Federal Practitioner

The scientific evidence for airborne transmission of the SARS-CoV-2 virus from different researchers all point in the same direction – that infectious aerosols are the principal means of person-to-person transmission, according to experts.

Not that it’s without controversy.

The science backing aerosol transmission “is clear-cut, but it is not accepted in many circles,” Trisha Greenhalgh, PhD, said in an interview.

“In particular, some in the evidence-based medicine movement and some infectious diseases clinicians are remarkably resistant to the evidence,” added Dr. Greenhalgh, professor of primary care health sciences at the University of Oxford (England).

“It’s very hard to see why, since the evidence all stacks up,” Dr. Greenhalgh said.

“The scientific evidence on spread from both near-field and far-field aerosols has been clear since early on in the pandemic, but there was resistance to acknowledging this in some circles, including the medical journals,” Joseph G. Allen, DSc, MPH, told this news organization when asked to comment.

“This is the week the dam broke. Three new commentaries came out … in top medical journals – BMJ, The Lancet, JAMA – all making the same point that aerosols are the dominant mode of transmission,” added Dr. Allen, associate professor of exposure assessment science at the Harvard T.H. Chan School of Public Health in Boston.

Dr. Greenhalgh and colleagues point to an increase in COVID-19 cases in the aftermath of so-called “super-spreader” events, spread of SARS-CoV-2 to people across different hotel rooms, and the relatively lower transmission detected after outdoor events.
 

Top 10 reasons

They outlined 10 scientific reasons backing airborne transmission in a commentary published online April 15 in The Lancet:

• The dominance of airborne transmission is supported by long-range transmission observed at super-spreader events.
• Long-range transmission has been reported among rooms at COVID-19 quarantine hotels, settings where infected people never spent time in the same room.
• Asymptomatic individuals account for an estimated 33%-59% of SARS-CoV-2 transmission, and could be spreading the virus through speaking, which produces thousands of aerosol particles and few large droplets.
• Transmission outdoors and in well-ventilated indoor spaces is lower than in enclosed spaces.
• Nosocomial infections are reported in health care settings where protective measures address large droplets but not aerosols.
• Viable SARS-CoV-2 has been detected in the air of hospital rooms and in the car of an infected person.
• Investigators found SARS-CoV-2 in hospital air filters and building ducts.
• It’s not just humans – infected animals can infect animals in other cages connected only through an air duct.
• No strong evidence refutes airborne transmission, and contact tracing supports secondary transmission in crowded, poorly ventilated indoor spaces.
• Only limited evidence supports other means of SARS-CoV-2 transmission, including through fomites or large droplets.

“We thought we’d summarize [the evidence] to clarify the arguments for and against. We looked hard for evidence against but found none,” Dr. Greenhalgh said.

“Although other routes can contribute, we believe that the airborne route is likely to be dominant,” the authors note.

The evidence on airborne transmission was there very early on but the Centers for Disease Control and Prevention, World Health Organization, and others repeated the message that the primary concern was droplets and fomites.
 

Response to a review

The top 10 list is also part rebuttal of a systematic review funded by the WHO and published last month that points to inconclusive evidence for airborne transmission. The researchers involved with that review state that “the lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission.”

However, Dr. Greenhalgh and colleagues note that “this conclusion, and the wide circulation of the review’s findings, is concerning because of the public health implications.”

The current authors also argue that enough evidence already exists on airborne transmission. “Policy should change. We don’t need more research on this topic; we need different policy,” Dr. Greenhalgh said. “We need ventilation front and center, air filtration when necessary, and better-fitting masks worn whenever indoors.”

Dr. Allen agreed that guidance hasn’t always kept pace with the science. “With all of the new evidence accumulated on airborne transmission since last winter, there is still widespread confusion in the public about modes of transmission,” he said. Dr. Allen also serves as commissioner of The Lancet COVID-19 Commission and is chair of the commission’s Task Force on Safe Work, Safe Schools, and Safe Travel.

“It was only just last week that CDC pulled back on guidance on ‘deep cleaning’ and in its place correctly said that the risk from touching surfaces is low,” he added. “The science has been clear on this for over a year, but official guidance was only recently updated.”

As a result, many companies and organizations continued to focus on “hygiene theatre,” Dr. Allen said, “wasting resources on overcleaning surfaces. Unbelievably, many schools still close for an entire day each week for deep cleaning and some still quarantine library books. The message that shared air is the problem, not shared surfaces, is a message that still needs to be reinforced.”

The National Institute for Health Research, Economic and Social Research Council, and Wellcome support Dr. Greenhalgh’s research. Dr. Greenhalgh and Dr. Allen had no relevant financial relationships to disclose.

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

The scientific evidence for airborne transmission of the SARS-CoV-2 virus from different researchers all point in the same direction – that infectious aerosols are the principal means of person-to-person transmission, according to experts.

Not that it’s without controversy.

The science backing aerosol transmission “is clear-cut, but it is not accepted in many circles,” Trisha Greenhalgh, PhD, said in an interview.

“In particular, some in the evidence-based medicine movement and some infectious diseases clinicians are remarkably resistant to the evidence,” added Dr. Greenhalgh, professor of primary care health sciences at the University of Oxford (England).

“It’s very hard to see why, since the evidence all stacks up,” Dr. Greenhalgh said.

“The scientific evidence on spread from both near-field and far-field aerosols has been clear since early on in the pandemic, but there was resistance to acknowledging this in some circles, including the medical journals,” Joseph G. Allen, DSc, MPH, told this news organization when asked to comment.

“This is the week the dam broke. Three new commentaries came out … in top medical journals – BMJ, The Lancet, JAMA – all making the same point that aerosols are the dominant mode of transmission,” added Dr. Allen, associate professor of exposure assessment science at the Harvard T.H. Chan School of Public Health in Boston.

Dr. Greenhalgh and colleagues point to an increase in COVID-19 cases in the aftermath of so-called “super-spreader” events, spread of SARS-CoV-2 to people across different hotel rooms, and the relatively lower transmission detected after outdoor events.
 

Top 10 reasons

They outlined 10 scientific reasons backing airborne transmission in a commentary published online April 15 in The Lancet:

• The dominance of airborne transmission is supported by long-range transmission observed at super-spreader events.
• Long-range transmission has been reported among rooms at COVID-19 quarantine hotels, settings where infected people never spent time in the same room.
• Asymptomatic individuals account for an estimated 33%-59% of SARS-CoV-2 transmission, and could be spreading the virus through speaking, which produces thousands of aerosol particles and few large droplets.
• Transmission outdoors and in well-ventilated indoor spaces is lower than in enclosed spaces.
• Nosocomial infections are reported in health care settings where protective measures address large droplets but not aerosols.
• Viable SARS-CoV-2 has been detected in the air of hospital rooms and in the car of an infected person.
• Investigators found SARS-CoV-2 in hospital air filters and building ducts.
• It’s not just humans – infected animals can infect animals in other cages connected only through an air duct.
• No strong evidence refutes airborne transmission, and contact tracing supports secondary transmission in crowded, poorly ventilated indoor spaces.
• Only limited evidence supports other means of SARS-CoV-2 transmission, including through fomites or large droplets.

“We thought we’d summarize [the evidence] to clarify the arguments for and against. We looked hard for evidence against but found none,” Dr. Greenhalgh said.

“Although other routes can contribute, we believe that the airborne route is likely to be dominant,” the authors note.

The evidence on airborne transmission was there very early on but the Centers for Disease Control and Prevention, World Health Organization, and others repeated the message that the primary concern was droplets and fomites.
 

Response to a review

The top 10 list is also part rebuttal of a systematic review funded by the WHO and published last month that points to inconclusive evidence for airborne transmission. The researchers involved with that review state that “the lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission.”

However, Dr. Greenhalgh and colleagues note that “this conclusion, and the wide circulation of the review’s findings, is concerning because of the public health implications.”

The current authors also argue that enough evidence already exists on airborne transmission. “Policy should change. We don’t need more research on this topic; we need different policy,” Dr. Greenhalgh said. “We need ventilation front and center, air filtration when necessary, and better-fitting masks worn whenever indoors.”

Dr. Allen agreed that guidance hasn’t always kept pace with the science. “With all of the new evidence accumulated on airborne transmission since last winter, there is still widespread confusion in the public about modes of transmission,” he said. Dr. Allen also serves as commissioner of The Lancet COVID-19 Commission and is chair of the commission’s Task Force on Safe Work, Safe Schools, and Safe Travel.

“It was only just last week that CDC pulled back on guidance on ‘deep cleaning’ and in its place correctly said that the risk from touching surfaces is low,” he added. “The science has been clear on this for over a year, but official guidance was only recently updated.”

As a result, many companies and organizations continued to focus on “hygiene theatre,” Dr. Allen said, “wasting resources on overcleaning surfaces. Unbelievably, many schools still close for an entire day each week for deep cleaning and some still quarantine library books. The message that shared air is the problem, not shared surfaces, is a message that still needs to be reinforced.”

The National Institute for Health Research, Economic and Social Research Council, and Wellcome support Dr. Greenhalgh’s research. Dr. Greenhalgh and Dr. Allen had no relevant financial relationships to disclose.

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

The scientific evidence for airborne transmission of the SARS-CoV-2 virus from different researchers all point in the same direction – that infectious aerosols are the principal means of person-to-person transmission, according to experts.

Not that it’s without controversy.

The science backing aerosol transmission “is clear-cut, but it is not accepted in many circles,” Trisha Greenhalgh, PhD, said in an interview.

“In particular, some in the evidence-based medicine movement and some infectious diseases clinicians are remarkably resistant to the evidence,” added Dr. Greenhalgh, professor of primary care health sciences at the University of Oxford (England).

“It’s very hard to see why, since the evidence all stacks up,” Dr. Greenhalgh said.

“The scientific evidence on spread from both near-field and far-field aerosols has been clear since early on in the pandemic, but there was resistance to acknowledging this in some circles, including the medical journals,” Joseph G. Allen, DSc, MPH, told this news organization when asked to comment.

“This is the week the dam broke. Three new commentaries came out … in top medical journals – BMJ, The Lancet, JAMA – all making the same point that aerosols are the dominant mode of transmission,” added Dr. Allen, associate professor of exposure assessment science at the Harvard T.H. Chan School of Public Health in Boston.

Dr. Greenhalgh and colleagues point to an increase in COVID-19 cases in the aftermath of so-called “super-spreader” events, spread of SARS-CoV-2 to people across different hotel rooms, and the relatively lower transmission detected after outdoor events.
 

Top 10 reasons

They outlined 10 scientific reasons backing airborne transmission in a commentary published online April 15 in The Lancet:

• The dominance of airborne transmission is supported by long-range transmission observed at super-spreader events.
• Long-range transmission has been reported among rooms at COVID-19 quarantine hotels, settings where infected people never spent time in the same room.
• Asymptomatic individuals account for an estimated 33%-59% of SARS-CoV-2 transmission, and could be spreading the virus through speaking, which produces thousands of aerosol particles and few large droplets.
• Transmission outdoors and in well-ventilated indoor spaces is lower than in enclosed spaces.
• Nosocomial infections are reported in health care settings where protective measures address large droplets but not aerosols.
• Viable SARS-CoV-2 has been detected in the air of hospital rooms and in the car of an infected person.
• Investigators found SARS-CoV-2 in hospital air filters and building ducts.
• It’s not just humans – infected animals can infect animals in other cages connected only through an air duct.
• No strong evidence refutes airborne transmission, and contact tracing supports secondary transmission in crowded, poorly ventilated indoor spaces.
• Only limited evidence supports other means of SARS-CoV-2 transmission, including through fomites or large droplets.

“We thought we’d summarize [the evidence] to clarify the arguments for and against. We looked hard for evidence against but found none,” Dr. Greenhalgh said.

“Although other routes can contribute, we believe that the airborne route is likely to be dominant,” the authors note.

The evidence on airborne transmission was there very early on but the Centers for Disease Control and Prevention, World Health Organization, and others repeated the message that the primary concern was droplets and fomites.
 

Response to a review

The top 10 list is also part rebuttal of a systematic review funded by the WHO and published last month that points to inconclusive evidence for airborne transmission. The researchers involved with that review state that “the lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission.”

However, Dr. Greenhalgh and colleagues note that “this conclusion, and the wide circulation of the review’s findings, is concerning because of the public health implications.”

The current authors also argue that enough evidence already exists on airborne transmission. “Policy should change. We don’t need more research on this topic; we need different policy,” Dr. Greenhalgh said. “We need ventilation front and center, air filtration when necessary, and better-fitting masks worn whenever indoors.”

Dr. Allen agreed that guidance hasn’t always kept pace with the science. “With all of the new evidence accumulated on airborne transmission since last winter, there is still widespread confusion in the public about modes of transmission,” he said. Dr. Allen also serves as commissioner of The Lancet COVID-19 Commission and is chair of the commission’s Task Force on Safe Work, Safe Schools, and Safe Travel.

“It was only just last week that CDC pulled back on guidance on ‘deep cleaning’ and in its place correctly said that the risk from touching surfaces is low,” he added. “The science has been clear on this for over a year, but official guidance was only recently updated.”

As a result, many companies and organizations continued to focus on “hygiene theatre,” Dr. Allen said, “wasting resources on overcleaning surfaces. Unbelievably, many schools still close for an entire day each week for deep cleaning and some still quarantine library books. The message that shared air is the problem, not shared surfaces, is a message that still needs to be reinforced.”

The National Institute for Health Research, Economic and Social Research Council, and Wellcome support Dr. Greenhalgh’s research. Dr. Greenhalgh and Dr. Allen had no relevant financial relationships to disclose.

