Among the many losses suffered by millions worldwide during the COVID-19 pandemic, the loss of sleep may be the most widespread, with potentially long-lasting, negative consequences on physical, mental, and emotional health, sleep researchers have found.

Results from multiple studies and surveys conducted during the pandemic show that a majority of subjects report clinically meaningful changes in sleep quality, sleep patterns, and sleep disturbances.

klebercordeiro/Getty Images

Sleeping, more or less

A coauthor of that study, David Gozal, MD, FCCP, a pediatric pulmonologist and sleep medicine specialist at the University of Missouri in Columbia, said that the pandemic has had paradoxical effects on sleeps patterns for many.

“At the beginning, with the initial phases of lockdown for COVID, for most of the people whose jobs were not affected and who did not lose their jobs, [for whom] there was not the anxiety of being jobless and financially strapped, but who now were staying at home, there was actually a benefit. People started reporting getting more sleep and, more importantly, more vivid dreams and things of that nature,” he said in an interview.

“But as the lockdown progressed, we saw progressively and increasingly more people having difficulty falling asleep and staying asleep, using more medicines such as hypnotics to induce sleep, and we saw a 20% increase in the overall consumption of sleeping pills,” he said.

Similar results were seen in a cross-sectional survey of 843 adults in the United Kingdom, which showed that nearly 70% of participants reported a change in sleep patterns, only 45% reported having refreshing sleep, and 46% reported being sleepier during lockdown than before. Two-thirds of the respondents reported that the pandemic affected their mental health, and one-fourth reported increased alcohol consumption during lockdown. Those with suspected COVID-19 infections reported having more nightmares and abnormal sleep rhythms.

It is possible that the effects of COVID-19 infection on sleep may linger long after the infection itself has resolved, results of a cohort study from China suggest. As reported in The Lancet, among 1,655 patients discharged from the Jin Yin-tan hospital in Wuhan, 26% reported sleep disturbances 6 months after acute COVID-19 infection.
 

Self-medicating

Among 5,525 Canadians surveyed from April 3 through June 24, 2020, a large proportion reported the use of pharmacologic sleeps aids, said Tetyana Kendzerska, MD, PhD, assistant professor of medicine in the division of respirology at the University of Ottawa.

“At the time of the survey completion, 27% of participants reported taking sleeping aids (prescribed or [over] the counter); across the entire sample, 8% of respondents reported an increase in the frequency of sleeping medication use during the outbreak compared to before the outbreak,” she said in an interview.

Many people resort to self-medicating with over-the-counter preparations such as melatonin and pain-relief nighttime formulations containing diphenhydramine (Benadryl), a first-generation antihistamine with sedative properties, noted Kannan Ramar, MBBS, MD, a critical care, pulmonary, and sleep medicine specialist at the Mayo Clinic in Rochester, Minn., and current president of the American Academy of Sleep Medicine.

“When people are self-medicating for what they think is difficulty sleeping, the concern is that even if a diagnosis of insomnia has been established, there could be another, ongoing sleep disorder that may be undiagnosed, which might be causing the problem with insomnia,” he said in an interview.

“For example, obstructive sleep apnea might be causing people to wake up in the night or even contribute to difficulty falling asleep in the first place. So medicating for something without a known diagnosis may leave an underlying sleep disorder untreated, which won’t help the patient in either the short or the long term,” Dr. Ramar said.
 

Causes for concern

“For those people who have COVID, we have seen quite a few sleep issues develop. Those were not reported in the actual study, but in the clinic and subsequent studies published from other places,” Dr. Gozal said.

“People who suffered from COVID, and even people who supposedly did very well and were virtually asymptomatic or maybe had only a headache or fever but did not need to go to the hospital, many of those people reported either excessive sleepiness for a long period of time, and would sleep 2 or 3 hours more per night. Or the opposite was reported: There were those that after recovering reported that they couldn’t sleep – they were sleeping 4 or 5 hours when they normally sleep 7 or 8,” he said.

It’s also unclear from current evidence whether the reported uptick in sleep problems is related to stress or, in patients who have had COVID-19 infections, to physiologic causes.

Dr. Gozal said that insomnia in the time of COVID-19 could be attributed to a number of factors such as less daily exposure to natural light from people sheltering indoors, stress related to financial or health worries, depression, or other psychological factors.

It’s also, possible, however, that COVID-19-related physiological changes could contribute to sleep disorders, he said, pointing to a recent study in the Journal of Experimental Medicine showing that SARS-CoV-2, the virus that causes COVID-19, can bind to neurons and cause metabolic changes in both infected and neighboring cells.

“My guess is that some of it is related more to behavioral impacts – people develop depression, changes in mood, anxiety, and so on, and all of these can translate into difficulties with sleep,” he said.

“It could be that in some instances – not very commonly – the virus will affect areas that control sleep in our brain, and that therefore we may see too much or too little sleep, and how to differentiate between all of these is the area that clearly needs to be explored, particularly in light of the finding that the virus can bind to brain cells and can induce substantial issues in the brain cells.”
 

Compromised immunity

It has been well documented that in addition to being, as Shakespeare called it, “the balm of hurt minds,” sleep has an important role in supporting the immune system.

“Sleep and immunity go together,” Dr. Ramar said. “When people have adequate sleep, their immune system is boosted. We know that there are good data from hepatitis A and hepatitis B vaccinations, and recently on flu vaccination, that if people get sufficient duration of sleep before and after they receive the shot, their likelihood of building an immune response to that particular vaccination tends to go up.”

It’s reasonable to assume that the same would hold true for COVID-19 vaccinations, but this has yet to be shown, he added.

“We do know from the previous studies that persistent sleep problems can make people more susceptible to infection or impair recovery; not yet, I believe, from the COVID-19 infection perspective,” Dr. Kendzerska said. “In our study, we did find that, among other factors, having a chronic illness was associated with new sleep difficulties during the pandemic. We did not look separately if sleep difficulties were associated with the COVID-19 infection or symptoms, but this is a great question to address with longitudinal data we have.”
 

What to do?

All three sleep experts contacted for this article agreed that for patients with insomnia, mitigating stress through relaxation techniques or cognitive behavioral therapy is more beneficial than medication.

“Medications, even over-the-counter medications, all have side effects, and if one is taking a medication that has stimulants in place, such as pseudoephedrine in antihistamine combinations, that can potentially contribute to or exacerbate any underlying sleep disorders,” Dr. Ramar said.

