enrolled watched a 7-minute CRC educational video and completed two questionnaires – one on CRC screening knowledge and one on screening intentions – before and after watching the video.

At the events, participants remained in their cars while physicians in personal protective equipment provided instructions on how to use the FIT and how to return the completed test to a medical collection box, as well as answering questions. Participants also had the option to receive a flu vaccine at the event.
 

Results

Among 335 registered participants, 80 (23.9%) did not ultimately attend an event, and 63 (18.8%) were deemed ineligible.

So 192 patients attended a Drive By Flu-FIT event and received a FIT (57.3%). Patients with symptoms/signs and family history of CRC were referred for colonoscopy.

Among patients who received a FIT, the mean age was 58.9 years, 60.4% were female, 93.8% self-identified as Black, 1.6% self-identified as Hispanic, 15.5% were uninsured, and 54.6% had been previously screened for CRC.

The researchers found that scores on the knowledge questionnaire increased after the video intervention (P = .0006), as did the intention to screen scores (P = .007).

“Baseline knowledge about CRC was high, with the exception of four items related to risk factors, frequency of FIT, Lynch syndrome, and the relationship between physical activity and the risk for CRC,” Ms. Washington explained. “All knowledge scores increased after the video, except for one item related to the early discovery of CRC and its relationship to survival.”

Among the 192 participants who received a FIT, 38 (19.7%) did not return it, 141 (73.4%) had a negative FIT result, and 13 (6.7%) had a positive FIT result and were referred to colonoscopy. The colonoscopy results are pending.

“Overall, we believe that this research shows that a social-distanced, Drive By Flu-FIT program is feasible, acceptable, and effective in engaging the community in CRC education and screening during the COVID-19 pandemic,” Ms. Washington said.

During a live discussion, Ms. Washington also noted that most patients opted to receive both the FIT test and the flu vaccine.

“This was certainly great work, especially with the outreach that was done,” commented moderator Ana Maria Lopez, MD, of Sidney Kimmel Medical College, Philadelphia.

The researchers plan to use the results of this pilot study to test and evaluate a Drive By COVID-19 vaccine-FIT model in spring 2021.

Ms. Washington and Dr. Lopez disclosed no conflicts of interest. The study was supported by the National Cancer Institute.  The FITs were donated by Polymedco Inc., and the flu vaccines were donated by the Philadelphia Public Health Department.

A novel community-based testing model has shown promise for colorectal cancer (CRC) screening during the COVID-19 pandemic.

The model is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program, called Drive By Flu-FIT.

The original Flu-FIT program was designed to increase access to CRC screening by offering home FIT tests to patients at the time of their annual flu shots. The program has been shown to increase CRC screening in diverse populations.

Researchers wanted to determine if a drive-by version of Flu-FIT could counteract the decrease in CRC screening seen during the pandemic, so they conducted a pilot study.

“FIT-based CRC screening overcomes many of the challenges to colonoscopy-based screening due to COVID-19, [such as] not requiring an office visit, thereby overcoming workforce disruptions and many patient concerns,” explained investigator Armenta Washington of the University of Pennsylvania, Philadelphia.

Ms. Washington presented results with Drive By Flu-FIT at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S02-04).
 

About the study

The pilot study of Drive By Flu-FIT was conducted in collaboration with the Einstein Healthcare Network and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region.

The program enrolled community members into one of three Drive By Flu-FIT events, which took place between October and November 2020. Eligible participants were aged 45-75 years and at average risk for CRC.

Interested candidates completed eligibility, registration, and demographic questionnaires electronically prior to enrollment.

Patients who enrolled watched a 7-minute CRC educational video and completed two questionnaires – one on CRC screening knowledge and one on screening intentions – before and after watching the video.

At the events, participants remained in their cars while physicians in personal protective equipment provided instructions on how to use the FIT and how to return the completed test to a medical collection box, as well as answering questions. Participants also had the option to receive a flu vaccine at the event.
 

Results

Among 335 registered participants, 80 (23.9%) did not ultimately attend an event, and 63 (18.8%) were deemed ineligible.

So 192 patients attended a Drive By Flu-FIT event and received a FIT (57.3%). Patients with symptoms/signs and family history of CRC were referred for colonoscopy.

Among patients who received a FIT, the mean age was 58.9 years, 60.4% were female, 93.8% self-identified as Black, 1.6% self-identified as Hispanic, 15.5% were uninsured, and 54.6% had been previously screened for CRC.

The researchers found that scores on the knowledge questionnaire increased after the video intervention (P = .0006), as did the intention to screen scores (P = .007).

“Baseline knowledge about CRC was high, with the exception of four items related to risk factors, frequency of FIT, Lynch syndrome, and the relationship between physical activity and the risk for CRC,” Ms. Washington explained. “All knowledge scores increased after the video, except for one item related to the early discovery of CRC and its relationship to survival.”

Among the 192 participants who received a FIT, 38 (19.7%) did not return it, 141 (73.4%) had a negative FIT result, and 13 (6.7%) had a positive FIT result and were referred to colonoscopy. The colonoscopy results are pending.

“Overall, we believe that this research shows that a social-distanced, Drive By Flu-FIT program is feasible, acceptable, and effective in engaging the community in CRC education and screening during the COVID-19 pandemic,” Ms. Washington said.

During a live discussion, Ms. Washington also noted that most patients opted to receive both the FIT test and the flu vaccine.

“This was certainly great work, especially with the outreach that was done,” commented moderator Ana Maria Lopez, MD, of Sidney Kimmel Medical College, Philadelphia.

The researchers plan to use the results of this pilot study to test and evaluate a Drive By COVID-19 vaccine-FIT model in spring 2021.

Ms. Washington and Dr. Lopez disclosed no conflicts of interest. The study was supported by the National Cancer Institute.  The FITs were donated by Polymedco Inc., and the flu vaccines were donated by the Philadelphia Public Health Department.

A novel community-based testing model has shown promise for colorectal cancer (CRC) screening during the COVID-19 pandemic.

The model is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program, called Drive By Flu-FIT.

The original Flu-FIT program was designed to increase access to CRC screening by offering home FIT tests to patients at the time of their annual flu shots. The program has been shown to increase CRC screening in diverse populations.

Researchers wanted to determine if a drive-by version of Flu-FIT could counteract the decrease in CRC screening seen during the pandemic, so they conducted a pilot study.

“FIT-based CRC screening overcomes many of the challenges to colonoscopy-based screening due to COVID-19, [such as] not requiring an office visit, thereby overcoming workforce disruptions and many patient concerns,” explained investigator Armenta Washington of the University of Pennsylvania, Philadelphia.

Ms. Washington presented results with Drive By Flu-FIT at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S02-04).
 

About the study

The pilot study of Drive By Flu-FIT was conducted in collaboration with the Einstein Healthcare Network and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region.

The program enrolled community members into one of three Drive By Flu-FIT events, which took place between October and November 2020. Eligible participants were aged 45-75 years and at average risk for CRC.

Interested candidates completed eligibility, registration, and demographic questionnaires electronically prior to enrollment.

Patients who enrolled watched a 7-minute CRC educational video and completed two questionnaires – one on CRC screening knowledge and one on screening intentions – before and after watching the video.

At the events, participants remained in their cars while physicians in personal protective equipment provided instructions on how to use the FIT and how to return the completed test to a medical collection box, as well as answering questions. Participants also had the option to receive a flu vaccine at the event.
 

Results

Among 335 registered participants, 80 (23.9%) did not ultimately attend an event, and 63 (18.8%) were deemed ineligible.

So 192 patients attended a Drive By Flu-FIT event and received a FIT (57.3%). Patients with symptoms/signs and family history of CRC were referred for colonoscopy.

Among patients who received a FIT, the mean age was 58.9 years, 60.4% were female, 93.8% self-identified as Black, 1.6% self-identified as Hispanic, 15.5% were uninsured, and 54.6% had been previously screened for CRC.

The researchers found that scores on the knowledge questionnaire increased after the video intervention (P = .0006), as did the intention to screen scores (P = .007).

“Baseline knowledge about CRC was high, with the exception of four items related to risk factors, frequency of FIT, Lynch syndrome, and the relationship between physical activity and the risk for CRC,” Ms. Washington explained. “All knowledge scores increased after the video, except for one item related to the early discovery of CRC and its relationship to survival.”

Among the 192 participants who received a FIT, 38 (19.7%) did not return it, 141 (73.4%) had a negative FIT result, and 13 (6.7%) had a positive FIT result and were referred to colonoscopy. The colonoscopy results are pending.

“Overall, we believe that this research shows that a social-distanced, Drive By Flu-FIT program is feasible, acceptable, and effective in engaging the community in CRC education and screening during the COVID-19 pandemic,” Ms. Washington said.