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

When I was a medical student, I always found it gratifying when there was a unifying mechanism that explained the symptoms of a disease. Part of the reason I chose dermatology as a specialty was how frequently we are able to “see” these mechanisms in the skin, both clinically and histologically. VEXAS syndrome – which stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic – provides one of those explanations that satisfies my need to understand the cause of a disease. What’s even more interesting is that this condition is caused by a postzygotic somatic mutation, an apparently underrecognized cause of disease that we are just now beginning to understand. An example of a postzygotic somatic mutation causing a disease that we all learned about in medical school is paroxysmal nocturnal hemoglobinuria.
 

Using a “bottom-up” approach, researchers at the National Institutes of Health and in the United Kingdom identified 25 patients with somatic UBA1 mutations and noticed that they had strikingly similar autoinflammatory syndromes. UBA1 encodes ubiquitin E1, which is part of the pathway the breaks down proteins as part of the normal cellular machine. It is localized to the X chromosome, so all 25 affected patients were males, and most were aged between 40 and 70 years. These patients had an autoinflammatory syndrome characterized by fever, chondritis (similar to relapsing polychondritis), vasculitis, and neutrophilic dermatoses. Many patients also had features of myelodysplastic syndrome and plasma cell dyscrasia. The inflammatory pattern in this condition seems to show elevations in tumor necrosis factor, interleukin-6, and interferon-gamma.

So why is this syndrome relevant to dermatology? We are often asked to evaluate patients for neutrophilic dermatosis and vasculitis, and many affected patients had clinical and histologic findings compatible with polyarteritis nodosa and Sweet syndrome. When confronted with a neutrophilic dermatosis, we’ve all been taught to evaluate for myelodysplastic syndrome, which many of these patients appeared to have, at least on the surface. When bone marrow biopsies were done, the myeloid cell precursors that give rise to neutrophils were noted to have prominent cytoplasmic vacuoles, hence the “V” in VEXAS.

In reading the article describing 25 patients with this syndrome, which was published in the New England Journal of Medicine, I was struck by how refractory they were to treatment. Most patients had been treated with systemic steroids, multiple biologics, and several nonbiologic medications that are mainstays of treatment for neutrophilic dermatosis like dapsone and colchicine. I was fortunate enough to speak to Amanda Ombrello, MD, of the National Human Genome Research Institute, one of the lead authors of the paper, who drew my attention to the supplementary appendix, which showed the marked injection-site reactions some patients had to anakinra – yet another reason why a patient might end up in a dermatology clinic. In my mind, all of these features could be a clue to a diagnosis of VEXAS syndrome.

Many patients seemed to fare poorly, with 40% of patients dying before the completion of the study. When it comes to extremely rare diseases, it seems that the more physicians who are aware of the existence of a particular syndrome, the more likely it is a patient will come under our care and be correctly diagnosed.

Dr. Saardi is a dermatologist and internist, and is director of the inpatient dermatology service at the George Washington University Hospital, Washington. He has no disclosures.

When I was a medical student, I always found it gratifying when there was a unifying mechanism that explained the symptoms of a disease. Part of the reason I chose dermatology as a specialty was how frequently we are able to “see” these mechanisms in the skin, both clinically and histologically. VEXAS syndrome – which stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic – provides one of those explanations that satisfies my need to understand the cause of a disease. What’s even more interesting is that this condition is caused by a postzygotic somatic mutation, an apparently underrecognized cause of disease that we are just now beginning to understand. An example of a postzygotic somatic mutation causing a disease that we all learned about in medical school is paroxysmal nocturnal hemoglobinuria.
 

Using a “bottom-up” approach, researchers at the National Institutes of Health and in the United Kingdom identified 25 patients with somatic UBA1 mutations and noticed that they had strikingly similar autoinflammatory syndromes. UBA1 encodes ubiquitin E1, which is part of the pathway the breaks down proteins as part of the normal cellular machine. It is localized to the X chromosome, so all 25 affected patients were males, and most were aged between 40 and 70 years. These patients had an autoinflammatory syndrome characterized by fever, chondritis (similar to relapsing polychondritis), vasculitis, and neutrophilic dermatoses. Many patients also had features of myelodysplastic syndrome and plasma cell dyscrasia. The inflammatory pattern in this condition seems to show elevations in tumor necrosis factor, interleukin-6, and interferon-gamma.

So why is this syndrome relevant to dermatology? We are often asked to evaluate patients for neutrophilic dermatosis and vasculitis, and many affected patients had clinical and histologic findings compatible with polyarteritis nodosa and Sweet syndrome. When confronted with a neutrophilic dermatosis, we’ve all been taught to evaluate for myelodysplastic syndrome, which many of these patients appeared to have, at least on the surface. When bone marrow biopsies were done, the myeloid cell precursors that give rise to neutrophils were noted to have prominent cytoplasmic vacuoles, hence the “V” in VEXAS.

In reading the article describing 25 patients with this syndrome, which was published in the New England Journal of Medicine, I was struck by how refractory they were to treatment. Most patients had been treated with systemic steroids, multiple biologics, and several nonbiologic medications that are mainstays of treatment for neutrophilic dermatosis like dapsone and colchicine. I was fortunate enough to speak to Amanda Ombrello, MD, of the National Human Genome Research Institute, one of the lead authors of the paper, who drew my attention to the supplementary appendix, which showed the marked injection-site reactions some patients had to anakinra – yet another reason why a patient might end up in a dermatology clinic. In my mind, all of these features could be a clue to a diagnosis of VEXAS syndrome.

Many patients seemed to fare poorly, with 40% of patients dying before the completion of the study. When it comes to extremely rare diseases, it seems that the more physicians who are aware of the existence of a particular syndrome, the more likely it is a patient will come under our care and be correctly diagnosed.

Dr. Saardi is a dermatologist and internist, and is director of the inpatient dermatology service at the George Washington University Hospital, Washington. He has no disclosures.

When I was a medical student, I always found it gratifying when there was a unifying mechanism that explained the symptoms of a disease. Part of the reason I chose dermatology as a specialty was how frequently we are able to “see” these mechanisms in the skin, both clinically and histologically. VEXAS syndrome – which stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic – provides one of those explanations that satisfies my need to understand the cause of a disease. What’s even more interesting is that this condition is caused by a postzygotic somatic mutation, an apparently underrecognized cause of disease that we are just now beginning to understand. An example of a postzygotic somatic mutation causing a disease that we all learned about in medical school is paroxysmal nocturnal hemoglobinuria.
 

Using a “bottom-up” approach, researchers at the National Institutes of Health and in the United Kingdom identified 25 patients with somatic UBA1 mutations and noticed that they had strikingly similar autoinflammatory syndromes. UBA1 encodes ubiquitin E1, which is part of the pathway the breaks down proteins as part of the normal cellular machine. It is localized to the X chromosome, so all 25 affected patients were males, and most were aged between 40 and 70 years. These patients had an autoinflammatory syndrome characterized by fever, chondritis (similar to relapsing polychondritis), vasculitis, and neutrophilic dermatoses. Many patients also had features of myelodysplastic syndrome and plasma cell dyscrasia. The inflammatory pattern in this condition seems to show elevations in tumor necrosis factor, interleukin-6, and interferon-gamma.

So why is this syndrome relevant to dermatology? We are often asked to evaluate patients for neutrophilic dermatosis and vasculitis, and many affected patients had clinical and histologic findings compatible with polyarteritis nodosa and Sweet syndrome. When confronted with a neutrophilic dermatosis, we’ve all been taught to evaluate for myelodysplastic syndrome, which many of these patients appeared to have, at least on the surface. When bone marrow biopsies were done, the myeloid cell precursors that give rise to neutrophils were noted to have prominent cytoplasmic vacuoles, hence the “V” in VEXAS.

In reading the article describing 25 patients with this syndrome, which was published in the New England Journal of Medicine, I was struck by how refractory they were to treatment. Most patients had been treated with systemic steroids, multiple biologics, and several nonbiologic medications that are mainstays of treatment for neutrophilic dermatosis like dapsone and colchicine. I was fortunate enough to speak to Amanda Ombrello, MD, of the National Human Genome Research Institute, one of the lead authors of the paper, who drew my attention to the supplementary appendix, which showed the marked injection-site reactions some patients had to anakinra – yet another reason why a patient might end up in a dermatology clinic. In my mind, all of these features could be a clue to a diagnosis of VEXAS syndrome.

Many patients seemed to fare poorly, with 40% of patients dying before the completion of the study. When it comes to extremely rare diseases, it seems that the more physicians who are aware of the existence of a particular syndrome, the more likely it is a patient will come under our care and be correctly diagnosed.

Dr. Saardi is a dermatologist and internist, and is director of the inpatient dermatology service at the George Washington University Hospital, Washington. He has no disclosures.

Approximately three-quarters of Mohs surgeons recommended nicotinamide for prevention of keratinocyte carcinoma, in a survey of members of the American College of Mohs Surgeons.

Although nicotinamide, a vitamin B3 derivative, has been shown to reduce keratinocyte carcinoma (KC) in high-risk patients, it is not approved by the Food and Drug Administration for chemoprevention, and no safe upper limit has been established in clinical trials to date, wrote Sheena Desai of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.

The investigators emailed an anonymous 12-question survey to 1,500 members of the American College of Mohs Surgeons. Of the 170 who responded, 10 were excluded for discordant responses, leaving 160 participants whose replies were included in a multiple logistic regression analysis. The respondents were mainly U.S. board-certified dermatologists and Mohs surgeons (99.4% for both); 86.9% were in clinical practice, including 78.8% in private practice, according to the report of the results, published in Dermatologic Surgery.

Overall, 76.9% of the respondents said they recommended nicotinamide for preventing KC, and 20% said they had recommended nicotinamide to more than 100 patients in the past year. In addition, 45% of respondents reported patients who had been taking nicotinamide for 2 years or more. Overall, 63.8% of the respondents expressed no concerns about long-term safety of nicotinamide, compared with 28.1% who said they were uncertain about long-term safety. Those who expressed concern or uncertainty about long-term safety were significantly less likely to recommend nicotinamide for KC prevention in the past year (odds ratio, 0.30; 95% confidence interval [CI] 0.13-0.71). Clinicians with more than 10 years in practice were significantly less likely to recommend nicotinamide for chemoprevention (OR, 0.20; 95% CI 0.05-0.82).

The study findings were limited by several factors, including the low number of responses and the potential lack of generalizability to clinicians other than Mohs surgeons, the researchers noted. “Additional studies on nicotinamide safety and use patterns, including cost-effectiveness analyses, are needed given the widespread use identified in this study,” they concluded.

Limited safety data highlight research gaps

The study is particularly important at this time because nicotinamide has been increasingly used for KC chemoprevention since a randomized, controlled trial published in 2015 in the New England Journal of Medicine showed benefits, corresponding author Rebecca I. Hartman, MD, of the department of dermatology, Brigham and Women’s Hospital and Harvard University, Boston, said in an interview. That study of high-risk patients found that nicotinamide, 500 mg twice a day, was safe and effective in lowering the rates of new nonmelanoma skin cancers and AKs after 12 months .

“However, because this is not a prescription medication, but rather an OTC vitamin supplement, data on its use are not available,” she said.

Dr. Hartman said she was not surprised that nicotinamide is being used frequently by a majority of the survey respondents. “Most are using this if someone has two KCs over 2 years, which is a quite common occurrence,” she noted. However, “I was a bit surprised that nearly two-thirds had no safety concerns with long-term use, even though this has not been well-studied,” she added.

“Like anything we recommend, we must consider the risks and benefits,” Dr. Hartman said of nicotinamide. “Unfortunately, we don’t know the risks well, since this hasn’t been well-characterized with regular long-term use in these doses,” and more research is needed, she said. “The risks are likely low, as this is a vitamin that has been used for years in various OTC supplements,” she added. “However, there are some data showing slightly increased all-cause mortality with similar doses of a related medicine, niacin, in cardiovascular patients. For this reason, I recommend the medication when a patient’s KCs are really becoming burdensome – several KCs in a year or two – or when they are high-risk due to immunosuppression,” she explained.

“We also must consider the individual patient. For a healthy younger patient who has a public-facing job and as a result is very averse to developing any KCs on his or her face and very motivated to try prevention, it may make sense to try nicotinamide,” Dr. Hartman said. But for an older patient with cardiovascular comorbidities who is not bothered by a KC on his or her back or extremities, “this medication may not have a favorable risk-benefit profile.”

To address safety concerns, “researchers need to examine whether there are any harms in long-term regular nicotinamide use for KC prevention,” Dr. Hartman said. “This is something we hope to do in our patients; however, it is challenging to study in a retrospective way since the harm is likely small and there are so many other features that influence mortality as an outcome,” she noted.

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

Approximately three-quarters of Mohs surgeons recommended nicotinamide for prevention of keratinocyte carcinoma, in a survey of members of the American College of Mohs Surgeons.

Although nicotinamide, a vitamin B3 derivative, has been shown to reduce keratinocyte carcinoma (KC) in high-risk patients, it is not approved by the Food and Drug Administration for chemoprevention, and no safe upper limit has been established in clinical trials to date, wrote Sheena Desai of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.

The investigators emailed an anonymous 12-question survey to 1,500 members of the American College of Mohs Surgeons. Of the 170 who responded, 10 were excluded for discordant responses, leaving 160 participants whose replies were included in a multiple logistic regression analysis. The respondents were mainly U.S. board-certified dermatologists and Mohs surgeons (99.4% for both); 86.9% were in clinical practice, including 78.8% in private practice, according to the report of the results, published in Dermatologic Surgery.