Dr. Kendzerska recommended reserving medications such as melatonin, a chronobiotic therapy, for patients with sleep disorders related to circadian rhythm problems, including a sleep phase delay. Supplemental, short-term treatment with hypnotic agents such as zolpidem (Ambien), eszopiclone (Lunesta), or zaleplon (Sonata) should be used only as a last resort, she said.

Sleep medicine specialists recommend good sleep hygiene as the best means of obtaining restful sleep, including regular bed and wake times, limited exposure to stressful news (including COVID-19 stories), reduced consumption of alcohol and stimulants such as coffee or caffeine drinks, avoiding use of electronic devices in bed or near bedtime, and healthy lifestyle, including diet and exercise.

They also frown on self-medication with over-the-counter aids, because these products may not be addressing the underlying issue, as noted before.

“It is also foreseeable that there may be an increase in individuals who may require professional guidance to taper off from sleeping medications started or increased during the pandemic. While some of these sleep problems may be transient, it should be a high priority to ensure they do not evolve into chronic sleep disorders,” Dr. Kendzerska and colleagues wrote.
 

Research avenues

If there’s anything that causes specialists to lose sleep, it’s the lack of data or evidence to guide clinical care and research. Dr. Gozal emphasized that little is still known about the potential central nervous system effects of COVID-19, and said that should be an important focus for research into the still novel coronavirus.

“What happens post COVID and how might that affect subsequent recovery is a great question, and I don’t think we have good data there,” Dr. Ramar said. “What we do know is that patients develop the symptoms of fatigue, disrupted sleep, even ongoing fever, and unfortunately, this may persist for a long period of time even among patients who have otherwise recovered from COVID-19. We know that leaving that untreated from a sleep disorder perspective can exacerbate their daytime symptoms, and that’s where I would strongly recommend that they seek help with a sleep provider or if there are symptoms other than insomnia at least with a primary care provider.”

Among the many losses suffered by millions worldwide during the COVID-19 pandemic, the loss of sleep may be the most widespread, with potentially long-lasting, negative consequences on physical, mental, and emotional health, sleep researchers have found.

Results from multiple studies and surveys conducted during the pandemic show that a majority of subjects report clinically meaningful changes in sleep quality, sleep patterns, and sleep disturbances.

klebercordeiro/Getty Images

Sleeping, more or less

A coauthor of that study, David Gozal, MD, FCCP, a pediatric pulmonologist and sleep medicine specialist at the University of Missouri in Columbia, said that the pandemic has had paradoxical effects on sleeps patterns for many.

“At the beginning, with the initial phases of lockdown for COVID, for most of the people whose jobs were not affected and who did not lose their jobs, [for whom] there was not the anxiety of being jobless and financially strapped, but who now were staying at home, there was actually a benefit. People started reporting getting more sleep and, more importantly, more vivid dreams and things of that nature,” he said in an interview.

“But as the lockdown progressed, we saw progressively and increasingly more people having difficulty falling asleep and staying asleep, using more medicines such as hypnotics to induce sleep, and we saw a 20% increase in the overall consumption of sleeping pills,” he said.

Similar results were seen in a cross-sectional survey of 843 adults in the United Kingdom, which showed that nearly 70% of participants reported a change in sleep patterns, only 45% reported having refreshing sleep, and 46% reported being sleepier during lockdown than before. Two-thirds of the respondents reported that the pandemic affected their mental health, and one-fourth reported increased alcohol consumption during lockdown. Those with suspected COVID-19 infections reported having more nightmares and abnormal sleep rhythms.

It is possible that the effects of COVID-19 infection on sleep may linger long after the infection itself has resolved, results of a cohort study from China suggest. As reported in The Lancet, among 1,655 patients discharged from the Jin Yin-tan hospital in Wuhan, 26% reported sleep disturbances 6 months after acute COVID-19 infection.
 

Self-medicating

Among 5,525 Canadians surveyed from April 3 through June 24, 2020, a large proportion reported the use of pharmacologic sleeps aids, said Tetyana Kendzerska, MD, PhD, assistant professor of medicine in the division of respirology at the University of Ottawa.

“At the time of the survey completion, 27% of participants reported taking sleeping aids (prescribed or [over] the counter); across the entire sample, 8% of respondents reported an increase in the frequency of sleeping medication use during the outbreak compared to before the outbreak,” she said in an interview.

Many people resort to self-medicating with over-the-counter preparations such as melatonin and pain-relief nighttime formulations containing diphenhydramine (Benadryl), a first-generation antihistamine with sedative properties, noted Kannan Ramar, MBBS, MD, a critical care, pulmonary, and sleep medicine specialist at the Mayo Clinic in Rochester, Minn., and current president of the American Academy of Sleep Medicine.

“When people are self-medicating for what they think is difficulty sleeping, the concern is that even if a diagnosis of insomnia has been established, there could be another, ongoing sleep disorder that may be undiagnosed, which might be causing the problem with insomnia,” he said in an interview.

“For example, obstructive sleep apnea might be causing people to wake up in the night or even contribute to difficulty falling asleep in the first place. So medicating for something without a known diagnosis may leave an underlying sleep disorder untreated, which won’t help the patient in either the short or the long term,” Dr. Ramar said.
 

Causes for concern

“For those people who have COVID, we have seen quite a few sleep issues develop. Those were not reported in the actual study, but in the clinic and subsequent studies published from other places,” Dr. Gozal said.

“People who suffered from COVID, and even people who supposedly did very well and were virtually asymptomatic or maybe had only a headache or fever but did not need to go to the hospital, many of those people reported either excessive sleepiness for a long period of time, and would sleep 2 or 3 hours more per night. Or the opposite was reported: There were those that after recovering reported that they couldn’t sleep – they were sleeping 4 or 5 hours when they normally sleep 7 or 8,” he said.

It’s also unclear from current evidence whether the reported uptick in sleep problems is related to stress or, in patients who have had COVID-19 infections, to physiologic causes.

Dr. Gozal said that insomnia in the time of COVID-19 could be attributed to a number of factors such as less daily exposure to natural light from people sheltering indoors, stress related to financial or health worries, depression, or other psychological factors.