During a live discussion, Ms. Washington also noted that most patients opted to receive both the FIT test and the flu vaccine.

“This was certainly great work, especially with the outreach that was done,” commented moderator Ana Maria Lopez, MD, of Sidney Kimmel Medical College, Philadelphia.

The researchers plan to use the results of this pilot study to test and evaluate a Drive By COVID-19 vaccine-FIT model in spring 2021.

Ms. Washington and Dr. Lopez disclosed no conflicts of interest. The study was supported by the National Cancer Institute.  The FITs were donated by Polymedco Inc., and the flu vaccines were donated by the Philadelphia Public Health Department.

The United States has now reported more than 450,000 COVID-19 deaths during the pandemic, adding 3,912 more on Wednesday, according to data from Johns Hopkins University.

Daily COVID-19 deaths still remain high in the United States, though they’ve decreased slightly from the peak of 4,466 deaths on Jan. 12.

The United States also reported more than 121,000 new COVID-19 cases on Wednesday, which is down from a peak of more than 300,000 new cases on Tuesday. In total, more than 26.5 million people in the United States have been diagnosed with COVID-19, making up a quarter of the 104.5 million cases reported worldwide.

The 7-day average for COVID-19 hospitalizations and deaths continues to decline, according to the COVID Tracking Project. The 7-day average for hospitalizations is around 96,500, and the 7-day average for deaths is about 3,000. With the exception of Vermont, all states and territories have reported declines or no changes in their hospitalizations and deaths.

“We have seen the 7-day average for new deaths decrease for over a week. At the same time, states are reporting an average of 3,000 people dying per day,” the COVID Tracking Project wrote in a post on Twitter. “The data is hopeful and devastating.”

More than 2.2 million COVID-19 deaths have been reported worldwide. The United States continues to report the most deaths, followed by Brazil with 227,500, Mexico with 161,200, and India with 154,700 deaths.

The U.S. COVID-19 death toll could reach 496,000-534,000 by the end of February, according to a new forecast by the CDC, which includes models from 36 national groups. Deaths will likely decrease during the next 4 weeks, with about 11,300-22,600 deaths possibly reported during the last week of February.

The 534,000 total would equal about 1 death for every minute of the pandemic, according to CNN, given that the first U.S. death was reported on Feb. 29 last year.

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

The United States has now reported more than 450,000 COVID-19 deaths during the pandemic, adding 3,912 more on Wednesday, according to data from Johns Hopkins University.

Daily COVID-19 deaths still remain high in the United States, though they’ve decreased slightly from the peak of 4,466 deaths on Jan. 12.

The United States also reported more than 121,000 new COVID-19 cases on Wednesday, which is down from a peak of more than 300,000 new cases on Tuesday. In total, more than 26.5 million people in the United States have been diagnosed with COVID-19, making up a quarter of the 104.5 million cases reported worldwide.

The 7-day average for COVID-19 hospitalizations and deaths continues to decline, according to the COVID Tracking Project. The 7-day average for hospitalizations is around 96,500, and the 7-day average for deaths is about 3,000. With the exception of Vermont, all states and territories have reported declines or no changes in their hospitalizations and deaths.

“We have seen the 7-day average for new deaths decrease for over a week. At the same time, states are reporting an average of 3,000 people dying per day,” the COVID Tracking Project wrote in a post on Twitter. “The data is hopeful and devastating.”

More than 2.2 million COVID-19 deaths have been reported worldwide. The United States continues to report the most deaths, followed by Brazil with 227,500, Mexico with 161,200, and India with 154,700 deaths.

The U.S. COVID-19 death toll could reach 496,000-534,000 by the end of February, according to a new forecast by the CDC, which includes models from 36 national groups. Deaths will likely decrease during the next 4 weeks, with about 11,300-22,600 deaths possibly reported during the last week of February.

The 534,000 total would equal about 1 death for every minute of the pandemic, according to CNN, given that the first U.S. death was reported on Feb. 29 last year.

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

The United States has now reported more than 450,000 COVID-19 deaths during the pandemic, adding 3,912 more on Wednesday, according to data from Johns Hopkins University.

Daily COVID-19 deaths still remain high in the United States, though they’ve decreased slightly from the peak of 4,466 deaths on Jan. 12.

The United States also reported more than 121,000 new COVID-19 cases on Wednesday, which is down from a peak of more than 300,000 new cases on Tuesday. In total, more than 26.5 million people in the United States have been diagnosed with COVID-19, making up a quarter of the 104.5 million cases reported worldwide.

The 7-day average for COVID-19 hospitalizations and deaths continues to decline, according to the COVID Tracking Project. The 7-day average for hospitalizations is around 96,500, and the 7-day average for deaths is about 3,000. With the exception of Vermont, all states and territories have reported declines or no changes in their hospitalizations and deaths.

“We have seen the 7-day average for new deaths decrease for over a week. At the same time, states are reporting an average of 3,000 people dying per day,” the COVID Tracking Project wrote in a post on Twitter. “The data is hopeful and devastating.”

More than 2.2 million COVID-19 deaths have been reported worldwide. The United States continues to report the most deaths, followed by Brazil with 227,500, Mexico with 161,200, and India with 154,700 deaths.

The U.S. COVID-19 death toll could reach 496,000-534,000 by the end of February, according to a new forecast by the CDC, which includes models from 36 national groups. Deaths will likely decrease during the next 4 weeks, with about 11,300-22,600 deaths possibly reported during the last week of February.

The 534,000 total would equal about 1 death for every minute of the pandemic, according to CNN, given that the first U.S. death was reported on Feb. 29 last year.

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

The early phase of the coronavirus disease 2019 (COVID-19) pandemic in the United Kingdom (UK) was characterized by uncertainty as clinicians grappled to understand and manage an unfamiliar disease that affected very high numbers of patients amid radically evolving working environments, with little evidence to support their efforts. Early reports indicated high mortality in patients hospitalized with COVID-19.

As the disease became better understood, treatment evolved and the mortality appears to have decreased. For example, two recent papers, a national study of critical care patients in the UK and a single-site study from New York, have demonstrated a significant reduction in adjusted mortality between the pre- and post-peak periods.^1,2 However, the UK study was restricted to patients receiving critical care, potentially introducing bias due to varying critical care admission thresholds over time, while the single-site US study may not be generalizable. Moreover, both studies measured only in-hospital mortality. It remains uncertain therefore whether overall mortality has decreased on a broad scale after accounting for changes in patient characteristics.

The aim of this study was to use a national dataset to assess the casemix-adjusted overall mortality trend in England over the first 5 months of the COVID-19 pandemic.

We conducted a retrospective, secondary analysis of English National Health Services (NHS) hospitals’ admissions of patients at least 18 years of age between March 1 and July 31, 2020. Data were obtained from the Hospital Episode Statistics (HES) admitted patient care dataset.³ This is an administrative dataset that contains data on diagnoses and procedures as well as organizational characteristics and patient demographics for all NHS activity in England. We included all patients with an International Statistical Classification of Diseases, Tenth Revision (ICD-10) diagnosis of U07.1 (COVID-19, virus identified) and U07.2 (COVID-19, virus not identified).

The primary outcome of death within 28 days of admission was obtained by linking to the Civil Registrations (Deaths) - Secondary Care Cut - Information dataset, which includes the date, place, and cause of death from the Office for National Statistics⁴ and which was complete through September 31, 2020. The time horizon of 28 days from admission was chosen to approximate the Public Health England definition of a death from COVID-19 as being within 28 days of testing positive.⁵ We restricted our analysis to emergency admissions of persons age >18 years. If a patient had multiple emergency admissions, we restricted our analysis to the first admission to ensure comparability across hospitalizations and to best represent outcomes from the earliest onset of COVID-19.

We estimated a modified Poisson regression⁶ to predict death at 28 days, with month of admission, region, source of admission, age, deprivation, gender, ethnic group, and the 29 comorbidities in the Elixhauser comorbidity measure as variables in the regression.⁷ The derivation of each of these variables from the HES dataset is shown in Appendix Table 1.

Deprivation was measured by the Index of Multiple Deprivation, a methodology used widely within the UK to classify relative deprivation.⁸ To control for clustering, hospital system (known as Trust) was added as a random effect. Robust errors were estimated using the sandwich package.⁹ Modified Poisson regression was chosen in preference to the more common logistic regression because the coefficients can be interpreted as relative risks and not odds ratios. The model was fitted using R, version 4.0.3, geepack library.¹⁰ We carried out three sensitivity analyses, restricting to laboratory-confirmed COVID-19, length of stay ≥3 days, and primary respiratory disease.