Overall, 76.9% of the respondents said they recommended nicotinamide for preventing KC, and 20% said they had recommended nicotinamide to more than 100 patients in the past year. In addition, 45% of respondents reported patients who had been taking nicotinamide for 2 years or more. Overall, 63.8% of the respondents expressed no concerns about long-term safety of nicotinamide, compared with 28.1% who said they were uncertain about long-term safety. Those who expressed concern or uncertainty about long-term safety were significantly less likely to recommend nicotinamide for KC prevention in the past year (odds ratio, 0.30; 95% confidence interval [CI] 0.13-0.71). Clinicians with more than 10 years in practice were significantly less likely to recommend nicotinamide for chemoprevention (OR, 0.20; 95% CI 0.05-0.82).

The study findings were limited by several factors, including the low number of responses and the potential lack of generalizability to clinicians other than Mohs surgeons, the researchers noted. “Additional studies on nicotinamide safety and use patterns, including cost-effectiveness analyses, are needed given the widespread use identified in this study,” they concluded.

Limited safety data highlight research gaps

The study is particularly important at this time because nicotinamide has been increasingly used for KC chemoprevention since a randomized, controlled trial published in 2015 in the New England Journal of Medicine showed benefits, corresponding author Rebecca I. Hartman, MD, of the department of dermatology, Brigham and Women’s Hospital and Harvard University, Boston, said in an interview. That study of high-risk patients found that nicotinamide, 500 mg twice a day, was safe and effective in lowering the rates of new nonmelanoma skin cancers and AKs after 12 months .

“However, because this is not a prescription medication, but rather an OTC vitamin supplement, data on its use are not available,” she said.

Dr. Hartman said she was not surprised that nicotinamide is being used frequently by a majority of the survey respondents. “Most are using this if someone has two KCs over 2 years, which is a quite common occurrence,” she noted. However, “I was a bit surprised that nearly two-thirds had no safety concerns with long-term use, even though this has not been well-studied,” she added.

“Like anything we recommend, we must consider the risks and benefits,” Dr. Hartman said of nicotinamide. “Unfortunately, we don’t know the risks well, since this hasn’t been well-characterized with regular long-term use in these doses,” and more research is needed, she said. “The risks are likely low, as this is a vitamin that has been used for years in various OTC supplements,” she added. “However, there are some data showing slightly increased all-cause mortality with similar doses of a related medicine, niacin, in cardiovascular patients. For this reason, I recommend the medication when a patient’s KCs are really becoming burdensome – several KCs in a year or two – or when they are high-risk due to immunosuppression,” she explained.

“We also must consider the individual patient. For a healthy younger patient who has a public-facing job and as a result is very averse to developing any KCs on his or her face and very motivated to try prevention, it may make sense to try nicotinamide,” Dr. Hartman said. But for an older patient with cardiovascular comorbidities who is not bothered by a KC on his or her back or extremities, “this medication may not have a favorable risk-benefit profile.”

To address safety concerns, “researchers need to examine whether there are any harms in long-term regular nicotinamide use for KC prevention,” Dr. Hartman said. “This is something we hope to do in our patients; however, it is challenging to study in a retrospective way since the harm is likely small and there are so many other features that influence mortality as an outcome,” she noted.

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

Approximately three-quarters of Mohs surgeons recommended nicotinamide for prevention of keratinocyte carcinoma, in a survey of members of the American College of Mohs Surgeons.

Although nicotinamide, a vitamin B3 derivative, has been shown to reduce keratinocyte carcinoma (KC) in high-risk patients, it is not approved by the Food and Drug Administration for chemoprevention, and no safe upper limit has been established in clinical trials to date, wrote Sheena Desai of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.

The investigators emailed an anonymous 12-question survey to 1,500 members of the American College of Mohs Surgeons. Of the 170 who responded, 10 were excluded for discordant responses, leaving 160 participants whose replies were included in a multiple logistic regression analysis. The respondents were mainly U.S. board-certified dermatologists and Mohs surgeons (99.4% for both); 86.9% were in clinical practice, including 78.8% in private practice, according to the report of the results, published in Dermatologic Surgery.

Overall, 76.9% of the respondents said they recommended nicotinamide for preventing KC, and 20% said they had recommended nicotinamide to more than 100 patients in the past year. In addition, 45% of respondents reported patients who had been taking nicotinamide for 2 years or more. Overall, 63.8% of the respondents expressed no concerns about long-term safety of nicotinamide, compared with 28.1% who said they were uncertain about long-term safety. Those who expressed concern or uncertainty about long-term safety were significantly less likely to recommend nicotinamide for KC prevention in the past year (odds ratio, 0.30; 95% confidence interval [CI] 0.13-0.71). Clinicians with more than 10 years in practice were significantly less likely to recommend nicotinamide for chemoprevention (OR, 0.20; 95% CI 0.05-0.82).

The study findings were limited by several factors, including the low number of responses and the potential lack of generalizability to clinicians other than Mohs surgeons, the researchers noted. “Additional studies on nicotinamide safety and use patterns, including cost-effectiveness analyses, are needed given the widespread use identified in this study,” they concluded.

Limited safety data highlight research gaps

The study is particularly important at this time because nicotinamide has been increasingly used for KC chemoprevention since a randomized, controlled trial published in 2015 in the New England Journal of Medicine showed benefits, corresponding author Rebecca I. Hartman, MD, of the department of dermatology, Brigham and Women’s Hospital and Harvard University, Boston, said in an interview. That study of high-risk patients found that nicotinamide, 500 mg twice a day, was safe and effective in lowering the rates of new nonmelanoma skin cancers and AKs after 12 months .

“However, because this is not a prescription medication, but rather an OTC vitamin supplement, data on its use are not available,” she said.

Dr. Hartman said she was not surprised that nicotinamide is being used frequently by a majority of the survey respondents. “Most are using this if someone has two KCs over 2 years, which is a quite common occurrence,” she noted. However, “I was a bit surprised that nearly two-thirds had no safety concerns with long-term use, even though this has not been well-studied,” she added.

“Like anything we recommend, we must consider the risks and benefits,” Dr. Hartman said of nicotinamide. “Unfortunately, we don’t know the risks well, since this hasn’t been well-characterized with regular long-term use in these doses,” and more research is needed, she said. “The risks are likely low, as this is a vitamin that has been used for years in various OTC supplements,” she added. “However, there are some data showing slightly increased all-cause mortality with similar doses of a related medicine, niacin, in cardiovascular patients. For this reason, I recommend the medication when a patient’s KCs are really becoming burdensome – several KCs in a year or two – or when they are high-risk due to immunosuppression,” she explained.

“We also must consider the individual patient. For a healthy younger patient who has a public-facing job and as a result is very averse to developing any KCs on his or her face and very motivated to try prevention, it may make sense to try nicotinamide,” Dr. Hartman said. But for an older patient with cardiovascular comorbidities who is not bothered by a KC on his or her back or extremities, “this medication may not have a favorable risk-benefit profile.”

To address safety concerns, “researchers need to examine whether there are any harms in long-term regular nicotinamide use for KC prevention,” Dr. Hartman said. “This is something we hope to do in our patients; however, it is challenging to study in a retrospective way since the harm is likely small and there are so many other features that influence mortality as an outcome,” she noted.

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

Myoclonus was diagnosed in about half of hospitalized COVID-19 patients who were evaluated for movement disorders, data from 50 cases show.

Abnormal movements often occur as complications from critical illness, and neurologic consultation can determine whether patients have experienced a seizure or stroke. However, restriction of bedside assessment in the wake of the COVID-19 pandemic increases the risk that abnormal movements will be missed, Jeffrey R. Clark and Eric M. Liotta, MD, of Northwestern University, Chicago, and colleagues wrote.

“Given the limited reports of abnormal movements in hospitalized COVID-19 patients and increased recognition of neurologic manifestations of COVID-19, we sought to examine the frequency and etiology of this finding as an indication of neurologic consultation,” they said.

In a study published in the Journal of the Neurological Sciences, the researchers reviewed data from the first 50 consecutive patients with COVID-19 symptoms who were hospitalized at a single center and underwent neurologic consultation between March 17, 2020, and May 18, 2020.

Overall, 11 patients (22.0%) of patients experienced abnormal movement, and all were admitted to the ICU within 7 days of meeting criteria for severe COVID-19. These patients included nine men and two women with an age range of 36-78 years. The most common comorbidities were obesity, hypertension, diabetes, chronic kidney disease, and coronary artery disease.

Myoclonus (generalized and focal) was the most common abnormal movement, and present in 6 of the 11 patients. Three cases were attributed to high-intensity sedation, and three to toxic-metabolic disturbances. In two patients, abnormal movements were attributed to focal seizures in the setting of encephalopathy, with focal facial twitching. An additional two patients experienced tremors; one showed an acute subdural hemorrhage on CT imaging. The second patient showed no sign of stroke or other abnormality on MRI and the tremor improved during the hospital stay. One patient who experienced abnormal high-amplitude nonrhythmic movements of the lower extremities was diagnosed with serotonin syndrome that resolved after discontinuing high-dose fentanyl.

The study findings were limited by several factors, including the small study population and limited availability of MRI, the researchers noted. Assessing severe COVID-19 cases in the ICU setting presents a challenge because of limited patient participation and the potentially confounding effects of sedation and mechanical ventilation.

However, the results highlight the importance of bedside consultation for neurologic evaluation to implement timely, directed treatments, the researchers said.

“A heightened awareness of abnormal eye movements, or subtle facial tremoring, may be the first steps in recognizing potentially dangerous neurologic manifestations,” and clinicians caring for patients with severe COVID-19 should be able to recognize abnormal movements and seek neurologic consultation when indicated, they emphasized.

The study was supported in part by grants to coauthors Nicholas J. Reish, MD, and Dr. Liotta from the National Institutes of Health. The researchers had no financial conflicts to disclose.

Myoclonus was diagnosed in about half of hospitalized COVID-19 patients who were evaluated for movement disorders, data from 50 cases show.

Abnormal movements often occur as complications from critical illness, and neurologic consultation can determine whether patients have experienced a seizure or stroke. However, restriction of bedside assessment in the wake of the COVID-19 pandemic increases the risk that abnormal movements will be missed, Jeffrey R. Clark and Eric M. Liotta, MD, of Northwestern University, Chicago, and colleagues wrote.

“Given the limited reports of abnormal movements in hospitalized COVID-19 patients and increased recognition of neurologic manifestations of COVID-19, we sought to examine the frequency and etiology of this finding as an indication of neurologic consultation,” they said.

In a study published in the Journal of the Neurological Sciences, the researchers reviewed data from the first 50 consecutive patients with COVID-19 symptoms who were hospitalized at a single center and underwent neurologic consultation between March 17, 2020, and May 18, 2020.

Overall, 11 patients (22.0%) of patients experienced abnormal movement, and all were admitted to the ICU within 7 days of meeting criteria for severe COVID-19. These patients included nine men and two women with an age range of 36-78 years. The most common comorbidities were obesity, hypertension, diabetes, chronic kidney disease, and coronary artery disease.

Myoclonus (generalized and focal) was the most common abnormal movement, and present in 6 of the 11 patients. Three cases were attributed to high-intensity sedation, and three to toxic-metabolic disturbances. In two patients, abnormal movements were attributed to focal seizures in the setting of encephalopathy, with focal facial twitching. An additional two patients experienced tremors; one showed an acute subdural hemorrhage on CT imaging. The second patient showed no sign of stroke or other abnormality on MRI and the tremor improved during the hospital stay. One patient who experienced abnormal high-amplitude nonrhythmic movements of the lower extremities was diagnosed with serotonin syndrome that resolved after discontinuing high-dose fentanyl.

The study findings were limited by several factors, including the small study population and limited availability of MRI, the researchers noted. Assessing severe COVID-19 cases in the ICU setting presents a challenge because of limited patient participation and the potentially confounding effects of sedation and mechanical ventilation.

However, the results highlight the importance of bedside consultation for neurologic evaluation to implement timely, directed treatments, the researchers said.

“A heightened awareness of abnormal eye movements, or subtle facial tremoring, may be the first steps in recognizing potentially dangerous neurologic manifestations,” and clinicians caring for patients with severe COVID-19 should be able to recognize abnormal movements and seek neurologic consultation when indicated, they emphasized.

The study was supported in part by grants to coauthors Nicholas J. Reish, MD, and Dr. Liotta from the National Institutes of Health. The researchers had no financial conflicts to disclose.

Myoclonus was diagnosed in about half of hospitalized COVID-19 patients who were evaluated for movement disorders, data from 50 cases show.

Abnormal movements often occur as complications from critical illness, and neurologic consultation can determine whether patients have experienced a seizure or stroke. However, restriction of bedside assessment in the wake of the COVID-19 pandemic increases the risk that abnormal movements will be missed, Jeffrey R. Clark and Eric M. Liotta, MD, of Northwestern University, Chicago, and colleagues wrote.

“Given the limited reports of abnormal movements in hospitalized COVID-19 patients and increased recognition of neurologic manifestations of COVID-19, we sought to examine the frequency and etiology of this finding as an indication of neurologic consultation,” they said.

In a study published in the Journal of the Neurological Sciences, the researchers reviewed data from the first 50 consecutive patients with COVID-19 symptoms who were hospitalized at a single center and underwent neurologic consultation between March 17, 2020, and May 18, 2020.

Overall, 11 patients (22.0%) of patients experienced abnormal movement, and all were admitted to the ICU within 7 days of meeting criteria for severe COVID-19. These patients included nine men and two women with an age range of 36-78 years. The most common comorbidities were obesity, hypertension, diabetes, chronic kidney disease, and coronary artery disease.