It’s also, possible, however, that COVID-19-related physiological changes could contribute to sleep disorders, he said, pointing to a recent study in the Journal of Experimental Medicine showing that SARS-CoV-2, the virus that causes COVID-19, can bind to neurons and cause metabolic changes in both infected and neighboring cells.

“My guess is that some of it is related more to behavioral impacts – people develop depression, changes in mood, anxiety, and so on, and all of these can translate into difficulties with sleep,” he said.

“It could be that in some instances – not very commonly – the virus will affect areas that control sleep in our brain, and that therefore we may see too much or too little sleep, and how to differentiate between all of these is the area that clearly needs to be explored, particularly in light of the finding that the virus can bind to brain cells and can induce substantial issues in the brain cells.”
 

Compromised immunity

It has been well documented that in addition to being, as Shakespeare called it, “the balm of hurt minds,” sleep has an important role in supporting the immune system.

“Sleep and immunity go together,” Dr. Ramar said. “When people have adequate sleep, their immune system is boosted. We know that there are good data from hepatitis A and hepatitis B vaccinations, and recently on flu vaccination, that if people get sufficient duration of sleep before and after they receive the shot, their likelihood of building an immune response to that particular vaccination tends to go up.”

It’s reasonable to assume that the same would hold true for COVID-19 vaccinations, but this has yet to be shown, he added.

“We do know from the previous studies that persistent sleep problems can make people more susceptible to infection or impair recovery; not yet, I believe, from the COVID-19 infection perspective,” Dr. Kendzerska said. “In our study, we did find that, among other factors, having a chronic illness was associated with new sleep difficulties during the pandemic. We did not look separately if sleep difficulties were associated with the COVID-19 infection or symptoms, but this is a great question to address with longitudinal data we have.”
 

What to do?

All three sleep experts contacted for this article agreed that for patients with insomnia, mitigating stress through relaxation techniques or cognitive behavioral therapy is more beneficial than medication.

“Medications, even over-the-counter medications, all have side effects, and if one is taking a medication that has stimulants in place, such as pseudoephedrine in antihistamine combinations, that can potentially contribute to or exacerbate any underlying sleep disorders,” Dr. Ramar said.

Dr. Kendzerska recommended reserving medications such as melatonin, a chronobiotic therapy, for patients with sleep disorders related to circadian rhythm problems, including a sleep phase delay. Supplemental, short-term treatment with hypnotic agents such as zolpidem (Ambien), eszopiclone (Lunesta), or zaleplon (Sonata) should be used only as a last resort, she said.

Sleep medicine specialists recommend good sleep hygiene as the best means of obtaining restful sleep, including regular bed and wake times, limited exposure to stressful news (including COVID-19 stories), reduced consumption of alcohol and stimulants such as coffee or caffeine drinks, avoiding use of electronic devices in bed or near bedtime, and healthy lifestyle, including diet and exercise.

They also frown on self-medication with over-the-counter aids, because these products may not be addressing the underlying issue, as noted before.

“It is also foreseeable that there may be an increase in individuals who may require professional guidance to taper off from sleeping medications started or increased during the pandemic. While some of these sleep problems may be transient, it should be a high priority to ensure they do not evolve into chronic sleep disorders,” Dr. Kendzerska and colleagues wrote.
 

Research avenues

If there’s anything that causes specialists to lose sleep, it’s the lack of data or evidence to guide clinical care and research. Dr. Gozal emphasized that little is still known about the potential central nervous system effects of COVID-19, and said that should be an important focus for research into the still novel coronavirus.

“What happens post COVID and how might that affect subsequent recovery is a great question, and I don’t think we have good data there,” Dr. Ramar said. “What we do know is that patients develop the symptoms of fatigue, disrupted sleep, even ongoing fever, and unfortunately, this may persist for a long period of time even among patients who have otherwise recovered from COVID-19. We know that leaving that untreated from a sleep disorder perspective can exacerbate their daytime symptoms, and that’s where I would strongly recommend that they seek help with a sleep provider or if there are symptoms other than insomnia at least with a primary care provider.”

Among the many losses suffered by millions worldwide during the COVID-19 pandemic, the loss of sleep may be the most widespread, with potentially long-lasting, negative consequences on physical, mental, and emotional health, sleep researchers have found.

Results from multiple studies and surveys conducted during the pandemic show that a majority of subjects report clinically meaningful changes in sleep quality, sleep patterns, and sleep disturbances.

klebercordeiro/Getty Images

Sleeping, more or less

A coauthor of that study, David Gozal, MD, FCCP, a pediatric pulmonologist and sleep medicine specialist at the University of Missouri in Columbia, said that the pandemic has had paradoxical effects on sleeps patterns for many.

“At the beginning, with the initial phases of lockdown for COVID, for most of the people whose jobs were not affected and who did not lose their jobs, [for whom] there was not the anxiety of being jobless and financially strapped, but who now were staying at home, there was actually a benefit. People started reporting getting more sleep and, more importantly, more vivid dreams and things of that nature,” he said in an interview.

“But as the lockdown progressed, we saw progressively and increasingly more people having difficulty falling asleep and staying asleep, using more medicines such as hypnotics to induce sleep, and we saw a 20% increase in the overall consumption of sleeping pills,” he said.

Similar results were seen in a cross-sectional survey of 843 adults in the United Kingdom, which showed that nearly 70% of participants reported a change in sleep patterns, only 45% reported having refreshing sleep, and 46% reported being sleepier during lockdown than before. Two-thirds of the respondents reported that the pandemic affected their mental health, and one-fourth reported increased alcohol consumption during lockdown. Those with suspected COVID-19 infections reported having more nightmares and abnormal sleep rhythms.

It is possible that the effects of COVID-19 infection on sleep may linger long after the infection itself has resolved, results of a cohort study from China suggest. As reported in The Lancet, among 1,655 patients discharged from the Jin Yin-tan hospital in Wuhan, 26% reported sleep disturbances 6 months after acute COVID-19 infection.
 

Self-medicating

Among 5,525 Canadians surveyed from April 3 through June 24, 2020, a large proportion reported the use of pharmacologic sleeps aids, said Tetyana Kendzerska, MD, PhD, assistant professor of medicine in the division of respirology at the University of Ottawa.

“At the time of the survey completion, 27% of participants reported taking sleeping aids (prescribed or [over] the counter); across the entire sample, 8% of respondents reported an increase in the frequency of sleeping medication use during the outbreak compared to before the outbreak,” she said in an interview.