For each month, we obtained a standardized mortality ratio (SMR) by fixing the month to the reference month of March 2020 and repredicting the outcome using the existing model. We calculated the ratio of the sum of observed and expected deaths (obtained from the model) in each month, comparing observed deaths to the number we would have expected had those patients been hospitalized in March. We then multiplied each period’s SMR by the March crude mortality to generate monthly adjusted mortality rates. We calculated Poisson confidence intervals around the SMR and used these to obtain confidence intervals for the adjusted rate. The binomial exact method was used to obtain confidence intervals for the crude rate. Multicollinearity was assessed using both the variance inflation factor (VIF) and the condition number test.⁷ All analyses used two-sided statistical tests, and we considered a P value < .05 to be statistically significant without adjustment for multiple testing. The study was exempt from UK National Research Ethics Committee approval because it involved secondary analysis of anonymized data.

The dataset included 115,643 emergency admissions from 179 healthcare systems, of which 103,202 were first admissions eligible for inclusion. A total of 592 patients were excluded due to missing demographic data (0.5%), resulting in 102,610 admissions included in the analysis. Peak hospitalizations occurred in late March to mid April, accounting for 44% of the hospitalizations (Table). Median length of stay for patients who died was 7 days (interquartile range, 3-12). The median age and number of Elixhauser comorbidities decreased in July. The proportion of men decreased between May and July.

The modified Poisson regression had a C statistic of 0.743 (95% CI, 0.740-0.746) (Appendix Table 4). The VIF and condition number test found no evidence of multicollinearity.¹¹

Adjusted mortality decreased each month, from 33.4% in March to 17.4% in July (Figure). The relative risk of death declined progressively to a minimum of 0.52 (95% CI, 0.34-0.80) in July, compared to March.

Admission from another hospital and being female were associated with reduced risk of death. Admission from a skilled nursing facility and being >75 years were associated with increased risk of death. Ten of the 29 Elixhauser comorbidities were associated with increased risk of mortality (cardiac arrhythmia, peripheral vascular disease, other neurologic disorders, renal failure, lymphoma, metastatic cancer, solid tumor without metastasis, coagulopathy, fluid and electrolyte disorders, and anemia). Deprivation and ethnic group were not associated with death among hospitalized patients.

Our study of all emergency hospital admissions in England during the first wave of the COVID-19 pandemic demonstrated that, even after adjusting for patient comorbidity and risk factors, the mortality rate decreased by approximately half over the first 5 months. Although the demographics of hospitalized patients changed over that period (with both the median age and the number of comorbidities decreasing), this does not fully explain the decrease in mortality. It is therefore likely that the decrease is due, at least in part, to an improvement in treatment and/or a reduction in hospital strain.

For example, initially the use of corticosteroids was controversial, in part due to previous experience with severe acute respiratory syndrome and Middle East respiratory syndrome (in which a Cochrane review demonstrated no benefit but potential harm). However, this changed as a result of the Randomized Evaluation of Covid-19 Therapy (RECOVERY) trial,¹² which showed a significant survival benefit.One of the positive defining characteristics of the COVID-19 pandemic has been the intensive collaborative research effort combined with the rapid dissemination and discussion of new management protocols. The RECOVERY trial randomly assigned >11,000 participants in just 3 months, amounting to approximately 15% of all patients hospitalized with COVID-19 in the UK. Its results were widely publicized via professional networks and rapidly adopted into widespread clinical practice.

Examples of other changes include a higher threshold for mechanical ventilation (and a lower threshold for noninvasive ventilation), increased clinician experience, and, potentially, a reduced viral load arising from increased social distancing and mask wearing. Finally, the hospitals and staff themselves were under enormous physical and mental strain in the early months from multiple factors, including unfamiliar working environments, the large-scale redeployment of inexperienced staff, and very high numbers of patients with an unfamiliar disease. These factors all lessened as the initial peak passed. It is therefore likely that the reduction in adjusted mortality we observed arises from a combination of all these factors, as well as other incremental benefits.

The factors associated with increased mortality risk in our study (increasing age, male gender, certain comorbidities, and frailty [with care home residency acting as a proxy in our study]) are consistent with multiple previous reports. Although not the focus of our analysis, we found no effect of ethnicity or deprivation on mortality. This is consistent with many US studies that demonstrate that the widely reported effect of these factors is likely due to differences in exposure to the disease. Once patients are hospitalized, adjusted mortality risks are similar across ethnic groups and deprivation levels.

The strengths of this study include complete capture of hospitalizations across all hospitals and areas in England. Likewise, linking the hospital data to death data from the Office for National Statistics allows complete capture of outcomes, irrespective of where the patient died. This is a significant strength compared to prior studies, which only included in-hospital mortality. Our results are therefore likely robust and a true observation of the mortality trend.

Limitations include the lack of physiologic and laboratory data; having these would have allowed us to adjust for disease severity on admission and strengthened the risk stratification. Likewise, although the complete national coverage is overall a significant strength, aggregating data from numerous areas that might be at different stages of local outbreaks, have different management strategies, and have differing data quality introduces its own biases.

Furthermore, these results predate the second wave in the UK, so we cannot distinguish whether the reduced mortality is due to improved treatment, a seasonal effect, evolution of the virus itself, or a reduction in the strain on hospitals.

This nationwide study indicates that, even after accounting for changing patient characteristics, the mortality of patients hospitalized with COVID-19 in England decreased significantly as the outbreak progressed. This is likely due to a combination of incremental treatment improvements.

The early phase of the coronavirus disease 2019 (COVID-19) pandemic in the United Kingdom (UK) was characterized by uncertainty as clinicians grappled to understand and manage an unfamiliar disease that affected very high numbers of patients amid radically evolving working environments, with little evidence to support their efforts. Early reports indicated high mortality in patients hospitalized with COVID-19.

As the disease became better understood, treatment evolved and the mortality appears to have decreased. For example, two recent papers, a national study of critical care patients in the UK and a single-site study from New York, have demonstrated a significant reduction in adjusted mortality between the pre- and post-peak periods.^1,2 However, the UK study was restricted to patients receiving critical care, potentially introducing bias due to varying critical care admission thresholds over time, while the single-site US study may not be generalizable. Moreover, both studies measured only in-hospital mortality. It remains uncertain therefore whether overall mortality has decreased on a broad scale after accounting for changes in patient characteristics.

The aim of this study was to use a national dataset to assess the casemix-adjusted overall mortality trend in England over the first 5 months of the COVID-19 pandemic.

We conducted a retrospective, secondary analysis of English National Health Services (NHS) hospitals’ admissions of patients at least 18 years of age between March 1 and July 31, 2020. Data were obtained from the Hospital Episode Statistics (HES) admitted patient care dataset.³ This is an administrative dataset that contains data on diagnoses and procedures as well as organizational characteristics and patient demographics for all NHS activity in England. We included all patients with an International Statistical Classification of Diseases, Tenth Revision (ICD-10) diagnosis of U07.1 (COVID-19, virus identified) and U07.2 (COVID-19, virus not identified).

The primary outcome of death within 28 days of admission was obtained by linking to the Civil Registrations (Deaths) - Secondary Care Cut - Information dataset, which includes the date, place, and cause of death from the Office for National Statistics⁴ and which was complete through September 31, 2020. The time horizon of 28 days from admission was chosen to approximate the Public Health England definition of a death from COVID-19 as being within 28 days of testing positive.⁵ We restricted our analysis to emergency admissions of persons age >18 years. If a patient had multiple emergency admissions, we restricted our analysis to the first admission to ensure comparability across hospitalizations and to best represent outcomes from the earliest onset of COVID-19.

We estimated a modified Poisson regression⁶ to predict death at 28 days, with month of admission, region, source of admission, age, deprivation, gender, ethnic group, and the 29 comorbidities in the Elixhauser comorbidity measure as variables in the regression.⁷ The derivation of each of these variables from the HES dataset is shown in Appendix Table 1.

Deprivation was measured by the Index of Multiple Deprivation, a methodology used widely within the UK to classify relative deprivation.⁸ To control for clustering, hospital system (known as Trust) was added as a random effect. Robust errors were estimated using the sandwich package.⁹ Modified Poisson regression was chosen in preference to the more common logistic regression because the coefficients can be interpreted as relative risks and not odds ratios. The model was fitted using R, version 4.0.3, geepack library.¹⁰ We carried out three sensitivity analyses, restricting to laboratory-confirmed COVID-19, length of stay ≥3 days, and primary respiratory disease.