Myoclonus (generalized and focal) was the most common abnormal movement, and present in 6 of the 11 patients. Three cases were attributed to high-intensity sedation, and three to toxic-metabolic disturbances. In two patients, abnormal movements were attributed to focal seizures in the setting of encephalopathy, with focal facial twitching. An additional two patients experienced tremors; one showed an acute subdural hemorrhage on CT imaging. The second patient showed no sign of stroke or other abnormality on MRI and the tremor improved during the hospital stay. One patient who experienced abnormal high-amplitude nonrhythmic movements of the lower extremities was diagnosed with serotonin syndrome that resolved after discontinuing high-dose fentanyl.

The study findings were limited by several factors, including the small study population and limited availability of MRI, the researchers noted. Assessing severe COVID-19 cases in the ICU setting presents a challenge because of limited patient participation and the potentially confounding effects of sedation and mechanical ventilation.

However, the results highlight the importance of bedside consultation for neurologic evaluation to implement timely, directed treatments, the researchers said.

“A heightened awareness of abnormal eye movements, or subtle facial tremoring, may be the first steps in recognizing potentially dangerous neurologic manifestations,” and clinicians caring for patients with severe COVID-19 should be able to recognize abnormal movements and seek neurologic consultation when indicated, they emphasized.

The study was supported in part by grants to coauthors Nicholas J. Reish, MD, and Dr. Liotta from the National Institutes of Health. The researchers had no financial conflicts to disclose.

Among U.S. patients who regularly undergo hemodialysis, 20% had some degree of hesitancy about receiving a COVID-19 vaccine in a survey of 1,515 patients conducted during January and February 2021.
 

The most frequently cited concern associated with hesitancy over vaccination against the SARS-CoV-2 virus was with regard to possible adverse effects. This was cited by more than half of the patients who were concerned about being vaccinated.

Hesitancy rates were highest among people aged 44 years or younger, women, people who identified as non-Hispanic Black or non-Hispanic other (generally Native American or Pacific Islander), those with less than some college education, and those without a history of influenza vaccination, Pablo Garcia, MD, reported at the National Kidney Foundation (NKF) 2021 Spring Clinical Meetings.
 

Hesitancy or access?

Overall, however, the findings suggest that the main barrier to COVID-19 vaccine uptake is “access rather than hesitancy,” explained Dr. Garcia, a nephrologist at Stanford (Calif.) University. He predicts that this barrier will soon resolve, in part because of a Centers for Disease Control and Prevention program launched in March 2021 that is supplying COVID-19 vaccine to U.S. dialysis centers to administer to their patients.

“This will facilitate access to the vaccine” for patients who regularly receive hemodialysis, Dr. Garcia said during his presentation.

“Administering vaccines in dialysis clinics will help. Patients are already accustomed to receiving influenza vaccine in the clinic,” said Joseph A. Vassalotti, MD, a nephrologist at Mount Sinai Hospital, New York, and chief medical officer for the NKF.

Dr. Vassalotti cited the importance of protecting the vulnerable population of people who regularly receive hemodialysis. Among those patients, there was a 37% spike in all-cause mortality during peak weeks of the pandemic compared with similar periods during 2017-2019.
 

Any level of vaccine hesitancy is concerning

In an interview, he said, “Vaccination is the key to reducing this burden, so any level of vaccine hesitancy is concerning” with regard to patients who regularly undergo dialysis.

Hesitancy among patients who undergo dialysis appears to be less than in the general U.S. population, according to a series of surveys conducted from April through December 2020. In that series, hesitancy rates approached 50% in a sample of more than 8,000 people.

Hesitancy among people overall may have recently increased, at least for the short term, because of concerns over rare thrombotic events among people who receive certain types of COVID-19 vaccine, Dr. Vassalotti noted.

Dr. Garcia and associates conducted their survey from Jan. 8 to Feb. 11, 2021, among patients who regularly received hemodialysis at any of 150 randomly selected dialysis clinics that treat 30 or more patients and are managed by U.S. Renal Care. The study enrolled patients in 22 states. Most of the patients were aged 45-79 years; 30% were non-Hispanic White; 30% were Black, and 24% were Hispanic. The survey included 24 questions and took about 10 minutes to complete.

In reply to the statement, “If COVID-19 vaccine was proven safe and effective for the general population I would seek to get it,” 20% gave a reply of definitely not, probably not, or unsure; 79% answered either probably or definitely yes.

Another question asked about willingness to receive a vaccine if it was shown to be safe and effective for people receiving dialysis. In answer to that question, 19% said definitely not, probably not, or unsure.
 

Possible adverse effects an issue

Asked the reason why they were hesitant to receive the vaccine, 53% cited possible adverse effects; 19% cited general unease about vaccines; 19% said they did not think the COVID-19 vaccines would work; 17% said they did not think they needed a COVID-19 vaccine; and 15% said they had read or heard that COVID-19 vaccines were dangerous.

A set of questions asked survey respondents about their primary source of information about COVID-19 vaccines. About three-quarters cited television news; about 35% cited members of their dialysis clinic staff; about 30% cited friends and family; 20% cited social media; 20% cited their nephrologists; and roughly 15% cited newspapers.

The results suggest that potentially effective interventions to promote vaccine uptake include showing informational videos to patients during dialysis sessions and encouraging the staff at dialysis centers to proactively educate patients about COVID-19 vaccines and to promote uptake, suggest Dr. Garcia and Dr. Vassalotti.

Dr. Vassalotti noted that in a recent single-center survey of 90 U.S. patients undergoing hemodialysis that included 75 (85%) Black persons, the prevalence of hesitancy about COVID-19 vaccines was 50%. Hesitancy was often linked with gaps in patient education.

“We need broad educational measures, as well as targeting specific demographic groups” among whom the level of hesitancy is high, said Dr. Vassalotti.

He noted that patients who undergo dialysis are receptive to messages from dialysis clinic staff members and that this offers an “opportunity to understand misconceptions that underlie hesitancy and address them on an individual basis.”

The NKF has prepared a fact sheet for educating patients with kidney disease about the efficacy and safety of COVID-19 vaccines, Dr. Vassalotti noted.

Dr. Garcia has disclosed no relevant financial relationships. Dr. Vassalotti is an adviser and consultant to Renalytix AI and is a consultant to Janssen.

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

Among U.S. patients who regularly undergo hemodialysis, 20% had some degree of hesitancy about receiving a COVID-19 vaccine in a survey of 1,515 patients conducted during January and February 2021.
 

The most frequently cited concern associated with hesitancy over vaccination against the SARS-CoV-2 virus was with regard to possible adverse effects. This was cited by more than half of the patients who were concerned about being vaccinated.

Hesitancy rates were highest among people aged 44 years or younger, women, people who identified as non-Hispanic Black or non-Hispanic other (generally Native American or Pacific Islander), those with less than some college education, and those without a history of influenza vaccination, Pablo Garcia, MD, reported at the National Kidney Foundation (NKF) 2021 Spring Clinical Meetings.
 

Hesitancy or access?

Overall, however, the findings suggest that the main barrier to COVID-19 vaccine uptake is “access rather than hesitancy,” explained Dr. Garcia, a nephrologist at Stanford (Calif.) University. He predicts that this barrier will soon resolve, in part because of a Centers for Disease Control and Prevention program launched in March 2021 that is supplying COVID-19 vaccine to U.S. dialysis centers to administer to their patients.

“This will facilitate access to the vaccine” for patients who regularly receive hemodialysis, Dr. Garcia said during his presentation.

“Administering vaccines in dialysis clinics will help. Patients are already accustomed to receiving influenza vaccine in the clinic,” said Joseph A. Vassalotti, MD, a nephrologist at Mount Sinai Hospital, New York, and chief medical officer for the NKF.

Dr. Vassalotti cited the importance of protecting the vulnerable population of people who regularly receive hemodialysis. Among those patients, there was a 37% spike in all-cause mortality during peak weeks of the pandemic compared with similar periods during 2017-2019.
 

Any level of vaccine hesitancy is concerning

In an interview, he said, “Vaccination is the key to reducing this burden, so any level of vaccine hesitancy is concerning” with regard to patients who regularly undergo dialysis.

Hesitancy among patients who undergo dialysis appears to be less than in the general U.S. population, according to a series of surveys conducted from April through December 2020. In that series, hesitancy rates approached 50% in a sample of more than 8,000 people.

Hesitancy among people overall may have recently increased, at least for the short term, because of concerns over rare thrombotic events among people who receive certain types of COVID-19 vaccine, Dr. Vassalotti noted.

Dr. Garcia and associates conducted their survey from Jan. 8 to Feb. 11, 2021, among patients who regularly received hemodialysis at any of 150 randomly selected dialysis clinics that treat 30 or more patients and are managed by U.S. Renal Care. The study enrolled patients in 22 states. Most of the patients were aged 45-79 years; 30% were non-Hispanic White; 30% were Black, and 24% were Hispanic. The survey included 24 questions and took about 10 minutes to complete.

In reply to the statement, “If COVID-19 vaccine was proven safe and effective for the general population I would seek to get it,” 20% gave a reply of definitely not, probably not, or unsure; 79% answered either probably or definitely yes.

Another question asked about willingness to receive a vaccine if it was shown to be safe and effective for people receiving dialysis. In answer to that question, 19% said definitely not, probably not, or unsure.
 

Possible adverse effects an issue

Asked the reason why they were hesitant to receive the vaccine, 53% cited possible adverse effects; 19% cited general unease about vaccines; 19% said they did not think the COVID-19 vaccines would work; 17% said they did not think they needed a COVID-19 vaccine; and 15% said they had read or heard that COVID-19 vaccines were dangerous.

A set of questions asked survey respondents about their primary source of information about COVID-19 vaccines. About three-quarters cited television news; about 35% cited members of their dialysis clinic staff; about 30% cited friends and family; 20% cited social media; 20% cited their nephrologists; and roughly 15% cited newspapers.

The results suggest that potentially effective interventions to promote vaccine uptake include showing informational videos to patients during dialysis sessions and encouraging the staff at dialysis centers to proactively educate patients about COVID-19 vaccines and to promote uptake, suggest Dr. Garcia and Dr. Vassalotti.

Dr. Vassalotti noted that in a recent single-center survey of 90 U.S. patients undergoing hemodialysis that included 75 (85%) Black persons, the prevalence of hesitancy about COVID-19 vaccines was 50%. Hesitancy was often linked with gaps in patient education.

“We need broad educational measures, as well as targeting specific demographic groups” among whom the level of hesitancy is high, said Dr. Vassalotti.

He noted that patients who undergo dialysis are receptive to messages from dialysis clinic staff members and that this offers an “opportunity to understand misconceptions that underlie hesitancy and address them on an individual basis.”

The NKF has prepared a fact sheet for educating patients with kidney disease about the efficacy and safety of COVID-19 vaccines, Dr. Vassalotti noted.

Dr. Garcia has disclosed no relevant financial relationships. Dr. Vassalotti is an adviser and consultant to Renalytix AI and is a consultant to Janssen.

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

Among U.S. patients who regularly undergo hemodialysis, 20% had some degree of hesitancy about receiving a COVID-19 vaccine in a survey of 1,515 patients conducted during January and February 2021.
 

The most frequently cited concern associated with hesitancy over vaccination against the SARS-CoV-2 virus was with regard to possible adverse effects. This was cited by more than half of the patients who were concerned about being vaccinated.

Hesitancy rates were highest among people aged 44 years or younger, women, people who identified as non-Hispanic Black or non-Hispanic other (generally Native American or Pacific Islander), those with less than some college education, and those without a history of influenza vaccination, Pablo Garcia, MD, reported at the National Kidney Foundation (NKF) 2021 Spring Clinical Meetings.
 

Hesitancy or access?

Overall, however, the findings suggest that the main barrier to COVID-19 vaccine uptake is “access rather than hesitancy,” explained Dr. Garcia, a nephrologist at Stanford (Calif.) University. He predicts that this barrier will soon resolve, in part because of a Centers for Disease Control and Prevention program launched in March 2021 that is supplying COVID-19 vaccine to U.S. dialysis centers to administer to their patients.

“This will facilitate access to the vaccine” for patients who regularly receive hemodialysis, Dr. Garcia said during his presentation.

“Administering vaccines in dialysis clinics will help. Patients are already accustomed to receiving influenza vaccine in the clinic,” said Joseph A. Vassalotti, MD, a nephrologist at Mount Sinai Hospital, New York, and chief medical officer for the NKF.

Dr. Vassalotti cited the importance of protecting the vulnerable population of people who regularly receive hemodialysis. Among those patients, there was a 37% spike in all-cause mortality during peak weeks of the pandemic compared with similar periods during 2017-2019.
 

Any level of vaccine hesitancy is concerning

In an interview, he said, “Vaccination is the key to reducing this burden, so any level of vaccine hesitancy is concerning” with regard to patients who regularly undergo dialysis.

Hesitancy among patients who undergo dialysis appears to be less than in the general U.S. population, according to a series of surveys conducted from April through December 2020. In that series, hesitancy rates approached 50% in a sample of more than 8,000 people.

Hesitancy among people overall may have recently increased, at least for the short term, because of concerns over rare thrombotic events among people who receive certain types of COVID-19 vaccine, Dr. Vassalotti noted.

Dr. Garcia and associates conducted their survey from Jan. 8 to Feb. 11, 2021, among patients who regularly received hemodialysis at any of 150 randomly selected dialysis clinics that treat 30 or more patients and are managed by U.S. Renal Care. The study enrolled patients in 22 states. Most of the patients were aged 45-79 years; 30% were non-Hispanic White; 30% were Black, and 24% were Hispanic. The survey included 24 questions and took about 10 minutes to complete.