Many people resort to self-medicating with over-the-counter preparations such as melatonin and pain-relief nighttime formulations containing diphenhydramine (Benadryl), a first-generation antihistamine with sedative properties, noted Kannan Ramar, MBBS, MD, a critical care, pulmonary, and sleep medicine specialist at the Mayo Clinic in Rochester, Minn., and current president of the American Academy of Sleep Medicine.

“When people are self-medicating for what they think is difficulty sleeping, the concern is that even if a diagnosis of insomnia has been established, there could be another, ongoing sleep disorder that may be undiagnosed, which might be causing the problem with insomnia,” he said in an interview.

“For example, obstructive sleep apnea might be causing people to wake up in the night or even contribute to difficulty falling asleep in the first place. So medicating for something without a known diagnosis may leave an underlying sleep disorder untreated, which won’t help the patient in either the short or the long term,” Dr. Ramar said.
 

Causes for concern

“For those people who have COVID, we have seen quite a few sleep issues develop. Those were not reported in the actual study, but in the clinic and subsequent studies published from other places,” Dr. Gozal said.

“People who suffered from COVID, and even people who supposedly did very well and were virtually asymptomatic or maybe had only a headache or fever but did not need to go to the hospital, many of those people reported either excessive sleepiness for a long period of time, and would sleep 2 or 3 hours more per night. Or the opposite was reported: There were those that after recovering reported that they couldn’t sleep – they were sleeping 4 or 5 hours when they normally sleep 7 or 8,” he said.

It’s also unclear from current evidence whether the reported uptick in sleep problems is related to stress or, in patients who have had COVID-19 infections, to physiologic causes.

Dr. Gozal said that insomnia in the time of COVID-19 could be attributed to a number of factors such as less daily exposure to natural light from people sheltering indoors, stress related to financial or health worries, depression, or other psychological factors.

It’s also, possible, however, that COVID-19-related physiological changes could contribute to sleep disorders, he said, pointing to a recent study in the Journal of Experimental Medicine showing that SARS-CoV-2, the virus that causes COVID-19, can bind to neurons and cause metabolic changes in both infected and neighboring cells.

“My guess is that some of it is related more to behavioral impacts – people develop depression, changes in mood, anxiety, and so on, and all of these can translate into difficulties with sleep,” he said.

“It could be that in some instances – not very commonly – the virus will affect areas that control sleep in our brain, and that therefore we may see too much or too little sleep, and how to differentiate between all of these is the area that clearly needs to be explored, particularly in light of the finding that the virus can bind to brain cells and can induce substantial issues in the brain cells.”
 

Compromised immunity

It has been well documented that in addition to being, as Shakespeare called it, “the balm of hurt minds,” sleep has an important role in supporting the immune system.

“Sleep and immunity go together,” Dr. Ramar said. “When people have adequate sleep, their immune system is boosted. We know that there are good data from hepatitis A and hepatitis B vaccinations, and recently on flu vaccination, that if people get sufficient duration of sleep before and after they receive the shot, their likelihood of building an immune response to that particular vaccination tends to go up.”

It’s reasonable to assume that the same would hold true for COVID-19 vaccinations, but this has yet to be shown, he added.

“We do know from the previous studies that persistent sleep problems can make people more susceptible to infection or impair recovery; not yet, I believe, from the COVID-19 infection perspective,” Dr. Kendzerska said. “In our study, we did find that, among other factors, having a chronic illness was associated with new sleep difficulties during the pandemic. We did not look separately if sleep difficulties were associated with the COVID-19 infection or symptoms, but this is a great question to address with longitudinal data we have.”
 

What to do?

All three sleep experts contacted for this article agreed that for patients with insomnia, mitigating stress through relaxation techniques or cognitive behavioral therapy is more beneficial than medication.

“Medications, even over-the-counter medications, all have side effects, and if one is taking a medication that has stimulants in place, such as pseudoephedrine in antihistamine combinations, that can potentially contribute to or exacerbate any underlying sleep disorders,” Dr. Ramar said.

Dr. Kendzerska recommended reserving medications such as melatonin, a chronobiotic therapy, for patients with sleep disorders related to circadian rhythm problems, including a sleep phase delay. Supplemental, short-term treatment with hypnotic agents such as zolpidem (Ambien), eszopiclone (Lunesta), or zaleplon (Sonata) should be used only as a last resort, she said.

Sleep medicine specialists recommend good sleep hygiene as the best means of obtaining restful sleep, including regular bed and wake times, limited exposure to stressful news (including COVID-19 stories), reduced consumption of alcohol and stimulants such as coffee or caffeine drinks, avoiding use of electronic devices in bed or near bedtime, and healthy lifestyle, including diet and exercise.

They also frown on self-medication with over-the-counter aids, because these products may not be addressing the underlying issue, as noted before.

“It is also foreseeable that there may be an increase in individuals who may require professional guidance to taper off from sleeping medications started or increased during the pandemic. While some of these sleep problems may be transient, it should be a high priority to ensure they do not evolve into chronic sleep disorders,” Dr. Kendzerska and colleagues wrote.
 

Research avenues

If there’s anything that causes specialists to lose sleep, it’s the lack of data or evidence to guide clinical care and research. Dr. Gozal emphasized that little is still known about the potential central nervous system effects of COVID-19, and said that should be an important focus for research into the still novel coronavirus.

“What happens post COVID and how might that affect subsequent recovery is a great question, and I don’t think we have good data there,” Dr. Ramar said. “What we do know is that patients develop the symptoms of fatigue, disrupted sleep, even ongoing fever, and unfortunately, this may persist for a long period of time even among patients who have otherwise recovered from COVID-19. We know that leaving that untreated from a sleep disorder perspective can exacerbate their daytime symptoms, and that’s where I would strongly recommend that they seek help with a sleep provider or if there are symptoms other than insomnia at least with a primary care provider.”

The National Institutes of Health has dropped its recommendation against the inexpensive antiparasitic drug ivermectin for treatment of COVID-19, and the agency now advises it can’t recommend for or against its use, leaving the decision to physicians and their patients.

“Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19,” according to new NIH guidance released last week.

Passionate arguments have been waged for and against the drug’s use.

The NIH update disappointed members of the Front Line COVID-19 Critical Care Alliance (FLCCC), which outlined its case for endorsing ivermectin in a public statement Jan. 18. Point by point, the group of 10 physicians argued against each limitation that drove the NIH’s ruling.