For each month, we obtained a standardized mortality ratio (SMR) by fixing the month to the reference month of March 2020 and repredicting the outcome using the existing model. We calculated the ratio of the sum of observed and expected deaths (obtained from the model) in each month, comparing observed deaths to the number we would have expected had those patients been hospitalized in March. We then multiplied each period’s SMR by the March crude mortality to generate monthly adjusted mortality rates. We calculated Poisson confidence intervals around the SMR and used these to obtain confidence intervals for the adjusted rate. The binomial exact method was used to obtain confidence intervals for the crude rate. Multicollinearity was assessed using both the variance inflation factor (VIF) and the condition number test.⁷ All analyses used two-sided statistical tests, and we considered a P value < .05 to be statistically significant without adjustment for multiple testing. The study was exempt from UK National Research Ethics Committee approval because it involved secondary analysis of anonymized data.

The dataset included 115,643 emergency admissions from 179 healthcare systems, of which 103,202 were first admissions eligible for inclusion. A total of 592 patients were excluded due to missing demographic data (0.5%), resulting in 102,610 admissions included in the analysis. Peak hospitalizations occurred in late March to mid April, accounting for 44% of the hospitalizations (Table). Median length of stay for patients who died was 7 days (interquartile range, 3-12). The median age and number of Elixhauser comorbidities decreased in July. The proportion of men decreased between May and July.

The modified Poisson regression had a C statistic of 0.743 (95% CI, 0.740-0.746) (Appendix Table 4). The VIF and condition number test found no evidence of multicollinearity.¹¹

Adjusted mortality decreased each month, from 33.4% in March to 17.4% in July (Figure). The relative risk of death declined progressively to a minimum of 0.52 (95% CI, 0.34-0.80) in July, compared to March.

Admission from another hospital and being female were associated with reduced risk of death. Admission from a skilled nursing facility and being >75 years were associated with increased risk of death. Ten of the 29 Elixhauser comorbidities were associated with increased risk of mortality (cardiac arrhythmia, peripheral vascular disease, other neurologic disorders, renal failure, lymphoma, metastatic cancer, solid tumor without metastasis, coagulopathy, fluid and electrolyte disorders, and anemia). Deprivation and ethnic group were not associated with death among hospitalized patients.

Our study of all emergency hospital admissions in England during the first wave of the COVID-19 pandemic demonstrated that, even after adjusting for patient comorbidity and risk factors, the mortality rate decreased by approximately half over the first 5 months. Although the demographics of hospitalized patients changed over that period (with both the median age and the number of comorbidities decreasing), this does not fully explain the decrease in mortality. It is therefore likely that the decrease is due, at least in part, to an improvement in treatment and/or a reduction in hospital strain.

For example, initially the use of corticosteroids was controversial, in part due to previous experience with severe acute respiratory syndrome and Middle East respiratory syndrome (in which a Cochrane review demonstrated no benefit but potential harm). However, this changed as a result of the Randomized Evaluation of Covid-19 Therapy (RECOVERY) trial,¹² which showed a significant survival benefit.One of the positive defining characteristics of the COVID-19 pandemic has been the intensive collaborative research effort combined with the rapid dissemination and discussion of new management protocols. The RECOVERY trial randomly assigned >11,000 participants in just 3 months, amounting to approximately 15% of all patients hospitalized with COVID-19 in the UK. Its results were widely publicized via professional networks and rapidly adopted into widespread clinical practice.

Examples of other changes include a higher threshold for mechanical ventilation (and a lower threshold for noninvasive ventilation), increased clinician experience, and, potentially, a reduced viral load arising from increased social distancing and mask wearing. Finally, the hospitals and staff themselves were under enormous physical and mental strain in the early months from multiple factors, including unfamiliar working environments, the large-scale redeployment of inexperienced staff, and very high numbers of patients with an unfamiliar disease. These factors all lessened as the initial peak passed. It is therefore likely that the reduction in adjusted mortality we observed arises from a combination of all these factors, as well as other incremental benefits.

The factors associated with increased mortality risk in our study (increasing age, male gender, certain comorbidities, and frailty [with care home residency acting as a proxy in our study]) are consistent with multiple previous reports. Although not the focus of our analysis, we found no effect of ethnicity or deprivation on mortality. This is consistent with many US studies that demonstrate that the widely reported effect of these factors is likely due to differences in exposure to the disease. Once patients are hospitalized, adjusted mortality risks are similar across ethnic groups and deprivation levels.

The strengths of this study include complete capture of hospitalizations across all hospitals and areas in England. Likewise, linking the hospital data to death data from the Office for National Statistics allows complete capture of outcomes, irrespective of where the patient died. This is a significant strength compared to prior studies, which only included in-hospital mortality. Our results are therefore likely robust and a true observation of the mortality trend.

Limitations include the lack of physiologic and laboratory data; having these would have allowed us to adjust for disease severity on admission and strengthened the risk stratification. Likewise, although the complete national coverage is overall a significant strength, aggregating data from numerous areas that might be at different stages of local outbreaks, have different management strategies, and have differing data quality introduces its own biases.

Furthermore, these results predate the second wave in the UK, so we cannot distinguish whether the reduced mortality is due to improved treatment, a seasonal effect, evolution of the virus itself, or a reduction in the strain on hospitals.

This nationwide study indicates that, even after accounting for changing patient characteristics, the mortality of patients hospitalized with COVID-19 in England decreased significantly as the outbreak progressed. This is likely due to a combination of incremental treatment improvements.

The early phase of the coronavirus disease 2019 (COVID-19) pandemic in the United Kingdom (UK) was characterized by uncertainty as clinicians grappled to understand and manage an unfamiliar disease that affected very high numbers of patients amid radically evolving working environments, with little evidence to support their efforts. Early reports indicated high mortality in patients hospitalized with COVID-19.

As the disease became better understood, treatment evolved and the mortality appears to have decreased. For example, two recent papers, a national study of critical care patients in the UK and a single-site study from New York, have demonstrated a significant reduction in adjusted mortality between the pre- and post-peak periods.^1,2 However, the UK study was restricted to patients receiving critical care, potentially introducing bias due to varying critical care admission thresholds over time, while the single-site US study may not be generalizable. Moreover, both studies measured only in-hospital mortality. It remains uncertain therefore whether overall mortality has decreased on a broad scale after accounting for changes in patient characteristics.

The aim of this study was to use a national dataset to assess the casemix-adjusted overall mortality trend in England over the first 5 months of the COVID-19 pandemic.

We conducted a retrospective, secondary analysis of English National Health Services (NHS) hospitals’ admissions of patients at least 18 years of age between March 1 and July 31, 2020. Data were obtained from the Hospital Episode Statistics (HES) admitted patient care dataset.³ This is an administrative dataset that contains data on diagnoses and procedures as well as organizational characteristics and patient demographics for all NHS activity in England. We included all patients with an International Statistical Classification of Diseases, Tenth Revision (ICD-10) diagnosis of U07.1 (COVID-19, virus identified) and U07.2 (COVID-19, virus not identified).

The primary outcome of death within 28 days of admission was obtained by linking to the Civil Registrations (Deaths) - Secondary Care Cut - Information dataset, which includes the date, place, and cause of death from the Office for National Statistics⁴ and which was complete through September 31, 2020. The time horizon of 28 days from admission was chosen to approximate the Public Health England definition of a death from COVID-19 as being within 28 days of testing positive.⁵ We restricted our analysis to emergency admissions of persons age >18 years. If a patient had multiple emergency admissions, we restricted our analysis to the first admission to ensure comparability across hospitalizations and to best represent outcomes from the earliest onset of COVID-19.

We estimated a modified Poisson regression⁶ to predict death at 28 days, with month of admission, region, source of admission, age, deprivation, gender, ethnic group, and the 29 comorbidities in the Elixhauser comorbidity measure as variables in the regression.⁷ The derivation of each of these variables from the HES dataset is shown in Appendix Table 1.

Deprivation was measured by the Index of Multiple Deprivation, a methodology used widely within the UK to classify relative deprivation.⁸ To control for clustering, hospital system (known as Trust) was added as a random effect. Robust errors were estimated using the sandwich package.⁹ Modified Poisson regression was chosen in preference to the more common logistic regression because the coefficients can be interpreted as relative risks and not odds ratios. The model was fitted using R, version 4.0.3, geepack library.¹⁰ We carried out three sensitivity analyses, restricting to laboratory-confirmed COVID-19, length of stay ≥3 days, and primary respiratory disease.