In reply to the statement, “If COVID-19 vaccine was proven safe and effective for the general population I would seek to get it,” 20% gave a reply of definitely not, probably not, or unsure; 79% answered either probably or definitely yes.

Another question asked about willingness to receive a vaccine if it was shown to be safe and effective for people receiving dialysis. In answer to that question, 19% said definitely not, probably not, or unsure.
 

Possible adverse effects an issue

Asked the reason why they were hesitant to receive the vaccine, 53% cited possible adverse effects; 19% cited general unease about vaccines; 19% said they did not think the COVID-19 vaccines would work; 17% said they did not think they needed a COVID-19 vaccine; and 15% said they had read or heard that COVID-19 vaccines were dangerous.

A set of questions asked survey respondents about their primary source of information about COVID-19 vaccines. About three-quarters cited television news; about 35% cited members of their dialysis clinic staff; about 30% cited friends and family; 20% cited social media; 20% cited their nephrologists; and roughly 15% cited newspapers.

The results suggest that potentially effective interventions to promote vaccine uptake include showing informational videos to patients during dialysis sessions and encouraging the staff at dialysis centers to proactively educate patients about COVID-19 vaccines and to promote uptake, suggest Dr. Garcia and Dr. Vassalotti.

Dr. Vassalotti noted that in a recent single-center survey of 90 U.S. patients undergoing hemodialysis that included 75 (85%) Black persons, the prevalence of hesitancy about COVID-19 vaccines was 50%. Hesitancy was often linked with gaps in patient education.

“We need broad educational measures, as well as targeting specific demographic groups” among whom the level of hesitancy is high, said Dr. Vassalotti.

He noted that patients who undergo dialysis are receptive to messages from dialysis clinic staff members and that this offers an “opportunity to understand misconceptions that underlie hesitancy and address them on an individual basis.”

The NKF has prepared a fact sheet for educating patients with kidney disease about the efficacy and safety of COVID-19 vaccines, Dr. Vassalotti noted.

Dr. Garcia has disclosed no relevant financial relationships. Dr. Vassalotti is an adviser and consultant to Renalytix AI and is a consultant to Janssen.

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

Patients with heart failure get pneumonia at a rate almost three times greater than expected and, once they do get pneumonia, have about a fourfold greater risk of death, investigators for a retrospective analysis of 13,000 patients from two landmark randomized HF trials have found.

Catherine Hackett/MDedge News

The investigators also found that HF patients with preserved ejection fraction (HFpEF) are at the highest risk of developing pneumonia. The findings underscore the importance of patients with HF getting a pneumonia vaccination, they found.

The analysis showed that 6.3% of patients in the PARADIGM-HF trial and 10.6% of those in the PARAGON-HF trial developed pneumonia, reported the study authors, led by John J.V. McMurray, MD, of the British Heart Foundation Cardiovascular Research Center at the University of Glasgow in Scotland (J Am Coll Cardiol. 2021;77:1961-73).

“The main reason for doing this study was the fact that many heart failure patients are not vaccinated, as they should be, against pneumonia – both pneumococcus and influenza vaccination,” Dr. McMurray said in an interview. “We wanted to document the frequency and consequences of pneumonia in patients with heart failure to help highlight this deficiency in care.”

Dr. McMurray said he believes this is the first study to document the incidence of pneumonia and pneumonia-related outcomes according to the two major ejection fraction phenotypes.
 

PARADIGM-HF and PARAGON-HF

The post hoc analysis consisted of 8,399 patients with HF with reduced ejection fraction (HFrEF) in PARADIGM-HF (Eur J Heart Fail. 2013 Sep;15[9]:1062-73) and 4,796 patients with HFpEF in PARAGON-HF (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The analysis focused on the 528 and 510 patients in each study, respectively, who developed pneumonia. Those rates translated to an incidence rate of 29 per 1,000 patient-years (95% confidence interval, 27-31) in PARADIGM-HF and 39 per 1,000 patient-years (95% CI, 36-42) in PARAGON-HF.

After pneumonia, the risk of death in patients increased substantially. In PARADIGM-HF, the adjusted hazard ratio for the risk of death from any cause after pneumonia was 4.34 (95% CI, 3.73-5.05). In PARAGON-HF, it was 3.76 (95% CI, 3.09-4.58). HF patients who contracted pneumonia also tended to have HF longer than their counterparts who didn’t develop pneumonia, but the frequency of previous hospitalization for HF didn’t vary between the pneumonia and no-pneumonia groups.

Patients who developed pneumonia tended to be older (average age of 66.9 years vs. 64.6 years, P < .001) and male (83.9% vs. 77.8%, P < .001). The mean age of patients in PARADIGM-HF was almost a decade younger than those in PARAGON-HF, 64 vs. 73 years.

Pneumonia patients also had worse Kansas City Cardiomyopathy Questionnaire scores (76 vs. 80 on average), but no difference in New York Heart Association functional class. “In general, patients who developed pneumonia had more symptoms and signs and HF than those who did not develop pneumonia,” Dr. McMurray and colleagues wrote.

Pneumonia patients also had higher rates of chronic obstructive pulmonary disease (26% vs. 12%), diabetes (43% vs. 34%), and atrial fibrillation (46% vs. 36%).

Another reason for conducting the study, Dr. McMurray said, “was the prior findings in patients with coronary disease and acute myocardial infarction that the risk associated with an episode of pneumonia [e.g., in subsequent vascular events and deaths] persisted long after the acute event. We wanted to see if this was also the case for heart failure, and indeed it was.”

For example, the adjusted HR for cardiovascular death or hospitalization in the first month following an episode of pneumonia was 9.48 (range of 6.85-13.12, P < .001), leveling off to 1.59 after 3 months or more.
 

Vaccination crucial in HF patients

Dr. McMurray noted that this study emphasizes the importance of pneumonia vaccination for patients with HF. “Given that we have so few treatments to offer patients with HFpEF, this makes the potential value of vaccination in these patients all the greater,” he said.

The COVID-19 pandemic, Dr. McMurray said, is a “good reminder of the dangers of a respiratory infection and the importance of vaccination in these patients. COVID-19 has interesting parallels in being a systemic disease and one with postacute, persisting effects.”

The persistent risk for adverse cardiovascular events 3 months and later after pneumonia is a novel finding of the study, wrote Donna Mancini, MD, and Gregory Gibson, MD, in an invited commentary (J Am Coll Cardiol. 2021;77:1974-6). Both are with the Icahn School of Medicine at Mt. Sinai in New York. The post hoc study also “serves as an important reminder” of pneumonia risk in patients with HF, especially during the pandemic, they wrote.

“Although vaccination alone appears unlikely to be a panacea, it is a readily accessible tool for mitigating disease severity and improving outcomes,” Dr. Mancini and Dr. Gibson wrote. “After all, an ounce of prevention is worth a pound of cure.”

Novartis provided funding for the PARADIGM-HF and PARAGON-HF trials, and Dr. McMurray and coauthors disclosed financial relationships with Novartis. Dr. Mancini and Dr. Gibson have no relevant financial relationships to disclose.

Patients with heart failure get pneumonia at a rate almost three times greater than expected and, once they do get pneumonia, have about a fourfold greater risk of death, investigators for a retrospective analysis of 13,000 patients from two landmark randomized HF trials have found.

Catherine Hackett/MDedge News

The investigators also found that HF patients with preserved ejection fraction (HFpEF) are at the highest risk of developing pneumonia. The findings underscore the importance of patients with HF getting a pneumonia vaccination, they found.

The analysis showed that 6.3% of patients in the PARADIGM-HF trial and 10.6% of those in the PARAGON-HF trial developed pneumonia, reported the study authors, led by John J.V. McMurray, MD, of the British Heart Foundation Cardiovascular Research Center at the University of Glasgow in Scotland (J Am Coll Cardiol. 2021;77:1961-73).

“The main reason for doing this study was the fact that many heart failure patients are not vaccinated, as they should be, against pneumonia – both pneumococcus and influenza vaccination,” Dr. McMurray said in an interview. “We wanted to document the frequency and consequences of pneumonia in patients with heart failure to help highlight this deficiency in care.”

Dr. McMurray said he believes this is the first study to document the incidence of pneumonia and pneumonia-related outcomes according to the two major ejection fraction phenotypes.
 

PARADIGM-HF and PARAGON-HF

The post hoc analysis consisted of 8,399 patients with HF with reduced ejection fraction (HFrEF) in PARADIGM-HF (Eur J Heart Fail. 2013 Sep;15[9]:1062-73) and 4,796 patients with HFpEF in PARAGON-HF (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The analysis focused on the 528 and 510 patients in each study, respectively, who developed pneumonia. Those rates translated to an incidence rate of 29 per 1,000 patient-years (95% confidence interval, 27-31) in PARADIGM-HF and 39 per 1,000 patient-years (95% CI, 36-42) in PARAGON-HF.

After pneumonia, the risk of death in patients increased substantially. In PARADIGM-HF, the adjusted hazard ratio for the risk of death from any cause after pneumonia was 4.34 (95% CI, 3.73-5.05). In PARAGON-HF, it was 3.76 (95% CI, 3.09-4.58). HF patients who contracted pneumonia also tended to have HF longer than their counterparts who didn’t develop pneumonia, but the frequency of previous hospitalization for HF didn’t vary between the pneumonia and no-pneumonia groups.

Patients who developed pneumonia tended to be older (average age of 66.9 years vs. 64.6 years, P < .001) and male (83.9% vs. 77.8%, P < .001). The mean age of patients in PARADIGM-HF was almost a decade younger than those in PARAGON-HF, 64 vs. 73 years.

Pneumonia patients also had worse Kansas City Cardiomyopathy Questionnaire scores (76 vs. 80 on average), but no difference in New York Heart Association functional class. “In general, patients who developed pneumonia had more symptoms and signs and HF than those who did not develop pneumonia,” Dr. McMurray and colleagues wrote.

Pneumonia patients also had higher rates of chronic obstructive pulmonary disease (26% vs. 12%), diabetes (43% vs. 34%), and atrial fibrillation (46% vs. 36%).

Another reason for conducting the study, Dr. McMurray said, “was the prior findings in patients with coronary disease and acute myocardial infarction that the risk associated with an episode of pneumonia [e.g., in subsequent vascular events and deaths] persisted long after the acute event. We wanted to see if this was also the case for heart failure, and indeed it was.”

For example, the adjusted HR for cardiovascular death or hospitalization in the first month following an episode of pneumonia was 9.48 (range of 6.85-13.12, P < .001), leveling off to 1.59 after 3 months or more.
 

Vaccination crucial in HF patients

Dr. McMurray noted that this study emphasizes the importance of pneumonia vaccination for patients with HF. “Given that we have so few treatments to offer patients with HFpEF, this makes the potential value of vaccination in these patients all the greater,” he said.

The COVID-19 pandemic, Dr. McMurray said, is a “good reminder of the dangers of a respiratory infection and the importance of vaccination in these patients. COVID-19 has interesting parallels in being a systemic disease and one with postacute, persisting effects.”

The persistent risk for adverse cardiovascular events 3 months and later after pneumonia is a novel finding of the study, wrote Donna Mancini, MD, and Gregory Gibson, MD, in an invited commentary (J Am Coll Cardiol. 2021;77:1974-6). Both are with the Icahn School of Medicine at Mt. Sinai in New York. The post hoc study also “serves as an important reminder” of pneumonia risk in patients with HF, especially during the pandemic, they wrote.

“Although vaccination alone appears unlikely to be a panacea, it is a readily accessible tool for mitigating disease severity and improving outcomes,” Dr. Mancini and Dr. Gibson wrote. “After all, an ounce of prevention is worth a pound of cure.”

Novartis provided funding for the PARADIGM-HF and PARAGON-HF trials, and Dr. McMurray and coauthors disclosed financial relationships with Novartis. Dr. Mancini and Dr. Gibson have no relevant financial relationships to disclose.

Patients with heart failure get pneumonia at a rate almost three times greater than expected and, once they do get pneumonia, have about a fourfold greater risk of death, investigators for a retrospective analysis of 13,000 patients from two landmark randomized HF trials have found.

Catherine Hackett/MDedge News

The investigators also found that HF patients with preserved ejection fraction (HFpEF) are at the highest risk of developing pneumonia. The findings underscore the importance of patients with HF getting a pneumonia vaccination, they found.

The analysis showed that 6.3% of patients in the PARADIGM-HF trial and 10.6% of those in the PARAGON-HF trial developed pneumonia, reported the study authors, led by John J.V. McMurray, MD, of the British Heart Foundation Cardiovascular Research Center at the University of Glasgow in Scotland (J Am Coll Cardiol. 2021;77:1961-73).

“The main reason for doing this study was the fact that many heart failure patients are not vaccinated, as they should be, against pneumonia – both pneumococcus and influenza vaccination,” Dr. McMurray said in an interview. “We wanted to document the frequency and consequences of pneumonia in patients with heart failure to help highlight this deficiency in care.”

Dr. McMurray said he believes this is the first study to document the incidence of pneumonia and pneumonia-related outcomes according to the two major ejection fraction phenotypes.
 

PARADIGM-HF and PARAGON-HF

The post hoc analysis consisted of 8,399 patients with HF with reduced ejection fraction (HFrEF) in PARADIGM-HF (Eur J Heart Fail. 2013 Sep;15[9]:1062-73) and 4,796 patients with HFpEF in PARAGON-HF (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The analysis focused on the 528 and 510 patients in each study, respectively, who developed pneumonia. Those rates translated to an incidence rate of 29 per 1,000 patient-years (95% confidence interval, 27-31) in PARADIGM-HF and 39 per 1,000 patient-years (95% CI, 36-42) in PARAGON-HF.