The group’s members said that, although grateful the recommendation against the drug was dropped, a neutral approach is not acceptable as total U.S. deaths surpassed 400,000 since last spring – and currently approach 4,000 a day. Results from research are enough to support its use, and the drug will immediately save lives, they say.

“Patients do not have time to wait,” they write, “and we as health care providers in society do not have that time either.”

NIH, which in August had recommended against ivermectin’s use, invited the group to present evidence to its treatment guidance panel on Jan. 6 to detail the emerging science surrounding ivermectin. The group cited rapidly growing evidence of the drug’s effectiveness.

Pierre Kory, MD, president/cofounder of FLCCC and a pulmonary and critical care specialist at Aurora St. Luke’s Medical Center in Milwaukee, also spoke before a Senate panel on Dec. 8 in a widely shared impassioned video, touting ivermectin as a COVID-19 “miracle” drug, a term he said he doesn’t use lightly.

Dr. Kory pleaded with the NIH to consider the emerging data. “Please, I’m just asking that they review our manuscript,” he told the senators.

“We have immense amounts of data to show that ivermectin must be implemented and implemented now,” he said.
 

Some draw parallels to hydroxychloroquine

Critics have said there’s not enough data to institute a protocol, and some draw parallels to another repurposed drug – hydroxychloroquine (HCQ) – which was once considered a promising treatment for COVID-19, based on flawed and incomplete evidence, and now is not recommended.

Paul Sax, MD, a professor of medicine at Harvard and clinical director of the HIV program and division of infectious diseases at Brigham and Women’s Hospital in Boston, wrote in a blog post earlier this month in the New England Journal of Medicine Journal Watch that ivermectin has more robust evidence for it than HCQ ever did.

“But we’re not quite yet at the ‘practice changing’ level,” he writes. “Results from at least five randomized clinical trials are expected soon that might further inform the decision.”

He said the best argument for the drug is seen in this explanation of a meta-analysis of studies of between 100 and 500 patients by Andrew Hill, MD, with the department of pharmacology, University of Liverpool (England).

Dr. Sax advises against two biases in considering ivermectin. One is assuming that because HCQ failed, other antiparasitic drugs will too.

The second bias to avoid, he says, is discounting studies done in low- and middle-income countries because “they weren’t done in the right places.”

“That’s not just bias,” he says. “It’s also snobbery.”

Ivermectin has been approved by the U.S. Food and Drug Administration for treatment of onchocerciasis (river blindness) and strongyloidiasis, but is not FDA-approved for the treatment of any viral infection. It also is sometimes used to treat animals.

In dropping the recommendation against ivermectin, the NIH gave it the same neutral declaration as monoclonal antibodies and convalescent plasma.
 

Some physicians say they won’t prescribe it

Some physicians say they won’t be recommending it to their COVID-19 patients.

Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins University Center for Health Security in Baltimore,said in an interview that the NIH update hasn’t changed his mind and he isn’t prescribing it for his patients.

He said although “there’s enough of a signal” that he would like to see more data, “we haven’t seen anything in terms of a really robust study.”

He noted that the Infectious Diseases Society of America has 15 recommendations for COVID-19 treatment “and not one of them has to do with ivermectin.”

He added, “It’s not enough to see if it works, but we need to see who it works in and when it works in them.”

He also acknowledged that “some prominent physicians” are recommending it.

Among them is Paul Marik, MD, endowed professor of medicine and chief of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk. A cofounder of FLCCC, Dr. Marik has championed ivermectin and developed a protocol for its use to prevent and treat COVID-19.

The data surrounding ivermectin have met with hope, criticism, and warnings.

Australian researchers published a study ahead of print in Antiviral Research that found ivermectin inhibited the replication of SARS-CoV-2 in a laboratory setting.

The study concluded that the drug resulted post infection in a 5,000-fold reduction in viral RNA at 48 hours. After that study, however, the FDA in April warned consumers not to self-medicate with ivermectin products intended for animals.

The NIH acknowledged that several randomized trials and retrospective studies of ivermectin use in patients with COVID-19 have now been published in peer-reviewed journals or on preprint servers.

“Some clinical studies showed no benefits or worsening of disease after ivermectin use, whereas others reported shorter time to resolution of disease manifestations attributed to COVID-19, greater reduction in inflammatory markers, shorter time to viral clearance, or lower mortality rates in patients who received ivermectin than in patients who received comparator drugs or placebo,” the NIH guidance reads.

The NIH acknowledges limitations: the studies have been small; doses of ivermectin have varied; some patients were taking other medications at the same time (including doxycycline, hydroxychloroquine, azithromycin, zinc, and corticosteroids, which may be potential confounders); and patients’ severity of COVID was not always clearly described in the studies.

Nasia Safdar, MD, medical director of infection prevention at the University of Wisconsin Hospital in Madison, told this news organization she agrees more research is needed before ivermectin is recommended by regulatory bodies for COVID-19.

That said, Dr. Safdar added, “in individual circumstances if a physician is confronted with a patient in dire straits and you’re not sure what to do, might you consider it? I think after a discussion with the patient, perhaps, but the level of evidence certainly doesn’t rise to the level of a policy.”

A downside of recommending a treatment without conclusive data, even if harm isn’t the primary concern, she said, is that supplies could dwindle for its intended use in other diseases. Also, premature approval can limit the robust research needed to see not only whether it works better for prevention or treatment, but also if it’s effective depending on patient populations and the severity of COVID-19.

Dr. Adalja and Dr. Safdar have disclosed no relevant financial relationships.

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

The National Institutes of Health has dropped its recommendation against the inexpensive antiparasitic drug ivermectin for treatment of COVID-19, and the agency now advises it can’t recommend for or against its use, leaving the decision to physicians and their patients.

“Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19,” according to new NIH guidance released last week.

Passionate arguments have been waged for and against the drug’s use.

The NIH update disappointed members of the Front Line COVID-19 Critical Care Alliance (FLCCC), which outlined its case for endorsing ivermectin in a public statement Jan. 18. Point by point, the group of 10 physicians argued against each limitation that drove the NIH’s ruling.

The group’s members said that, although grateful the recommendation against the drug was dropped, a neutral approach is not acceptable as total U.S. deaths surpassed 400,000 since last spring – and currently approach 4,000 a day. Results from research are enough to support its use, and the drug will immediately save lives, they say.