For each month, we obtained a standardized mortality ratio (SMR) by fixing the month to the reference month of March 2020 and repredicting the outcome using the existing model. We calculated the ratio of the sum of observed and expected deaths (obtained from the model) in each month, comparing observed deaths to the number we would have expected had those patients been hospitalized in March. We then multiplied each period’s SMR by the March crude mortality to generate monthly adjusted mortality rates. We calculated Poisson confidence intervals around the SMR and used these to obtain confidence intervals for the adjusted rate. The binomial exact method was used to obtain confidence intervals for the crude rate. Multicollinearity was assessed using both the variance inflation factor (VIF) and the condition number test.⁷ All analyses used two-sided statistical tests, and we considered a P value < .05 to be statistically significant without adjustment for multiple testing. The study was exempt from UK National Research Ethics Committee approval because it involved secondary analysis of anonymized data.

The dataset included 115,643 emergency admissions from 179 healthcare systems, of which 103,202 were first admissions eligible for inclusion. A total of 592 patients were excluded due to missing demographic data (0.5%), resulting in 102,610 admissions included in the analysis. Peak hospitalizations occurred in late March to mid April, accounting for 44% of the hospitalizations (Table). Median length of stay for patients who died was 7 days (interquartile range, 3-12). The median age and number of Elixhauser comorbidities decreased in July. The proportion of men decreased between May and July.

The modified Poisson regression had a C statistic of 0.743 (95% CI, 0.740-0.746) (Appendix Table 4). The VIF and condition number test found no evidence of multicollinearity.¹¹

Adjusted mortality decreased each month, from 33.4% in March to 17.4% in July (Figure). The relative risk of death declined progressively to a minimum of 0.52 (95% CI, 0.34-0.80) in July, compared to March.

Admission from another hospital and being female were associated with reduced risk of death. Admission from a skilled nursing facility and being >75 years were associated with increased risk of death. Ten of the 29 Elixhauser comorbidities were associated with increased risk of mortality (cardiac arrhythmia, peripheral vascular disease, other neurologic disorders, renal failure, lymphoma, metastatic cancer, solid tumor without metastasis, coagulopathy, fluid and electrolyte disorders, and anemia). Deprivation and ethnic group were not associated with death among hospitalized patients.

Our study of all emergency hospital admissions in England during the first wave of the COVID-19 pandemic demonstrated that, even after adjusting for patient comorbidity and risk factors, the mortality rate decreased by approximately half over the first 5 months. Although the demographics of hospitalized patients changed over that period (with both the median age and the number of comorbidities decreasing), this does not fully explain the decrease in mortality. It is therefore likely that the decrease is due, at least in part, to an improvement in treatment and/or a reduction in hospital strain.

For example, initially the use of corticosteroids was controversial, in part due to previous experience with severe acute respiratory syndrome and Middle East respiratory syndrome (in which a Cochrane review demonstrated no benefit but potential harm). However, this changed as a result of the Randomized Evaluation of Covid-19 Therapy (RECOVERY) trial,¹² which showed a significant survival benefit.One of the positive defining characteristics of the COVID-19 pandemic has been the intensive collaborative research effort combined with the rapid dissemination and discussion of new management protocols. The RECOVERY trial randomly assigned >11,000 participants in just 3 months, amounting to approximately 15% of all patients hospitalized with COVID-19 in the UK. Its results were widely publicized via professional networks and rapidly adopted into widespread clinical practice.

Examples of other changes include a higher threshold for mechanical ventilation (and a lower threshold for noninvasive ventilation), increased clinician experience, and, potentially, a reduced viral load arising from increased social distancing and mask wearing. Finally, the hospitals and staff themselves were under enormous physical and mental strain in the early months from multiple factors, including unfamiliar working environments, the large-scale redeployment of inexperienced staff, and very high numbers of patients with an unfamiliar disease. These factors all lessened as the initial peak passed. It is therefore likely that the reduction in adjusted mortality we observed arises from a combination of all these factors, as well as other incremental benefits.

The factors associated with increased mortality risk in our study (increasing age, male gender, certain comorbidities, and frailty [with care home residency acting as a proxy in our study]) are consistent with multiple previous reports. Although not the focus of our analysis, we found no effect of ethnicity or deprivation on mortality. This is consistent with many US studies that demonstrate that the widely reported effect of these factors is likely due to differences in exposure to the disease. Once patients are hospitalized, adjusted mortality risks are similar across ethnic groups and deprivation levels.

The strengths of this study include complete capture of hospitalizations across all hospitals and areas in England. Likewise, linking the hospital data to death data from the Office for National Statistics allows complete capture of outcomes, irrespective of where the patient died. This is a significant strength compared to prior studies, which only included in-hospital mortality. Our results are therefore likely robust and a true observation of the mortality trend.

Limitations include the lack of physiologic and laboratory data; having these would have allowed us to adjust for disease severity on admission and strengthened the risk stratification. Likewise, although the complete national coverage is overall a significant strength, aggregating data from numerous areas that might be at different stages of local outbreaks, have different management strategies, and have differing data quality introduces its own biases.

Furthermore, these results predate the second wave in the UK, so we cannot distinguish whether the reduced mortality is due to improved treatment, a seasonal effect, evolution of the virus itself, or a reduction in the strain on hospitals.

This nationwide study indicates that, even after accounting for changing patient characteristics, the mortality of patients hospitalized with COVID-19 in England decreased significantly as the outbreak progressed. This is likely due to a combination of incremental treatment improvements.

Higher fiber intake may be associated with decreased risk of depression in premenopausal women, new research suggests.

Nic_Ol/Thinkstock

Investigators analyzed data from close to 6,000 pre- and postmenopausal women. They found that, in premenopausal women, dietary fiber intake was higher among those without depression versus their counterparts with the disorder in a dose-dependent manner. However, there appeared to be no relationship between higher fiber intake and depression risk in postmenopausal women.

“We think the most important finding of our study is that dietary fiber intake was inversely associated with depression in premenopausal but not postmenopausal women,” lead author Yunsun Kim, MD, resident, department of family medicine, Chung-Ang University Hospital, Seoul, South Korea, said in an interview.

“We hope that the findings of this study could form the basis of future investigations to determine the causal relationship between dietary fiber intake and depression,” she added.

The study was published online Dec. 21, 2020, in Menopause.
 

Gut-brain interaction

The prevalence of depression is twice as high in women, compared with men, which may be attributable to a number of factors, including hormonal status – especially during menstruation and menopause, the authors wrote.

Previous research suggests a potential association between dietary fiber and depression in premenopausal women and between estrogen and gut microbiota. Fiber intake has an impact on gut microbiota, Dr. Kim said.

“We are motivated by the fact that depression provokes disease burden internationally and we would like to find modifiable factors that could prevent depression, especially in women, who are more vulnerable to depression,” she noted.

To investigate, the researchers drew on data from the Korea National Health and Nutrition Examination Survey for 2014, 2016, and 2018. Of the total number of women who met inclusion criteria (n = 5807; mean age, 47.11), roughly half were premenopausal and half were postmenopausal (n = 2,949 [mean age, 36.23 years] and n = 2,868 [mean age, 62.73], respectively).

Dietary fiber intake was assessed using the 24-hour dietary recall method, while depression was assessed using the Patient Health Questionnaire-9. The researchers used the Dietary Reference Intakes for Koreans to define a sufficient intake of dietary fiber (i.e., 12 g/1,000 kcal).

Covariates included chronic diseases, body mass index, medications, smoking status, alcohol use, physical activity, and sociodemographic factors.

When the researchers looked at all participants, they found that the estimated mean dietary fiber intake was significantly higher in women without depression, compared with those with depression (14.07 g/1,000 kcal/d; 95% confidence interval, 13.85-14.29 vs. 12.67 g/1,000 kcal/d; 95% CI, 11.79-13.55; P = .003).

Although the relationship remained significant in premenopausal women, it lost significance in postmenopausal women.

A 5% decrease in the prevalence of depression in premenopausal (but not postmenopausal) women was found in those with an increased intake of dietary fiber – i..e, there was a 1-g increase for every 1,000 kcal of daily energy intake, after adjusting for potential confounders in premenopausal women (OR, 0.949; 95% CI, 0.906-0.993]).

“The inverse relationship between dietary fiber intake and depression could be explained by the gut-brain interactions,” said Dr. Kim.

“Changes in the gut microbiota composition may affect neurotransmission and various neuropsychiatric phenomena in the brain,” she said, noting that previous studies have suggested that dietary fiber intake “may modulate the richness and diversity of the gut microbiota, and this change may promote brain health by affecting neurotransmission.”

Because postmenopausal women experience estrogen depletion, “the decreased interaction between estrogen and the gut microbiota may be related to the insignificant association between dietary fiber intake and depression in postmenopausal women,” she said.

Despite the lack of a significant association between postmenopausal depression and fiber intake, Dr. Kim said she “advises middle-aged women to have dietary fiber–rich diets, regardless of their menopausal status.”
 