After pneumonia, the risk of death in patients increased substantially. In PARADIGM-HF, the adjusted hazard ratio for the risk of death from any cause after pneumonia was 4.34 (95% CI, 3.73-5.05). In PARAGON-HF, it was 3.76 (95% CI, 3.09-4.58). HF patients who contracted pneumonia also tended to have HF longer than their counterparts who didn’t develop pneumonia, but the frequency of previous hospitalization for HF didn’t vary between the pneumonia and no-pneumonia groups.

Patients who developed pneumonia tended to be older (average age of 66.9 years vs. 64.6 years, P < .001) and male (83.9% vs. 77.8%, P < .001). The mean age of patients in PARADIGM-HF was almost a decade younger than those in PARAGON-HF, 64 vs. 73 years.

Pneumonia patients also had worse Kansas City Cardiomyopathy Questionnaire scores (76 vs. 80 on average), but no difference in New York Heart Association functional class. “In general, patients who developed pneumonia had more symptoms and signs and HF than those who did not develop pneumonia,” Dr. McMurray and colleagues wrote.

Pneumonia patients also had higher rates of chronic obstructive pulmonary disease (26% vs. 12%), diabetes (43% vs. 34%), and atrial fibrillation (46% vs. 36%).

Another reason for conducting the study, Dr. McMurray said, “was the prior findings in patients with coronary disease and acute myocardial infarction that the risk associated with an episode of pneumonia [e.g., in subsequent vascular events and deaths] persisted long after the acute event. We wanted to see if this was also the case for heart failure, and indeed it was.”

For example, the adjusted HR for cardiovascular death or hospitalization in the first month following an episode of pneumonia was 9.48 (range of 6.85-13.12, P < .001), leveling off to 1.59 after 3 months or more.
 

Vaccination crucial in HF patients

Dr. McMurray noted that this study emphasizes the importance of pneumonia vaccination for patients with HF. “Given that we have so few treatments to offer patients with HFpEF, this makes the potential value of vaccination in these patients all the greater,” he said.

The COVID-19 pandemic, Dr. McMurray said, is a “good reminder of the dangers of a respiratory infection and the importance of vaccination in these patients. COVID-19 has interesting parallels in being a systemic disease and one with postacute, persisting effects.”

The persistent risk for adverse cardiovascular events 3 months and later after pneumonia is a novel finding of the study, wrote Donna Mancini, MD, and Gregory Gibson, MD, in an invited commentary (J Am Coll Cardiol. 2021;77:1974-6). Both are with the Icahn School of Medicine at Mt. Sinai in New York. The post hoc study also “serves as an important reminder” of pneumonia risk in patients with HF, especially during the pandemic, they wrote.

“Although vaccination alone appears unlikely to be a panacea, it is a readily accessible tool for mitigating disease severity and improving outcomes,” Dr. Mancini and Dr. Gibson wrote. “After all, an ounce of prevention is worth a pound of cure.”

Novartis provided funding for the PARADIGM-HF and PARAGON-HF trials, and Dr. McMurray and coauthors disclosed financial relationships with Novartis. Dr. Mancini and Dr. Gibson have no relevant financial relationships to disclose.

Chronic lymphocytic leukemia (CLL) patients present significant problems with regard to COVID-19 disease, according to a literature review by Yousef Roosta, MD, of Urmia (Iran) University of Medical Sciences, and colleagues.

Diagnostic interaction between CLL and COVID-19 provides a major challenge. CLL patients have a lower rate of anti–SARS-CoV-2 IgG development, and evidence shows worse therapeutic outcomes in these patients, according to study published in Leukemia Research Reports.

The researchers assessed 20 retrieved articles, 11 of which examined patients with CLL and with concomitant COVID-19; and 9 articles were designed as prospective or retrospective case series of such patients. The studies were assessed qualitatively by the QUADAS-2 tool.
 

Troubling results

Although the overall prevalence of CLL and COVID-19 concurrence was low, at 0.6% (95% confidence interval 0.5%-0.7%) according to the meta-analysis, the results showed some special challenges in the diagnosis and care of these patients.

Diagnostic difficulties are a unique problem. Lymphopenia is common in patients with COVID-19, while lymphocytosis may be considered a transient or even rare finding. The interplay between the two diseases is sometimes very misleading for specialists, and in patients with lymphocytosis, the diagnosis of CLL may be completely ignored, according to the researchers. They added that when performing a diagnostic approach for concurrent COVID-19 and CLL, due to differences in the amount and type of immune response, “relying on serological testing, and especially the evaluation of the anti–SARS-CoV-2 IgG levels may not be beneficial,” they indicated.

In addition, studies showed unacceptable therapeutic outcome in patients with concurrent CLL and COVID-19, with mortality ranging from 33% to 41.7%, showing a need to revise current treatment protocols, according to the authors. In one study, 85.7% of surviving patients showed a considerable decrease in functional class and significant fatigue, with such a poor prognosis occurring more commonly in the elderly.

With regard to treatment, “it is quite obvious that despite the use of current standard protocols, the prognosis of these patients will be much worse than the prognosis of CLL patients with no evidence of COVID-19. Even in the first-line treatment protocol for these patients, there is no agreement in combination therapy with selected CLL drugs along with management protocols of COVID-19 patients,” the researchers stated.

“[The] different hematological behaviors of two diseases might mimic the detection of COVID-19 in the CLL state and vise versa. Also, due to the low level of immune response against SARS-CoV-2 in CLL patients, both scheduled immunological-based diagnosis and treatment may fail,” the researchers added.

The authors reported that they had no disclosures.

[email protected]

Chronic lymphocytic leukemia (CLL) patients present significant problems with regard to COVID-19 disease, according to a literature review by Yousef Roosta, MD, of Urmia (Iran) University of Medical Sciences, and colleagues.

Diagnostic interaction between CLL and COVID-19 provides a major challenge. CLL patients have a lower rate of anti–SARS-CoV-2 IgG development, and evidence shows worse therapeutic outcomes in these patients, according to study published in Leukemia Research Reports.

The researchers assessed 20 retrieved articles, 11 of which examined patients with CLL and with concomitant COVID-19; and 9 articles were designed as prospective or retrospective case series of such patients. The studies were assessed qualitatively by the QUADAS-2 tool.
 

Troubling results

Although the overall prevalence of CLL and COVID-19 concurrence was low, at 0.6% (95% confidence interval 0.5%-0.7%) according to the meta-analysis, the results showed some special challenges in the diagnosis and care of these patients.

Diagnostic difficulties are a unique problem. Lymphopenia is common in patients with COVID-19, while lymphocytosis may be considered a transient or even rare finding. The interplay between the two diseases is sometimes very misleading for specialists, and in patients with lymphocytosis, the diagnosis of CLL may be completely ignored, according to the researchers. They added that when performing a diagnostic approach for concurrent COVID-19 and CLL, due to differences in the amount and type of immune response, “relying on serological testing, and especially the evaluation of the anti–SARS-CoV-2 IgG levels may not be beneficial,” they indicated.

In addition, studies showed unacceptable therapeutic outcome in patients with concurrent CLL and COVID-19, with mortality ranging from 33% to 41.7%, showing a need to revise current treatment protocols, according to the authors. In one study, 85.7% of surviving patients showed a considerable decrease in functional class and significant fatigue, with such a poor prognosis occurring more commonly in the elderly.

With regard to treatment, “it is quite obvious that despite the use of current standard protocols, the prognosis of these patients will be much worse than the prognosis of CLL patients with no evidence of COVID-19. Even in the first-line treatment protocol for these patients, there is no agreement in combination therapy with selected CLL drugs along with management protocols of COVID-19 patients,” the researchers stated.

“[The] different hematological behaviors of two diseases might mimic the detection of COVID-19 in the CLL state and vise versa. Also, due to the low level of immune response against SARS-CoV-2 in CLL patients, both scheduled immunological-based diagnosis and treatment may fail,” the researchers added.

The authors reported that they had no disclosures.

[email protected]

Chronic lymphocytic leukemia (CLL) patients present significant problems with regard to COVID-19 disease, according to a literature review by Yousef Roosta, MD, of Urmia (Iran) University of Medical Sciences, and colleagues.

Diagnostic interaction between CLL and COVID-19 provides a major challenge. CLL patients have a lower rate of anti–SARS-CoV-2 IgG development, and evidence shows worse therapeutic outcomes in these patients, according to study published in Leukemia Research Reports.

The researchers assessed 20 retrieved articles, 11 of which examined patients with CLL and with concomitant COVID-19; and 9 articles were designed as prospective or retrospective case series of such patients. The studies were assessed qualitatively by the QUADAS-2 tool.
 

Troubling results

Although the overall prevalence of CLL and COVID-19 concurrence was low, at 0.6% (95% confidence interval 0.5%-0.7%) according to the meta-analysis, the results showed some special challenges in the diagnosis and care of these patients.

Diagnostic difficulties are a unique problem. Lymphopenia is common in patients with COVID-19, while lymphocytosis may be considered a transient or even rare finding. The interplay between the two diseases is sometimes very misleading for specialists, and in patients with lymphocytosis, the diagnosis of CLL may be completely ignored, according to the researchers. They added that when performing a diagnostic approach for concurrent COVID-19 and CLL, due to differences in the amount and type of immune response, “relying on serological testing, and especially the evaluation of the anti–SARS-CoV-2 IgG levels may not be beneficial,” they indicated.

In addition, studies showed unacceptable therapeutic outcome in patients with concurrent CLL and COVID-19, with mortality ranging from 33% to 41.7%, showing a need to revise current treatment protocols, according to the authors. In one study, 85.7% of surviving patients showed a considerable decrease in functional class and significant fatigue, with such a poor prognosis occurring more commonly in the elderly.

With regard to treatment, “it is quite obvious that despite the use of current standard protocols, the prognosis of these patients will be much worse than the prognosis of CLL patients with no evidence of COVID-19. Even in the first-line treatment protocol for these patients, there is no agreement in combination therapy with selected CLL drugs along with management protocols of COVID-19 patients,” the researchers stated.

“[The] different hematological behaviors of two diseases might mimic the detection of COVID-19 in the CLL state and vise versa. Also, due to the low level of immune response against SARS-CoV-2 in CLL patients, both scheduled immunological-based diagnosis and treatment may fail,” the researchers added.

The authors reported that they had no disclosures.

[email protected]

Low-fat diets appear to decrease testosterone levels in men, but further randomized, controlled trials are needed to confirm this effect, the authors of a meta-analysis of six small intervention studies concluded.

A total of 206 healthy men with normal testosterone received a high-fat diet followed by a low-fat diet (or vice versa), and their mean total testosterone levels were 10%-15% lower (but still in the normal range) during the low-fat diet.

The study by registered nutritionist Joseph Whittaker, MSc, University of Worcester (England), and statistician Kexin Wu, MSc, University of Warwick, Coventry, England, was published online in the Journal of Steroid Biochemistry and Molecular Biology.

“I think our results are consistent and fairly strong, but they are not strong enough to give blanket recommendations,” Mr. Whittaker said in an interview.

However, “if somebody has low testosterone, particularly borderline, they could try increasing their fat intake, maybe on a Mediterranean diet,” he said, and see if that works to increase their testosterone by 60 ng/dL, the weighted mean difference in total testosterone levels between the low-fat versus high-fat diet interventions in this meta-analysis.

“A Mediterranean diet is a good way to increase ‘healthy fats,’ mono- and polyunsaturated fatty acids, which will likely decrease cardiovascular disease risk, and boost testosterone at the same time,” Mr. Whittaker noted.

Olive oil has been shown to boost testosterone more than butter, and it also reduces CVD, he continued. Nuts are high in “healthy fats” and consistently decrease CVD and mortality and may boost testosterone. Other sources of “good fat” in a healthy diet include avocado, and red meat and poultry in moderation.

“It is controversial, but our results also indicate that foods with saturated fatty acids may boost testosterone,” he added, noting however that such foods are also associated with an increase in cholesterol.
 

Is waning testosterone explained by leaner diet?

Men need healthy testosterone levels for good physical performance, mental health, and sexual health, and low levels are associated with a higher risk of heart disease, diabetes, and Alzheimer’s disease, according to a statement about this research issued by the University of Worcester.

Although testosterone levels do decline with advancing age, there has also been an additional age-independent and persistent decline in testosterone levels that began roughly after nutrition guidelines began recommending a lower-fat diet in 1965.

Fat consumption dropped from 45% of the diet in 1965 to 35% of the diet in 1991, and stayed around that lower level through to 2011.

However, it is not clear if this decrease in dietary fat intake might explain part of the concurrent decline in men’s testosterone levels.

Mr. Whittaker and Mr. Wu conducted a systematic literature review and identified six crossover intervention studies that compared testosterone levels during low-fat versus high-fat diets – Dorgan 1996, Wang 2005, Hamalainen 1984, Hill 1980, Reed 1987, and Hill 1979 – and then they combined these studies in a meta-analysis.

Five studies each enrolled 6-43 healthy men from North America, the United Kingdom, and Scandinavia, and the sixth study (Hill 1980) enrolled 34 healthy men from North America and 39 farm laborers from South Africa.

Overall, on average, the men were aged 34-54 years and slightly overweight (a mean body mass index of roughly 27 kg/m²) with normal testosterone (i.e., >300 ng/dL, based on the 2018 American Urological Association guidelines criteria).

Most men received a high-fat diet (40% of calories from fat) first, followed by a low-fat diet (on average 20% of calories from fat; range, 7%-25%), but the subgroup of men from South Africa received the low-fat diet first.