“Patients do not have time to wait,” they write, “and we as health care providers in society do not have that time either.”

NIH, which in August had recommended against ivermectin’s use, invited the group to present evidence to its treatment guidance panel on Jan. 6 to detail the emerging science surrounding ivermectin. The group cited rapidly growing evidence of the drug’s effectiveness.

Pierre Kory, MD, president/cofounder of FLCCC and a pulmonary and critical care specialist at Aurora St. Luke’s Medical Center in Milwaukee, also spoke before a Senate panel on Dec. 8 in a widely shared impassioned video, touting ivermectin as a COVID-19 “miracle” drug, a term he said he doesn’t use lightly.

Dr. Kory pleaded with the NIH to consider the emerging data. “Please, I’m just asking that they review our manuscript,” he told the senators.

“We have immense amounts of data to show that ivermectin must be implemented and implemented now,” he said.
 

Some draw parallels to hydroxychloroquine

Critics have said there’s not enough data to institute a protocol, and some draw parallels to another repurposed drug – hydroxychloroquine (HCQ) – which was once considered a promising treatment for COVID-19, based on flawed and incomplete evidence, and now is not recommended.

Paul Sax, MD, a professor of medicine at Harvard and clinical director of the HIV program and division of infectious diseases at Brigham and Women’s Hospital in Boston, wrote in a blog post earlier this month in the New England Journal of Medicine Journal Watch that ivermectin has more robust evidence for it than HCQ ever did.

“But we’re not quite yet at the ‘practice changing’ level,” he writes. “Results from at least five randomized clinical trials are expected soon that might further inform the decision.”

He said the best argument for the drug is seen in this explanation of a meta-analysis of studies of between 100 and 500 patients by Andrew Hill, MD, with the department of pharmacology, University of Liverpool (England).

Dr. Sax advises against two biases in considering ivermectin. One is assuming that because HCQ failed, other antiparasitic drugs will too.

The second bias to avoid, he says, is discounting studies done in low- and middle-income countries because “they weren’t done in the right places.”

“That’s not just bias,” he says. “It’s also snobbery.”

Ivermectin has been approved by the U.S. Food and Drug Administration for treatment of onchocerciasis (river blindness) and strongyloidiasis, but is not FDA-approved for the treatment of any viral infection. It also is sometimes used to treat animals.

In dropping the recommendation against ivermectin, the NIH gave it the same neutral declaration as monoclonal antibodies and convalescent plasma.
 

Some physicians say they won’t prescribe it

Some physicians say they won’t be recommending it to their COVID-19 patients.

Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins University Center for Health Security in Baltimore,said in an interview that the NIH update hasn’t changed his mind and he isn’t prescribing it for his patients.

He said although “there’s enough of a signal” that he would like to see more data, “we haven’t seen anything in terms of a really robust study.”

He noted that the Infectious Diseases Society of America has 15 recommendations for COVID-19 treatment “and not one of them has to do with ivermectin.”

He added, “It’s not enough to see if it works, but we need to see who it works in and when it works in them.”

He also acknowledged that “some prominent physicians” are recommending it.

Among them is Paul Marik, MD, endowed professor of medicine and chief of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk. A cofounder of FLCCC, Dr. Marik has championed ivermectin and developed a protocol for its use to prevent and treat COVID-19.

The data surrounding ivermectin have met with hope, criticism, and warnings.

Australian researchers published a study ahead of print in Antiviral Research that found ivermectin inhibited the replication of SARS-CoV-2 in a laboratory setting.

The study concluded that the drug resulted post infection in a 5,000-fold reduction in viral RNA at 48 hours. After that study, however, the FDA in April warned consumers not to self-medicate with ivermectin products intended for animals.

The NIH acknowledged that several randomized trials and retrospective studies of ivermectin use in patients with COVID-19 have now been published in peer-reviewed journals or on preprint servers.

“Some clinical studies showed no benefits or worsening of disease after ivermectin use, whereas others reported shorter time to resolution of disease manifestations attributed to COVID-19, greater reduction in inflammatory markers, shorter time to viral clearance, or lower mortality rates in patients who received ivermectin than in patients who received comparator drugs or placebo,” the NIH guidance reads.

The NIH acknowledges limitations: the studies have been small; doses of ivermectin have varied; some patients were taking other medications at the same time (including doxycycline, hydroxychloroquine, azithromycin, zinc, and corticosteroids, which may be potential confounders); and patients’ severity of COVID was not always clearly described in the studies.

Nasia Safdar, MD, medical director of infection prevention at the University of Wisconsin Hospital in Madison, told this news organization she agrees more research is needed before ivermectin is recommended by regulatory bodies for COVID-19.

That said, Dr. Safdar added, “in individual circumstances if a physician is confronted with a patient in dire straits and you’re not sure what to do, might you consider it? I think after a discussion with the patient, perhaps, but the level of evidence certainly doesn’t rise to the level of a policy.”

A downside of recommending a treatment without conclusive data, even if harm isn’t the primary concern, she said, is that supplies could dwindle for its intended use in other diseases. Also, premature approval can limit the robust research needed to see not only whether it works better for prevention or treatment, but also if it’s effective depending on patient populations and the severity of COVID-19.

Dr. Adalja and Dr. Safdar have disclosed no relevant financial relationships.

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

The National Institutes of Health has dropped its recommendation against the inexpensive antiparasitic drug ivermectin for treatment of COVID-19, and the agency now advises it can’t recommend for or against its use, leaving the decision to physicians and their patients.

“Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19,” according to new NIH guidance released last week.

Passionate arguments have been waged for and against the drug’s use.

The NIH update disappointed members of the Front Line COVID-19 Critical Care Alliance (FLCCC), which outlined its case for endorsing ivermectin in a public statement Jan. 18. Point by point, the group of 10 physicians argued against each limitation that drove the NIH’s ruling.

The group’s members said that, although grateful the recommendation against the drug was dropped, a neutral approach is not acceptable as total U.S. deaths surpassed 400,000 since last spring – and currently approach 4,000 a day. Results from research are enough to support its use, and the drug will immediately save lives, they say.

“Patients do not have time to wait,” they write, “and we as health care providers in society do not have that time either.”