Link between food and mood

In a comment, Stephanie S. Faubion, MD, MBA, a professor and chair of the department of medicine and the Penny and Bill George director of the Mayo Clinic’s Center for Women’s Health in Rochester, Minn., noted the study was cross-sectional and therefore the direction of the association could not be determined and “causality cannot be assumed.”

It is possible that “depressed women are less likely to eat fiber than women without depression. For example, a depressed woman may be more likely to sit on the couch eating Cheetos than shopping for and preparing a healthy meal,” said Dr. Faubion, who is also the medical director of the North American Menopause Society and was not involved with the study.

She noted that other potential confounders, including access to fresh fruits and vegetables or geographic locations could also “impact the findings and it is important that we do not somehow imply that eating a high-fiber diet can in any way treat a major depression.”

Nevertheless, the study does “add to the body of evidence suggesting a link between diet and overall health, including brain health,” Dr. Faubion said.

One take-home message for practicing clinicians is that a healthy diet that includes fiber may benefit women (and men) for a number of reasons and “appears to be linked to mood.”

More research is needed “to determine the pathophysiologic mechanisms (such as potential brain-gut connection that involves the microbiome) that may explain this association,” Dr. Faubion added.

No source of funding listed. Dr. Kim and coauthors, as well as Dr. Faubion, disclosed no relevant financial relationships.

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

Higher fiber intake may be associated with decreased risk of depression in premenopausal women, new research suggests.

Nic_Ol/Thinkstock

Investigators analyzed data from close to 6,000 pre- and postmenopausal women. They found that, in premenopausal women, dietary fiber intake was higher among those without depression versus their counterparts with the disorder in a dose-dependent manner. However, there appeared to be no relationship between higher fiber intake and depression risk in postmenopausal women.

“We think the most important finding of our study is that dietary fiber intake was inversely associated with depression in premenopausal but not postmenopausal women,” lead author Yunsun Kim, MD, resident, department of family medicine, Chung-Ang University Hospital, Seoul, South Korea, said in an interview.

“We hope that the findings of this study could form the basis of future investigations to determine the causal relationship between dietary fiber intake and depression,” she added.

The study was published online Dec. 21, 2020, in Menopause.
 

Gut-brain interaction

The prevalence of depression is twice as high in women, compared with men, which may be attributable to a number of factors, including hormonal status – especially during menstruation and menopause, the authors wrote.

Previous research suggests a potential association between dietary fiber and depression in premenopausal women and between estrogen and gut microbiota. Fiber intake has an impact on gut microbiota, Dr. Kim said.

“We are motivated by the fact that depression provokes disease burden internationally and we would like to find modifiable factors that could prevent depression, especially in women, who are more vulnerable to depression,” she noted.

To investigate, the researchers drew on data from the Korea National Health and Nutrition Examination Survey for 2014, 2016, and 2018. Of the total number of women who met inclusion criteria (n = 5807; mean age, 47.11), roughly half were premenopausal and half were postmenopausal (n = 2,949 [mean age, 36.23 years] and n = 2,868 [mean age, 62.73], respectively).

Dietary fiber intake was assessed using the 24-hour dietary recall method, while depression was assessed using the Patient Health Questionnaire-9. The researchers used the Dietary Reference Intakes for Koreans to define a sufficient intake of dietary fiber (i.e., 12 g/1,000 kcal).

Covariates included chronic diseases, body mass index, medications, smoking status, alcohol use, physical activity, and sociodemographic factors.

When the researchers looked at all participants, they found that the estimated mean dietary fiber intake was significantly higher in women without depression, compared with those with depression (14.07 g/1,000 kcal/d; 95% confidence interval, 13.85-14.29 vs. 12.67 g/1,000 kcal/d; 95% CI, 11.79-13.55; P = .003).

Although the relationship remained significant in premenopausal women, it lost significance in postmenopausal women.

A 5% decrease in the prevalence of depression in premenopausal (but not postmenopausal) women was found in those with an increased intake of dietary fiber – i..e, there was a 1-g increase for every 1,000 kcal of daily energy intake, after adjusting for potential confounders in premenopausal women (OR, 0.949; 95% CI, 0.906-0.993]).

“The inverse relationship between dietary fiber intake and depression could be explained by the gut-brain interactions,” said Dr. Kim.

“Changes in the gut microbiota composition may affect neurotransmission and various neuropsychiatric phenomena in the brain,” she said, noting that previous studies have suggested that dietary fiber intake “may modulate the richness and diversity of the gut microbiota, and this change may promote brain health by affecting neurotransmission.”

Because postmenopausal women experience estrogen depletion, “the decreased interaction between estrogen and the gut microbiota may be related to the insignificant association between dietary fiber intake and depression in postmenopausal women,” she said.

Despite the lack of a significant association between postmenopausal depression and fiber intake, Dr. Kim said she “advises middle-aged women to have dietary fiber–rich diets, regardless of their menopausal status.”
 

Link between food and mood

In a comment, Stephanie S. Faubion, MD, MBA, a professor and chair of the department of medicine and the Penny and Bill George director of the Mayo Clinic’s Center for Women’s Health in Rochester, Minn., noted the study was cross-sectional and therefore the direction of the association could not be determined and “causality cannot be assumed.”

It is possible that “depressed women are less likely to eat fiber than women without depression. For example, a depressed woman may be more likely to sit on the couch eating Cheetos than shopping for and preparing a healthy meal,” said Dr. Faubion, who is also the medical director of the North American Menopause Society and was not involved with the study.

She noted that other potential confounders, including access to fresh fruits and vegetables or geographic locations could also “impact the findings and it is important that we do not somehow imply that eating a high-fiber diet can in any way treat a major depression.”

Nevertheless, the study does “add to the body of evidence suggesting a link between diet and overall health, including brain health,” Dr. Faubion said.

One take-home message for practicing clinicians is that a healthy diet that includes fiber may benefit women (and men) for a number of reasons and “appears to be linked to mood.”

More research is needed “to determine the pathophysiologic mechanisms (such as potential brain-gut connection that involves the microbiome) that may explain this association,” Dr. Faubion added.

No source of funding listed. Dr. Kim and coauthors, as well as Dr. Faubion, disclosed no relevant financial relationships.

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

Higher fiber intake may be associated with decreased risk of depression in premenopausal women, new research suggests.

Nic_Ol/Thinkstock

Investigators analyzed data from close to 6,000 pre- and postmenopausal women. They found that, in premenopausal women, dietary fiber intake was higher among those without depression versus their counterparts with the disorder in a dose-dependent manner. However, there appeared to be no relationship between higher fiber intake and depression risk in postmenopausal women.

“We think the most important finding of our study is that dietary fiber intake was inversely associated with depression in premenopausal but not postmenopausal women,” lead author Yunsun Kim, MD, resident, department of family medicine, Chung-Ang University Hospital, Seoul, South Korea, said in an interview.

“We hope that the findings of this study could form the basis of future investigations to determine the causal relationship between dietary fiber intake and depression,” she added.

The study was published online Dec. 21, 2020, in Menopause.
 

Gut-brain interaction

The prevalence of depression is twice as high in women, compared with men, which may be attributable to a number of factors, including hormonal status – especially during menstruation and menopause, the authors wrote.

Previous research suggests a potential association between dietary fiber and depression in premenopausal women and between estrogen and gut microbiota. Fiber intake has an impact on gut microbiota, Dr. Kim said.

“We are motivated by the fact that depression provokes disease burden internationally and we would like to find modifiable factors that could prevent depression, especially in women, who are more vulnerable to depression,” she noted.

To investigate, the researchers drew on data from the Korea National Health and Nutrition Examination Survey for 2014, 2016, and 2018. Of the total number of women who met inclusion criteria (n = 5807; mean age, 47.11), roughly half were premenopausal and half were postmenopausal (n = 2,949 [mean age, 36.23 years] and n = 2,868 [mean age, 62.73], respectively).

Dietary fiber intake was assessed using the 24-hour dietary recall method, while depression was assessed using the Patient Health Questionnaire-9. The researchers used the Dietary Reference Intakes for Koreans to define a sufficient intake of dietary fiber (i.e., 12 g/1,000 kcal).

Covariates included chronic diseases, body mass index, medications, smoking status, alcohol use, physical activity, and sociodemographic factors.

When the researchers looked at all participants, they found that the estimated mean dietary fiber intake was significantly higher in women without depression, compared with those with depression (14.07 g/1,000 kcal/d; 95% confidence interval, 13.85-14.29 vs. 12.67 g/1,000 kcal/d; 95% CI, 11.79-13.55; P = .003).

Although the relationship remained significant in premenopausal women, it lost significance in postmenopausal women.