To put this into context, U.K. guidelines recommend a fat intake of less than 35% of daily calories, and U.S. guidelines recommend a fat intake of 20%-35% of daily calories.

The low-and high-fat interventions ranged from 2 to 10 weeks.  
 

Lowest testosterone levels with low-fat vegetarian diets

Overall, on average, the men’s total testosterone was 475 mg/dL when they were consuming a low-fat diet and 532 mg/dL when they were consuming a high-fat diet.

However, the South African men had higher testosterone levels when they consumed a low-fat diet. This suggests that “men with European ancestry may experience a greater decrease in testosterone in response to a low-fat diet,” the researchers wrote.

The decrease in total testosterone in the low-fat versus high-fat diet was largest (26%) in the two studies of men who consumed a vegetarian diet (Hill 1979 and Hill 1980). These diets may have been low in zinc, since a marginal zinc deficiency has been shown to decrease total testosterone, Mr. Whittaker and Mr. Wu speculated.

The meta-analysis also showed that levels of free testosterone, urinary testosterone, and dihydrotestosterone declined during the low-fat diet, whereas levels of luteinizing hormone or sex hormone binding globulin were similar with both diets.
 

Men with low testosterone and overweight, obesity

What nutritional advice should practitioners give to men who have low testosterone and overweight/obesity?

“If you are very overweight, losing weight is going to dramatically improve your testosterone,” Mr. Whittaker said.

However, proponents of various diets are often in stark disagreement about the merits of a low-fat versus low-carbohydrate diet to lose weight.

“In general,” he continued, “the literature shows low-carb (high-fat) diets are better for weight loss [although many will disagree with that statement].”

Although nutrition guidelines have stressed the importance of limiting fat intake, fat in the diet is also associated with lower triglyceride levels and blood pressure and higher HDL cholesterol levels, and now in this study, higher testosterone levels.
 

More research needed

The researchers acknowledge study limitations: The meta-analysis included just a few small studies with heterogeneous designs and findings, and there was possible bias from confounding variables.

“Ideally, we would like to see a few more studies to confirm our results,” Mr. Whittaker said in the statement. “However, these studies may never come; normally researchers want to find new results, not replicate old ones. In the meantime, men with low testosterone would be wise to avoid low-fat diets.”

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors disclosed no relevant financial relationships.

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

Low-fat diets appear to decrease testosterone levels in men, but further randomized, controlled trials are needed to confirm this effect, the authors of a meta-analysis of six small intervention studies concluded.

A total of 206 healthy men with normal testosterone received a high-fat diet followed by a low-fat diet (or vice versa), and their mean total testosterone levels were 10%-15% lower (but still in the normal range) during the low-fat diet.

The study by registered nutritionist Joseph Whittaker, MSc, University of Worcester (England), and statistician Kexin Wu, MSc, University of Warwick, Coventry, England, was published online in the Journal of Steroid Biochemistry and Molecular Biology.

“I think our results are consistent and fairly strong, but they are not strong enough to give blanket recommendations,” Mr. Whittaker said in an interview.

However, “if somebody has low testosterone, particularly borderline, they could try increasing their fat intake, maybe on a Mediterranean diet,” he said, and see if that works to increase their testosterone by 60 ng/dL, the weighted mean difference in total testosterone levels between the low-fat versus high-fat diet interventions in this meta-analysis.

“A Mediterranean diet is a good way to increase ‘healthy fats,’ mono- and polyunsaturated fatty acids, which will likely decrease cardiovascular disease risk, and boost testosterone at the same time,” Mr. Whittaker noted.

Olive oil has been shown to boost testosterone more than butter, and it also reduces CVD, he continued. Nuts are high in “healthy fats” and consistently decrease CVD and mortality and may boost testosterone. Other sources of “good fat” in a healthy diet include avocado, and red meat and poultry in moderation.

“It is controversial, but our results also indicate that foods with saturated fatty acids may boost testosterone,” he added, noting however that such foods are also associated with an increase in cholesterol.
 

Is waning testosterone explained by leaner diet?

Men need healthy testosterone levels for good physical performance, mental health, and sexual health, and low levels are associated with a higher risk of heart disease, diabetes, and Alzheimer’s disease, according to a statement about this research issued by the University of Worcester.

Although testosterone levels do decline with advancing age, there has also been an additional age-independent and persistent decline in testosterone levels that began roughly after nutrition guidelines began recommending a lower-fat diet in 1965.

Fat consumption dropped from 45% of the diet in 1965 to 35% of the diet in 1991, and stayed around that lower level through to 2011.

However, it is not clear if this decrease in dietary fat intake might explain part of the concurrent decline in men’s testosterone levels.

Mr. Whittaker and Mr. Wu conducted a systematic literature review and identified six crossover intervention studies that compared testosterone levels during low-fat versus high-fat diets – Dorgan 1996, Wang 2005, Hamalainen 1984, Hill 1980, Reed 1987, and Hill 1979 – and then they combined these studies in a meta-analysis.

Five studies each enrolled 6-43 healthy men from North America, the United Kingdom, and Scandinavia, and the sixth study (Hill 1980) enrolled 34 healthy men from North America and 39 farm laborers from South Africa.

Overall, on average, the men were aged 34-54 years and slightly overweight (a mean body mass index of roughly 27 kg/m²) with normal testosterone (i.e., >300 ng/dL, based on the 2018 American Urological Association guidelines criteria).

Most men received a high-fat diet (40% of calories from fat) first, followed by a low-fat diet (on average 20% of calories from fat; range, 7%-25%), but the subgroup of men from South Africa received the low-fat diet first.

To put this into context, U.K. guidelines recommend a fat intake of less than 35% of daily calories, and U.S. guidelines recommend a fat intake of 20%-35% of daily calories.

The low-and high-fat interventions ranged from 2 to 10 weeks.  
 

Lowest testosterone levels with low-fat vegetarian diets

Overall, on average, the men’s total testosterone was 475 mg/dL when they were consuming a low-fat diet and 532 mg/dL when they were consuming a high-fat diet.

However, the South African men had higher testosterone levels when they consumed a low-fat diet. This suggests that “men with European ancestry may experience a greater decrease in testosterone in response to a low-fat diet,” the researchers wrote.

The decrease in total testosterone in the low-fat versus high-fat diet was largest (26%) in the two studies of men who consumed a vegetarian diet (Hill 1979 and Hill 1980). These diets may have been low in zinc, since a marginal zinc deficiency has been shown to decrease total testosterone, Mr. Whittaker and Mr. Wu speculated.

The meta-analysis also showed that levels of free testosterone, urinary testosterone, and dihydrotestosterone declined during the low-fat diet, whereas levels of luteinizing hormone or sex hormone binding globulin were similar with both diets.
 

Men with low testosterone and overweight, obesity

What nutritional advice should practitioners give to men who have low testosterone and overweight/obesity?

“If you are very overweight, losing weight is going to dramatically improve your testosterone,” Mr. Whittaker said.

However, proponents of various diets are often in stark disagreement about the merits of a low-fat versus low-carbohydrate diet to lose weight.

“In general,” he continued, “the literature shows low-carb (high-fat) diets are better for weight loss [although many will disagree with that statement].”

Although nutrition guidelines have stressed the importance of limiting fat intake, fat in the diet is also associated with lower triglyceride levels and blood pressure and higher HDL cholesterol levels, and now in this study, higher testosterone levels.
 

More research needed

The researchers acknowledge study limitations: The meta-analysis included just a few small studies with heterogeneous designs and findings, and there was possible bias from confounding variables.

“Ideally, we would like to see a few more studies to confirm our results,” Mr. Whittaker said in the statement. “However, these studies may never come; normally researchers want to find new results, not replicate old ones. In the meantime, men with low testosterone would be wise to avoid low-fat diets.”

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors disclosed no relevant financial relationships.

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

Low-fat diets appear to decrease testosterone levels in men, but further randomized, controlled trials are needed to confirm this effect, the authors of a meta-analysis of six small intervention studies concluded.

A total of 206 healthy men with normal testosterone received a high-fat diet followed by a low-fat diet (or vice versa), and their mean total testosterone levels were 10%-15% lower (but still in the normal range) during the low-fat diet.

The study by registered nutritionist Joseph Whittaker, MSc, University of Worcester (England), and statistician Kexin Wu, MSc, University of Warwick, Coventry, England, was published online in the Journal of Steroid Biochemistry and Molecular Biology.

“I think our results are consistent and fairly strong, but they are not strong enough to give blanket recommendations,” Mr. Whittaker said in an interview.

However, “if somebody has low testosterone, particularly borderline, they could try increasing their fat intake, maybe on a Mediterranean diet,” he said, and see if that works to increase their testosterone by 60 ng/dL, the weighted mean difference in total testosterone levels between the low-fat versus high-fat diet interventions in this meta-analysis.

“A Mediterranean diet is a good way to increase ‘healthy fats,’ mono- and polyunsaturated fatty acids, which will likely decrease cardiovascular disease risk, and boost testosterone at the same time,” Mr. Whittaker noted.

Olive oil has been shown to boost testosterone more than butter, and it also reduces CVD, he continued. Nuts are high in “healthy fats” and consistently decrease CVD and mortality and may boost testosterone. Other sources of “good fat” in a healthy diet include avocado, and red meat and poultry in moderation.

“It is controversial, but our results also indicate that foods with saturated fatty acids may boost testosterone,” he added, noting however that such foods are also associated with an increase in cholesterol.
 

Is waning testosterone explained by leaner diet?

Men need healthy testosterone levels for good physical performance, mental health, and sexual health, and low levels are associated with a higher risk of heart disease, diabetes, and Alzheimer’s disease, according to a statement about this research issued by the University of Worcester.

Although testosterone levels do decline with advancing age, there has also been an additional age-independent and persistent decline in testosterone levels that began roughly after nutrition guidelines began recommending a lower-fat diet in 1965.

Fat consumption dropped from 45% of the diet in 1965 to 35% of the diet in 1991, and stayed around that lower level through to 2011.

However, it is not clear if this decrease in dietary fat intake might explain part of the concurrent decline in men’s testosterone levels.

Mr. Whittaker and Mr. Wu conducted a systematic literature review and identified six crossover intervention studies that compared testosterone levels during low-fat versus high-fat diets – Dorgan 1996, Wang 2005, Hamalainen 1984, Hill 1980, Reed 1987, and Hill 1979 – and then they combined these studies in a meta-analysis.

Five studies each enrolled 6-43 healthy men from North America, the United Kingdom, and Scandinavia, and the sixth study (Hill 1980) enrolled 34 healthy men from North America and 39 farm laborers from South Africa.

Overall, on average, the men were aged 34-54 years and slightly overweight (a mean body mass index of roughly 27 kg/m²) with normal testosterone (i.e., >300 ng/dL, based on the 2018 American Urological Association guidelines criteria).

Most men received a high-fat diet (40% of calories from fat) first, followed by a low-fat diet (on average 20% of calories from fat; range, 7%-25%), but the subgroup of men from South Africa received the low-fat diet first.

To put this into context, U.K. guidelines recommend a fat intake of less than 35% of daily calories, and U.S. guidelines recommend a fat intake of 20%-35% of daily calories.

The low-and high-fat interventions ranged from 2 to 10 weeks.  
 

Lowest testosterone levels with low-fat vegetarian diets

Overall, on average, the men’s total testosterone was 475 mg/dL when they were consuming a low-fat diet and 532 mg/dL when they were consuming a high-fat diet.

However, the South African men had higher testosterone levels when they consumed a low-fat diet. This suggests that “men with European ancestry may experience a greater decrease in testosterone in response to a low-fat diet,” the researchers wrote.

The decrease in total testosterone in the low-fat versus high-fat diet was largest (26%) in the two studies of men who consumed a vegetarian diet (Hill 1979 and Hill 1980). These diets may have been low in zinc, since a marginal zinc deficiency has been shown to decrease total testosterone, Mr. Whittaker and Mr. Wu speculated.

The meta-analysis also showed that levels of free testosterone, urinary testosterone, and dihydrotestosterone declined during the low-fat diet, whereas levels of luteinizing hormone or sex hormone binding globulin were similar with both diets.
 

Men with low testosterone and overweight, obesity

What nutritional advice should practitioners give to men who have low testosterone and overweight/obesity?

“If you are very overweight, losing weight is going to dramatically improve your testosterone,” Mr. Whittaker said.

However, proponents of various diets are often in stark disagreement about the merits of a low-fat versus low-carbohydrate diet to lose weight.

“In general,” he continued, “the literature shows low-carb (high-fat) diets are better for weight loss [although many will disagree with that statement].”

Although nutrition guidelines have stressed the importance of limiting fat intake, fat in the diet is also associated with lower triglyceride levels and blood pressure and higher HDL cholesterol levels, and now in this study, higher testosterone levels.
 

More research needed

The researchers acknowledge study limitations: The meta-analysis included just a few small studies with heterogeneous designs and findings, and there was possible bias from confounding variables.

“Ideally, we would like to see a few more studies to confirm our results,” Mr. Whittaker said in the statement. “However, these studies may never come; normally researchers want to find new results, not replicate old ones. In the meantime, men with low testosterone would be wise to avoid low-fat diets.”

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors disclosed no relevant financial relationships.

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

The U.S. Food and Drug Administration has approved the immunotherapy nivolumab (Opdivo, Bristol-Myers Squibb) in conjunction with certain chemotherapies for the frontline treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

This is the first immunotherapy approved for the frontline treatment of gastric cancers, the agency says in a press release.

The approval comes after nivolumab received Priority Review and Orphan Drug designations for this indication. There are approximately 28,000 new diagnoses of gastric cancer annually in the United States, and overall survival is generally poor with currently available therapy, points out the FDA.