NIH, which in August had recommended against ivermectin’s use, invited the group to present evidence to its treatment guidance panel on Jan. 6 to detail the emerging science surrounding ivermectin. The group cited rapidly growing evidence of the drug’s effectiveness.

Pierre Kory, MD, president/cofounder of FLCCC and a pulmonary and critical care specialist at Aurora St. Luke’s Medical Center in Milwaukee, also spoke before a Senate panel on Dec. 8 in a widely shared impassioned video, touting ivermectin as a COVID-19 “miracle” drug, a term he said he doesn’t use lightly.

Dr. Kory pleaded with the NIH to consider the emerging data. “Please, I’m just asking that they review our manuscript,” he told the senators.

“We have immense amounts of data to show that ivermectin must be implemented and implemented now,” he said.
 

Some draw parallels to hydroxychloroquine

Critics have said there’s not enough data to institute a protocol, and some draw parallels to another repurposed drug – hydroxychloroquine (HCQ) – which was once considered a promising treatment for COVID-19, based on flawed and incomplete evidence, and now is not recommended.

Paul Sax, MD, a professor of medicine at Harvard and clinical director of the HIV program and division of infectious diseases at Brigham and Women’s Hospital in Boston, wrote in a blog post earlier this month in the New England Journal of Medicine Journal Watch that ivermectin has more robust evidence for it than HCQ ever did.

“But we’re not quite yet at the ‘practice changing’ level,” he writes. “Results from at least five randomized clinical trials are expected soon that might further inform the decision.”

He said the best argument for the drug is seen in this explanation of a meta-analysis of studies of between 100 and 500 patients by Andrew Hill, MD, with the department of pharmacology, University of Liverpool (England).

Dr. Sax advises against two biases in considering ivermectin. One is assuming that because HCQ failed, other antiparasitic drugs will too.

The second bias to avoid, he says, is discounting studies done in low- and middle-income countries because “they weren’t done in the right places.”

“That’s not just bias,” he says. “It’s also snobbery.”

Ivermectin has been approved by the U.S. Food and Drug Administration for treatment of onchocerciasis (river blindness) and strongyloidiasis, but is not FDA-approved for the treatment of any viral infection. It also is sometimes used to treat animals.

In dropping the recommendation against ivermectin, the NIH gave it the same neutral declaration as monoclonal antibodies and convalescent plasma.
 

Some physicians say they won’t prescribe it

Some physicians say they won’t be recommending it to their COVID-19 patients.

Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins University Center for Health Security in Baltimore,said in an interview that the NIH update hasn’t changed his mind and he isn’t prescribing it for his patients.

He said although “there’s enough of a signal” that he would like to see more data, “we haven’t seen anything in terms of a really robust study.”

He noted that the Infectious Diseases Society of America has 15 recommendations for COVID-19 treatment “and not one of them has to do with ivermectin.”

He added, “It’s not enough to see if it works, but we need to see who it works in and when it works in them.”

He also acknowledged that “some prominent physicians” are recommending it.

Among them is Paul Marik, MD, endowed professor of medicine and chief of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk. A cofounder of FLCCC, Dr. Marik has championed ivermectin and developed a protocol for its use to prevent and treat COVID-19.

The data surrounding ivermectin have met with hope, criticism, and warnings.

Australian researchers published a study ahead of print in Antiviral Research that found ivermectin inhibited the replication of SARS-CoV-2 in a laboratory setting.

The study concluded that the drug resulted post infection in a 5,000-fold reduction in viral RNA at 48 hours. After that study, however, the FDA in April warned consumers not to self-medicate with ivermectin products intended for animals.

The NIH acknowledged that several randomized trials and retrospective studies of ivermectin use in patients with COVID-19 have now been published in peer-reviewed journals or on preprint servers.

“Some clinical studies showed no benefits or worsening of disease after ivermectin use, whereas others reported shorter time to resolution of disease manifestations attributed to COVID-19, greater reduction in inflammatory markers, shorter time to viral clearance, or lower mortality rates in patients who received ivermectin than in patients who received comparator drugs or placebo,” the NIH guidance reads.

The NIH acknowledges limitations: the studies have been small; doses of ivermectin have varied; some patients were taking other medications at the same time (including doxycycline, hydroxychloroquine, azithromycin, zinc, and corticosteroids, which may be potential confounders); and patients’ severity of COVID was not always clearly described in the studies.

Nasia Safdar, MD, medical director of infection prevention at the University of Wisconsin Hospital in Madison, told this news organization she agrees more research is needed before ivermectin is recommended by regulatory bodies for COVID-19.

That said, Dr. Safdar added, “in individual circumstances if a physician is confronted with a patient in dire straits and you’re not sure what to do, might you consider it? I think after a discussion with the patient, perhaps, but the level of evidence certainly doesn’t rise to the level of a policy.”

A downside of recommending a treatment without conclusive data, even if harm isn’t the primary concern, she said, is that supplies could dwindle for its intended use in other diseases. Also, premature approval can limit the robust research needed to see not only whether it works better for prevention or treatment, but also if it’s effective depending on patient populations and the severity of COVID-19.

Dr. Adalja and Dr. Safdar have disclosed no relevant financial relationships.

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

Key clinical point: Interictal plasma amylin levels are higher in patients with chronic migraine and may serve as a better diagnostic marker than calcitonin gene-related peptide (CGRP).

Major finding: Plasma amylin levels were higher in chronic migraine patients than in episodic migraine patients and healthy controls (both P less than. 0001). Diagnostic performance was better with plasma amylin than CGRP in differentiating chronic migraine from healthy controls in adults.

Study details: The data come from a prospective case-controlled study involving 191 patients with chronic migraine, 58 patients with episodic migraine, and 68 healthy controls.

Disclosures: This study was funded by the Spanish Research Network on Cerebrovascular Diseases, Center for Applied Medical Research, University of Navarra, and Spanish Ministry of Economy and Competitiveness. The authors declared no conflicts of interest.

Source: Irimia P et al. Cephalalgia. 2020 Dec 3. doi: 10.1177/0333102420977106.

Key clinical point: Interictal plasma amylin levels are higher in patients with chronic migraine and may serve as a better diagnostic marker than calcitonin gene-related peptide (CGRP).

Major finding: Plasma amylin levels were higher in chronic migraine patients than in episodic migraine patients and healthy controls (both P less than. 0001). Diagnostic performance was better with plasma amylin than CGRP in differentiating chronic migraine from healthy controls in adults.