A 5% decrease in the prevalence of depression in premenopausal (but not postmenopausal) women was found in those with an increased intake of dietary fiber – i..e, there was a 1-g increase for every 1,000 kcal of daily energy intake, after adjusting for potential confounders in premenopausal women (OR, 0.949; 95% CI, 0.906-0.993]).

“The inverse relationship between dietary fiber intake and depression could be explained by the gut-brain interactions,” said Dr. Kim.

“Changes in the gut microbiota composition may affect neurotransmission and various neuropsychiatric phenomena in the brain,” she said, noting that previous studies have suggested that dietary fiber intake “may modulate the richness and diversity of the gut microbiota, and this change may promote brain health by affecting neurotransmission.”

Because postmenopausal women experience estrogen depletion, “the decreased interaction between estrogen and the gut microbiota may be related to the insignificant association between dietary fiber intake and depression in postmenopausal women,” she said.

Despite the lack of a significant association between postmenopausal depression and fiber intake, Dr. Kim said she “advises middle-aged women to have dietary fiber–rich diets, regardless of their menopausal status.”
 

Link between food and mood

In a comment, Stephanie S. Faubion, MD, MBA, a professor and chair of the department of medicine and the Penny and Bill George director of the Mayo Clinic’s Center for Women’s Health in Rochester, Minn., noted the study was cross-sectional and therefore the direction of the association could not be determined and “causality cannot be assumed.”

It is possible that “depressed women are less likely to eat fiber than women without depression. For example, a depressed woman may be more likely to sit on the couch eating Cheetos than shopping for and preparing a healthy meal,” said Dr. Faubion, who is also the medical director of the North American Menopause Society and was not involved with the study.

She noted that other potential confounders, including access to fresh fruits and vegetables or geographic locations could also “impact the findings and it is important that we do not somehow imply that eating a high-fiber diet can in any way treat a major depression.”

Nevertheless, the study does “add to the body of evidence suggesting a link between diet and overall health, including brain health,” Dr. Faubion said.

One take-home message for practicing clinicians is that a healthy diet that includes fiber may benefit women (and men) for a number of reasons and “appears to be linked to mood.”

More research is needed “to determine the pathophysiologic mechanisms (such as potential brain-gut connection that involves the microbiome) that may explain this association,” Dr. Faubion added.

No source of funding listed. Dr. Kim and coauthors, as well as Dr. Faubion, disclosed no relevant financial relationships.

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

How should I be approaching cervical cancer screening: with primary human papillomavirus (HPV) testing, or cotesting? We get this question all the time from clinicians. Although they have heard of the latest cervical cancer screening guidelines for stand-alone “primary” HPV testing, they are still ordering cervical cytology (Papanicolaou, or Pap, test) for women aged 21 to 29 years and cotesting (cervical cytology with HPV testing) for women with a cervix aged 30 and older.

Changes in cervical cancer testing guidance

Cervical cancer occurs in more than 13,000 women in the United States annually.¹ High-risk types of HPV—the known cause of cervical cancer—also cause a large majority of cancers of the anus, vagina, vulva, and oropharynx.²

Cervical cancer screening programs in the United States have markedly decreased the incidence of and mortality from cervical cancer since introduction of the Pap smear in the 1950s. In 2000, HPV testing was approved by the US Food and Drug Administration (FDA) as a reflex test to a Pap smear result of atypical squamous cells of undetermined significance (ASC-US). HPV testing was then approved for use with cytology as a cotest in 2003 and subsequently as a primary stand-alone test in 2014.

Recently, the American Cancer Society (ACS) released new cervical screening guidelines that depart from prior guidelines.³ They recommend not to screen 21- to 24-year-olds and to start screening at age 25 until age 65 with the preferred strategy of primary HPV testing every 5 years, using an FDA-approved HPV test. Alternative screening strategies are cytology (Pap) every 3 years or cotesting every 5 years.

The 2018 US Preventive Services Task Force (USPSTF) guidelines differ from the ACS guidelines. The USPSTF recommends cytology every 3 years as the preferred method for women with a cervix who are aged 21 to 29 years and, for women with a cervix who are aged 30 to 65 years, the option for cytology every 3 years, primary HPV testing every 5 years, or cotesting every 5 years (TABLE).⁴

Why the reluctance to switch to HPV testing?

Despite FDA approval in 2014 for primary HPV testing and concurrent professional society guidance to use this testing strategy in women with a cervix who are aged 25 years and older, few practices in the United States have switched over to primary HPV testing for cervical cancer screening.^5,6 Several reasons underlie this inertia:

• Many practices currently use HPV tests that are not FDA approved for primary HPV testing.
• Until recently, national screening guidelines did not recommend primary HPV testing as the preferred testing strategy.
• Long-established guidance on the importance of regular cervical cytology screening promoted by the ACS and others (which especially impacts women with a cervix older than age 50 who guide their younger daughters) will rely on significant re-education to move away from the established “Pap smear” cultural icon to a new approach.
• Last but not least, companies that manufacture HPV tests and laboratories integrated to offer such tests not yet approved for primary screening are promoting reliance on the prior proven cotest strategy. They have lobbied to preserve cotesting as a primary test, with some laboratory database studies showing gaps in detection with HPV test screening alone.^7-9

Currently, the FDA-approved HPV tests for primary HPV screening include the Cobas HPV test (Roche) and the BD Onclarity HPV assay (Becton, Dickinson and Company). Both are DNA tests for 14 high-risk types of HPV that include genotyping for HPV 16 and 18.

Continue to: Follow the evidence...

Several trials in Europe and Canada provide supporting evidence for primary HPV testing, and many European countries have moved to primary HPV testing as their preferred screening method.^10,11 The new ACS guidelines put us more in sync with the rest of the world, where HPV testing is the dominant strategy.

It is true that doing additional tests will find more disease; cotesting has been shown to very minimally increase detection of cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) compared with HPV testing alone, but it incurs many more costs and procedures.¹² The vast majority of cervical cancer is HPV positive, and cytology still can be used as a triage to primary HPV screening until tests with better sensitivity and/or specificity (such as dual stain and methylation) can be employed to reduce unnecessary “false-positive” driven procedures.

As mentioned, many strong forces are trying to keep cotesting as the preferred strategy. It is important for clinicians to recognize the corporate investment into screening platforms, relationships, and products that underlie some of these efforts so as not to be unfairly influenced by their lobbying. Data from well-conducted, high-quality studies should be the evidence on which one bases a cervical cancer screening strategy.

Innovation catalyzes change

We acknowledge that it is difficult to give up something you have been doing for decades, so there is natural resistance by both patients and clinicians to move the Pap smear into a secondary role. But the data support primary HPV testing as the best screening option from a public health perspective.

At some point, hopefully soon, primary HPV testing will receive approval for self-sampling; this has the potential to reach patients in rural or remote locations who may otherwise not get screened for cervical cancer.¹³

The 2019 risk-based management guidelines from the ASCCP (American Society for Colposcopy and Cervical Pathology) also incorporate the use of HPV-based screening and surveillance after abnormal tests or colposcopy. Therefore, switching to primary HPV screening will not impact your ability to follow patients appropriately based on clinical guidelines.

Our advice to clinicians is to switch to primary HPV screening now if possible. If that is not feasible, continue your current strategy until you can make the change. And, of course, we recommend that you implement an HPV vaccination program in your practice to maximize primary prevention of HPV-related cancers. ●

How should I be approaching cervical cancer screening: with primary human papillomavirus (HPV) testing, or cotesting? We get this question all the time from clinicians. Although they have heard of the latest cervical cancer screening guidelines for stand-alone “primary” HPV testing, they are still ordering cervical cytology (Papanicolaou, or Pap, test) for women aged 21 to 29 years and cotesting (cervical cytology with HPV testing) for women with a cervix aged 30 and older.

Changes in cervical cancer testing guidance

Cervical cancer occurs in more than 13,000 women in the United States annually.¹ High-risk types of HPV—the known cause of cervical cancer—also cause a large majority of cancers of the anus, vagina, vulva, and oropharynx.²

Cervical cancer screening programs in the United States have markedly decreased the incidence of and mortality from cervical cancer since introduction of the Pap smear in the 1950s. In 2000, HPV testing was approved by the US Food and Drug Administration (FDA) as a reflex test to a Pap smear result of atypical squamous cells of undetermined significance (ASC-US). HPV testing was then approved for use with cytology as a cotest in 2003 and subsequently as a primary stand-alone test in 2014.

Recently, the American Cancer Society (ACS) released new cervical screening guidelines that depart from prior guidelines.³ They recommend not to screen 21- to 24-year-olds and to start screening at age 25 until age 65 with the preferred strategy of primary HPV testing every 5 years, using an FDA-approved HPV test. Alternative screening strategies are cytology (Pap) every 3 years or cotesting every 5 years.