“Today’s approval is the first treatment in more than a decade to show a survival benefit for patients with advanced or metastatic gastric cancer who are being treated for the first time,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, states in an FDA press release.

Efficacy in the gastric cancer setting was demonstrated in the randomized, phase 3, open-label CheckMate 649 study of 1,518 untreated patients. Median survival was 13.8 months among those treated with nivolumab, compared with 11.6 months with chemotherapy alone (hazard ratio, 0.80; P = .0002).

Common side effects experienced by patients in the nivolumab group included peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain.

Nivolumab is also approved for numerous other cancers. Other known adverse effects include immune-mediated inflammation of the lungs, colon, liver, endocrine glands, and kidneys.

“Patients should tell their health care providers if they have immune system problems, lung or breathing problems, liver problems, have had an organ transplant, or are pregnant or plan to become pregnant before starting treatment,” the FDA states.

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

The U.S. Food and Drug Administration has approved the immunotherapy nivolumab (Opdivo, Bristol-Myers Squibb) in conjunction with certain chemotherapies for the frontline treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

This is the first immunotherapy approved for the frontline treatment of gastric cancers, the agency says in a press release.

The approval comes after nivolumab received Priority Review and Orphan Drug designations for this indication. There are approximately 28,000 new diagnoses of gastric cancer annually in the United States, and overall survival is generally poor with currently available therapy, points out the FDA.

“Today’s approval is the first treatment in more than a decade to show a survival benefit for patients with advanced or metastatic gastric cancer who are being treated for the first time,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, states in an FDA press release.

Efficacy in the gastric cancer setting was demonstrated in the randomized, phase 3, open-label CheckMate 649 study of 1,518 untreated patients. Median survival was 13.8 months among those treated with nivolumab, compared with 11.6 months with chemotherapy alone (hazard ratio, 0.80; P = .0002).

Common side effects experienced by patients in the nivolumab group included peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain.

Nivolumab is also approved for numerous other cancers. Other known adverse effects include immune-mediated inflammation of the lungs, colon, liver, endocrine glands, and kidneys.

“Patients should tell their health care providers if they have immune system problems, lung or breathing problems, liver problems, have had an organ transplant, or are pregnant or plan to become pregnant before starting treatment,” the FDA states.

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

The U.S. Food and Drug Administration has approved the immunotherapy nivolumab (Opdivo, Bristol-Myers Squibb) in conjunction with certain chemotherapies for the frontline treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

This is the first immunotherapy approved for the frontline treatment of gastric cancers, the agency says in a press release.

The approval comes after nivolumab received Priority Review and Orphan Drug designations for this indication. There are approximately 28,000 new diagnoses of gastric cancer annually in the United States, and overall survival is generally poor with currently available therapy, points out the FDA.

“Today’s approval is the first treatment in more than a decade to show a survival benefit for patients with advanced or metastatic gastric cancer who are being treated for the first time,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, states in an FDA press release.

Efficacy in the gastric cancer setting was demonstrated in the randomized, phase 3, open-label CheckMate 649 study of 1,518 untreated patients. Median survival was 13.8 months among those treated with nivolumab, compared with 11.6 months with chemotherapy alone (hazard ratio, 0.80; P = .0002).

Common side effects experienced by patients in the nivolumab group included peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain.

Nivolumab is also approved for numerous other cancers. Other known adverse effects include immune-mediated inflammation of the lungs, colon, liver, endocrine glands, and kidneys.

“Patients should tell their health care providers if they have immune system problems, lung or breathing problems, liver problems, have had an organ transplant, or are pregnant or plan to become pregnant before starting treatment,” the FDA states.

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

Progress is being made in the quest for an oral treatment for sickle cell disease. In preclinical trials, a new drug has shown the ability to induce blood cells to produce fetal hemoglobin at levels predicted to prevent sickling. The new small-molecule drug could be formulated into a convenient daily oral dosage, according to researchers who presented their results at the spring meeting of the American Chemical Society, which was held virtually.

The new drug candidate, designated FTX-6058 by Fulcrum Therapeutics, was developed using a proprietary small-molecule probe and CRISPR guide RNA libraries to screen “a disease-relevant cell model that allowed us to pinpoint a treatment target,” said Ivan V. Efremov, PhD, senior director, head of medicinal chemistry at the company, who presented the research.

Even though sickle cell patients carry genes leading to defective adult hemoglobin, they still carry stem cells in their bone marrow with the potential to produce fetal hemoglobin. FTX-6058 attaches to a protein inside these bone marrow stem cells destined to become mature red blood cells and reinstates their fetal hemoglobin expression, according to Dr. Efremov.

“What is really key is FTX-6058 upregulates fetal hemoglobin across all red blood cells, a pancellular distribution,” he explained, adding that if “some red blood cells did not express this, they could still sickle and cause disease symptoms.”

The premise behind the development of the drug evolved from the example of patients with sickle cell genes who also have a mutation that causes fetal hemoglobin production. The presence of fetal hemoglobin provides significant benefits to patients with sickle cell disease. At around 5%-10% levels of fetal hemoglobin expression, mortality is reduced. By 10%-25% levels of fetal hemoglobin, recurring events including vaso-occlusive crises, acute chest syndrome, and hospitalization are reduced. When fetal hemoglobin levels reaches around 25%-30%, enough red blood cell function is restored so that these patients become asymptomatic, Dr. Efremov said.

FTX-6058 was designed to mimic this effect.

FTX-6058 inhibits the action of the polycomb repressive complex 2 (PRC2) via binding to the EED subunit. PRC2 acts as a histone methyltransferase to control gene expression. Inhibition of PRC2 leads to significant fetal hemoglobin protein expression in both cell and mouse models. Other such inhibitors are under study for the suppression of cancer progression.

Preclinical experiments comparing FTX-6058 with the fetal hemoglobin booster, hydroxyurea, approved in the 1990s, showed the new drug candidate outperforms the current treatment, Christopher Moxham, PhD, chief scientific officer of Fulcrum Therapeutics, said in a company press release. The company began a phase 1 safety trial in healthy adult volunteers last year after preclinical experiments with FTX-6058 in human-derived cell assay systems and mouse models also showed an increase in fetal hemoglobin to meet the 25%-30% asymptomatic symptom threshold level.
 

Ongoing studies

The researchers plan to launch phase 2 clinical trial enrolling patients with sickle cell disease by end of 2021. In addition, further characterization of the therapeutic molecule is continuing, using genomics and additional cell assay systems to expand details FTX-6058’s mode of action.

The company also is looking to explore the use of FTX-6058 in patients with beta-thalassemia to supplement their reduced hemoglobin production.

The pharmacologic profile of FTX-6058 indicates that the drug has the potential to be administered as a once-a-day oral formulation, Dr. Efremov stated. Both the preclinical PK [pharmacokinetic] data and “the emerging PK from the human clinical study supports once-a-day oral administration, which obviously offers significant convenience to patients,” he added.

Fulcrum Therapeutics is funding the studies.

[email protected]

Progress is being made in the quest for an oral treatment for sickle cell disease. In preclinical trials, a new drug has shown the ability to induce blood cells to produce fetal hemoglobin at levels predicted to prevent sickling. The new small-molecule drug could be formulated into a convenient daily oral dosage, according to researchers who presented their results at the spring meeting of the American Chemical Society, which was held virtually.

The new drug candidate, designated FTX-6058 by Fulcrum Therapeutics, was developed using a proprietary small-molecule probe and CRISPR guide RNA libraries to screen “a disease-relevant cell model that allowed us to pinpoint a treatment target,” said Ivan V. Efremov, PhD, senior director, head of medicinal chemistry at the company, who presented the research.

Even though sickle cell patients carry genes leading to defective adult hemoglobin, they still carry stem cells in their bone marrow with the potential to produce fetal hemoglobin. FTX-6058 attaches to a protein inside these bone marrow stem cells destined to become mature red blood cells and reinstates their fetal hemoglobin expression, according to Dr. Efremov.

“What is really key is FTX-6058 upregulates fetal hemoglobin across all red blood cells, a pancellular distribution,” he explained, adding that if “some red blood cells did not express this, they could still sickle and cause disease symptoms.”

The premise behind the development of the drug evolved from the example of patients with sickle cell genes who also have a mutation that causes fetal hemoglobin production. The presence of fetal hemoglobin provides significant benefits to patients with sickle cell disease. At around 5%-10% levels of fetal hemoglobin expression, mortality is reduced. By 10%-25% levels of fetal hemoglobin, recurring events including vaso-occlusive crises, acute chest syndrome, and hospitalization are reduced. When fetal hemoglobin levels reaches around 25%-30%, enough red blood cell function is restored so that these patients become asymptomatic, Dr. Efremov said.

FTX-6058 was designed to mimic this effect.

FTX-6058 inhibits the action of the polycomb repressive complex 2 (PRC2) via binding to the EED subunit. PRC2 acts as a histone methyltransferase to control gene expression. Inhibition of PRC2 leads to significant fetal hemoglobin protein expression in both cell and mouse models. Other such inhibitors are under study for the suppression of cancer progression.

Preclinical experiments comparing FTX-6058 with the fetal hemoglobin booster, hydroxyurea, approved in the 1990s, showed the new drug candidate outperforms the current treatment, Christopher Moxham, PhD, chief scientific officer of Fulcrum Therapeutics, said in a company press release. The company began a phase 1 safety trial in healthy adult volunteers last year after preclinical experiments with FTX-6058 in human-derived cell assay systems and mouse models also showed an increase in fetal hemoglobin to meet the 25%-30% asymptomatic symptom threshold level.
 

Ongoing studies

The researchers plan to launch phase 2 clinical trial enrolling patients with sickle cell disease by end of 2021. In addition, further characterization of the therapeutic molecule is continuing, using genomics and additional cell assay systems to expand details FTX-6058’s mode of action.

The company also is looking to explore the use of FTX-6058 in patients with beta-thalassemia to supplement their reduced hemoglobin production.

The pharmacologic profile of FTX-6058 indicates that the drug has the potential to be administered as a once-a-day oral formulation, Dr. Efremov stated. Both the preclinical PK [pharmacokinetic] data and “the emerging PK from the human clinical study supports once-a-day oral administration, which obviously offers significant convenience to patients,” he added.

Fulcrum Therapeutics is funding the studies.

[email protected]

Progress is being made in the quest for an oral treatment for sickle cell disease. In preclinical trials, a new drug has shown the ability to induce blood cells to produce fetal hemoglobin at levels predicted to prevent sickling. The new small-molecule drug could be formulated into a convenient daily oral dosage, according to researchers who presented their results at the spring meeting of the American Chemical Society, which was held virtually.

The new drug candidate, designated FTX-6058 by Fulcrum Therapeutics, was developed using a proprietary small-molecule probe and CRISPR guide RNA libraries to screen “a disease-relevant cell model that allowed us to pinpoint a treatment target,” said Ivan V. Efremov, PhD, senior director, head of medicinal chemistry at the company, who presented the research.

Even though sickle cell patients carry genes leading to defective adult hemoglobin, they still carry stem cells in their bone marrow with the potential to produce fetal hemoglobin. FTX-6058 attaches to a protein inside these bone marrow stem cells destined to become mature red blood cells and reinstates their fetal hemoglobin expression, according to Dr. Efremov.

“What is really key is FTX-6058 upregulates fetal hemoglobin across all red blood cells, a pancellular distribution,” he explained, adding that if “some red blood cells did not express this, they could still sickle and cause disease symptoms.”

The premise behind the development of the drug evolved from the example of patients with sickle cell genes who also have a mutation that causes fetal hemoglobin production. The presence of fetal hemoglobin provides significant benefits to patients with sickle cell disease. At around 5%-10% levels of fetal hemoglobin expression, mortality is reduced. By 10%-25% levels of fetal hemoglobin, recurring events including vaso-occlusive crises, acute chest syndrome, and hospitalization are reduced. When fetal hemoglobin levels reaches around 25%-30%, enough red blood cell function is restored so that these patients become asymptomatic, Dr. Efremov said.

FTX-6058 was designed to mimic this effect.

FTX-6058 inhibits the action of the polycomb repressive complex 2 (PRC2) via binding to the EED subunit. PRC2 acts as a histone methyltransferase to control gene expression. Inhibition of PRC2 leads to significant fetal hemoglobin protein expression in both cell and mouse models. Other such inhibitors are under study for the suppression of cancer progression.

Preclinical experiments comparing FTX-6058 with the fetal hemoglobin booster, hydroxyurea, approved in the 1990s, showed the new drug candidate outperforms the current treatment, Christopher Moxham, PhD, chief scientific officer of Fulcrum Therapeutics, said in a company press release. The company began a phase 1 safety trial in healthy adult volunteers last year after preclinical experiments with FTX-6058 in human-derived cell assay systems and mouse models also showed an increase in fetal hemoglobin to meet the 25%-30% asymptomatic symptom threshold level.
 

Ongoing studies

The researchers plan to launch phase 2 clinical trial enrolling patients with sickle cell disease by end of 2021. In addition, further characterization of the therapeutic molecule is continuing, using genomics and additional cell assay systems to expand details FTX-6058’s mode of action.

The company also is looking to explore the use of FTX-6058 in patients with beta-thalassemia to supplement their reduced hemoglobin production.

The pharmacologic profile of FTX-6058 indicates that the drug has the potential to be administered as a once-a-day oral formulation, Dr. Efremov stated. Both the preclinical PK [pharmacokinetic] data and “the emerging PK from the human clinical study supports once-a-day oral administration, which obviously offers significant convenience to patients,” he added.

Fulcrum Therapeutics is funding the studies.

[email protected]