The 2018 US Preventive Services Task Force (USPSTF) guidelines differ from the ACS guidelines. The USPSTF recommends cytology every 3 years as the preferred method for women with a cervix who are aged 21 to 29 years and, for women with a cervix who are aged 30 to 65 years, the option for cytology every 3 years, primary HPV testing every 5 years, or cotesting every 5 years (TABLE).⁴

Why the reluctance to switch to HPV testing?

Despite FDA approval in 2014 for primary HPV testing and concurrent professional society guidance to use this testing strategy in women with a cervix who are aged 25 years and older, few practices in the United States have switched over to primary HPV testing for cervical cancer screening.^5,6 Several reasons underlie this inertia:

• Many practices currently use HPV tests that are not FDA approved for primary HPV testing.
• Until recently, national screening guidelines did not recommend primary HPV testing as the preferred testing strategy.
• Long-established guidance on the importance of regular cervical cytology screening promoted by the ACS and others (which especially impacts women with a cervix older than age 50 who guide their younger daughters) will rely on significant re-education to move away from the established “Pap smear” cultural icon to a new approach.
• Last but not least, companies that manufacture HPV tests and laboratories integrated to offer such tests not yet approved for primary screening are promoting reliance on the prior proven cotest strategy. They have lobbied to preserve cotesting as a primary test, with some laboratory database studies showing gaps in detection with HPV test screening alone.^7-9

Currently, the FDA-approved HPV tests for primary HPV screening include the Cobas HPV test (Roche) and the BD Onclarity HPV assay (Becton, Dickinson and Company). Both are DNA tests for 14 high-risk types of HPV that include genotyping for HPV 16 and 18.

Continue to: Follow the evidence...

Several trials in Europe and Canada provide supporting evidence for primary HPV testing, and many European countries have moved to primary HPV testing as their preferred screening method.^10,11 The new ACS guidelines put us more in sync with the rest of the world, where HPV testing is the dominant strategy.

It is true that doing additional tests will find more disease; cotesting has been shown to very minimally increase detection of cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) compared with HPV testing alone, but it incurs many more costs and procedures.¹² The vast majority of cervical cancer is HPV positive, and cytology still can be used as a triage to primary HPV screening until tests with better sensitivity and/or specificity (such as dual stain and methylation) can be employed to reduce unnecessary “false-positive” driven procedures.

As mentioned, many strong forces are trying to keep cotesting as the preferred strategy. It is important for clinicians to recognize the corporate investment into screening platforms, relationships, and products that underlie some of these efforts so as not to be unfairly influenced by their lobbying. Data from well-conducted, high-quality studies should be the evidence on which one bases a cervical cancer screening strategy.

Innovation catalyzes change

We acknowledge that it is difficult to give up something you have been doing for decades, so there is natural resistance by both patients and clinicians to move the Pap smear into a secondary role. But the data support primary HPV testing as the best screening option from a public health perspective.

At some point, hopefully soon, primary HPV testing will receive approval for self-sampling; this has the potential to reach patients in rural or remote locations who may otherwise not get screened for cervical cancer.¹³

The 2019 risk-based management guidelines from the ASCCP (American Society for Colposcopy and Cervical Pathology) also incorporate the use of HPV-based screening and surveillance after abnormal tests or colposcopy. Therefore, switching to primary HPV screening will not impact your ability to follow patients appropriately based on clinical guidelines.

Our advice to clinicians is to switch to primary HPV screening now if possible. If that is not feasible, continue your current strategy until you can make the change. And, of course, we recommend that you implement an HPV vaccination program in your practice to maximize primary prevention of HPV-related cancers. ●

How should I be approaching cervical cancer screening: with primary human papillomavirus (HPV) testing, or cotesting? We get this question all the time from clinicians. Although they have heard of the latest cervical cancer screening guidelines for stand-alone “primary” HPV testing, they are still ordering cervical cytology (Papanicolaou, or Pap, test) for women aged 21 to 29 years and cotesting (cervical cytology with HPV testing) for women with a cervix aged 30 and older.

Changes in cervical cancer testing guidance

Cervical cancer occurs in more than 13,000 women in the United States annually.¹ High-risk types of HPV—the known cause of cervical cancer—also cause a large majority of cancers of the anus, vagina, vulva, and oropharynx.²

Cervical cancer screening programs in the United States have markedly decreased the incidence of and mortality from cervical cancer since introduction of the Pap smear in the 1950s. In 2000, HPV testing was approved by the US Food and Drug Administration (FDA) as a reflex test to a Pap smear result of atypical squamous cells of undetermined significance (ASC-US). HPV testing was then approved for use with cytology as a cotest in 2003 and subsequently as a primary stand-alone test in 2014.

Recently, the American Cancer Society (ACS) released new cervical screening guidelines that depart from prior guidelines.³ They recommend not to screen 21- to 24-year-olds and to start screening at age 25 until age 65 with the preferred strategy of primary HPV testing every 5 years, using an FDA-approved HPV test. Alternative screening strategies are cytology (Pap) every 3 years or cotesting every 5 years.

The 2018 US Preventive Services Task Force (USPSTF) guidelines differ from the ACS guidelines. The USPSTF recommends cytology every 3 years as the preferred method for women with a cervix who are aged 21 to 29 years and, for women with a cervix who are aged 30 to 65 years, the option for cytology every 3 years, primary HPV testing every 5 years, or cotesting every 5 years (TABLE).⁴

Why the reluctance to switch to HPV testing?

Despite FDA approval in 2014 for primary HPV testing and concurrent professional society guidance to use this testing strategy in women with a cervix who are aged 25 years and older, few practices in the United States have switched over to primary HPV testing for cervical cancer screening.^5,6 Several reasons underlie this inertia:

• Many practices currently use HPV tests that are not FDA approved for primary HPV testing.
• Until recently, national screening guidelines did not recommend primary HPV testing as the preferred testing strategy.
• Long-established guidance on the importance of regular cervical cytology screening promoted by the ACS and others (which especially impacts women with a cervix older than age 50 who guide their younger daughters) will rely on significant re-education to move away from the established “Pap smear” cultural icon to a new approach.
• Last but not least, companies that manufacture HPV tests and laboratories integrated to offer such tests not yet approved for primary screening are promoting reliance on the prior proven cotest strategy. They have lobbied to preserve cotesting as a primary test, with some laboratory database studies showing gaps in detection with HPV test screening alone.^7-9

Currently, the FDA-approved HPV tests for primary HPV screening include the Cobas HPV test (Roche) and the BD Onclarity HPV assay (Becton, Dickinson and Company). Both are DNA tests for 14 high-risk types of HPV that include genotyping for HPV 16 and 18.

Continue to: Follow the evidence...

Several trials in Europe and Canada provide supporting evidence for primary HPV testing, and many European countries have moved to primary HPV testing as their preferred screening method.^10,11 The new ACS guidelines put us more in sync with the rest of the world, where HPV testing is the dominant strategy.

It is true that doing additional tests will find more disease; cotesting has been shown to very minimally increase detection of cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) compared with HPV testing alone, but it incurs many more costs and procedures.¹² The vast majority of cervical cancer is HPV positive, and cytology still can be used as a triage to primary HPV screening until tests with better sensitivity and/or specificity (such as dual stain and methylation) can be employed to reduce unnecessary “false-positive” driven procedures.

As mentioned, many strong forces are trying to keep cotesting as the preferred strategy. It is important for clinicians to recognize the corporate investment into screening platforms, relationships, and products that underlie some of these efforts so as not to be unfairly influenced by their lobbying. Data from well-conducted, high-quality studies should be the evidence on which one bases a cervical cancer screening strategy.

Innovation catalyzes change

We acknowledge that it is difficult to give up something you have been doing for decades, so there is natural resistance by both patients and clinicians to move the Pap smear into a secondary role. But the data support primary HPV testing as the best screening option from a public health perspective.

At some point, hopefully soon, primary HPV testing will receive approval for self-sampling; this has the potential to reach patients in rural or remote locations who may otherwise not get screened for cervical cancer.¹³

The 2019 risk-based management guidelines from the ASCCP (American Society for Colposcopy and Cervical Pathology) also incorporate the use of HPV-based screening and surveillance after abnormal tests or colposcopy. Therefore, switching to primary HPV screening will not impact your ability to follow patients appropriately based on clinical guidelines.

Our advice to clinicians is to switch to primary HPV screening now if possible. If that is not feasible, continue your current strategy until you can make the change. And, of course, we recommend that you implement an HPV vaccination program in your practice to maximize primary prevention of HPV-related cancers. ●