Study details: The data come from a prospective case-controlled study involving 191 patients with chronic migraine, 58 patients with episodic migraine, and 68 healthy controls.

Disclosures: This study was funded by the Spanish Research Network on Cerebrovascular Diseases, Center for Applied Medical Research, University of Navarra, and Spanish Ministry of Economy and Competitiveness. The authors declared no conflicts of interest.

Source: Irimia P et al. Cephalalgia. 2020 Dec 3. doi: 10.1177/0333102420977106.

Key clinical point: Interictal plasma amylin levels are higher in patients with chronic migraine and may serve as a better diagnostic marker than calcitonin gene-related peptide (CGRP).

Major finding: Plasma amylin levels were higher in chronic migraine patients than in episodic migraine patients and healthy controls (both P less than. 0001). Diagnostic performance was better with plasma amylin than CGRP in differentiating chronic migraine from healthy controls in adults.

Study details: The data come from a prospective case-controlled study involving 191 patients with chronic migraine, 58 patients with episodic migraine, and 68 healthy controls.

Disclosures: This study was funded by the Spanish Research Network on Cerebrovascular Diseases, Center for Applied Medical Research, University of Navarra, and Spanish Ministry of Economy and Competitiveness. The authors declared no conflicts of interest.

Source: Irimia P et al. Cephalalgia. 2020 Dec 3. doi: 10.1177/0333102420977106.

Key clinical point: Sex differences in recovery time were observed in pediatric patients with mild traumatic brain injury or concussion, with girls and women taking longer to recover than boys and men. Patients with comorbidities of emotional distress (i.e., anxiety or depression) and migraine recovered more slowly, independent of sex.

Major finding: Girls and women experienced slower recovery (persistent symptoms after injury: week 4, 81.6% vs. 71.2%; week 8, 58.9% vs. 44.3%; and week 12, 42.6% vs. 30.2%; P = .01) and were more likely to have preexisting anxiety (26.7% vs. 18.7%) vs. boys and men. Patients with a history of emotional distress (persistent symptoms after injury: week 4, 80.9% vs. 75.6%; week 8, 57.8% vs. 50.5%; and week 12, 48.0% vs. 33.3%; P = .009) and migraine (persistent symptoms after injury: week 4, 87.3% vs. 73.9%; week 8, 67.7% vs. 49.0%; and week 12, 55.7% vs. 33.2%; P = .001) recovered more slowly vs. those without.

Study details: A prospective cohort study of 600 pediatric patients (54% females, 72.5% adolescents) enrolled at multicenter concussion specialty clinics from the Four Corners Youth Consortium from December 2017 to July 2019.

Disclosures: The study was supported by funds from the UCLA Steve Tisch BrainSPORT Program, the Easton Clinic for Brain Health, the UCLA Brain Injury Research Center, Stan and Patti Silver, the Satterberg Foundation, and the Sports Institute at UW Medicine. The presenting author had no disclosures. Three coauthors reported various disclosures.

Source: Rosenbaum PE et al. JAMA Netw Open. 2020 Nov 2. doi: 10.1001/jamanetworkopen.2020.21463.

Key clinical point: Sex differences in recovery time were observed in pediatric patients with mild traumatic brain injury or concussion, with girls and women taking longer to recover than boys and men. Patients with comorbidities of emotional distress (i.e., anxiety or depression) and migraine recovered more slowly, independent of sex.

Major finding: Girls and women experienced slower recovery (persistent symptoms after injury: week 4, 81.6% vs. 71.2%; week 8, 58.9% vs. 44.3%; and week 12, 42.6% vs. 30.2%; P = .01) and were more likely to have preexisting anxiety (26.7% vs. 18.7%) vs. boys and men. Patients with a history of emotional distress (persistent symptoms after injury: week 4, 80.9% vs. 75.6%; week 8, 57.8% vs. 50.5%; and week 12, 48.0% vs. 33.3%; P = .009) and migraine (persistent symptoms after injury: week 4, 87.3% vs. 73.9%; week 8, 67.7% vs. 49.0%; and week 12, 55.7% vs. 33.2%; P = .001) recovered more slowly vs. those without.

Study details: A prospective cohort study of 600 pediatric patients (54% females, 72.5% adolescents) enrolled at multicenter concussion specialty clinics from the Four Corners Youth Consortium from December 2017 to July 2019.

Disclosures: The study was supported by funds from the UCLA Steve Tisch BrainSPORT Program, the Easton Clinic for Brain Health, the UCLA Brain Injury Research Center, Stan and Patti Silver, the Satterberg Foundation, and the Sports Institute at UW Medicine. The presenting author had no disclosures. Three coauthors reported various disclosures.

Source: Rosenbaum PE et al. JAMA Netw Open. 2020 Nov 2. doi: 10.1001/jamanetworkopen.2020.21463.

Key clinical point: Sex differences in recovery time were observed in pediatric patients with mild traumatic brain injury or concussion, with girls and women taking longer to recover than boys and men. Patients with comorbidities of emotional distress (i.e., anxiety or depression) and migraine recovered more slowly, independent of sex.

Major finding: Girls and women experienced slower recovery (persistent symptoms after injury: week 4, 81.6% vs. 71.2%; week 8, 58.9% vs. 44.3%; and week 12, 42.6% vs. 30.2%; P = .01) and were more likely to have preexisting anxiety (26.7% vs. 18.7%) vs. boys and men. Patients with a history of emotional distress (persistent symptoms after injury: week 4, 80.9% vs. 75.6%; week 8, 57.8% vs. 50.5%; and week 12, 48.0% vs. 33.3%; P = .009) and migraine (persistent symptoms after injury: week 4, 87.3% vs. 73.9%; week 8, 67.7% vs. 49.0%; and week 12, 55.7% vs. 33.2%; P = .001) recovered more slowly vs. those without.

Study details: A prospective cohort study of 600 pediatric patients (54% females, 72.5% adolescents) enrolled at multicenter concussion specialty clinics from the Four Corners Youth Consortium from December 2017 to July 2019.

Disclosures: The study was supported by funds from the UCLA Steve Tisch BrainSPORT Program, the Easton Clinic for Brain Health, the UCLA Brain Injury Research Center, Stan and Patti Silver, the Satterberg Foundation, and the Sports Institute at UW Medicine. The presenting author had no disclosures. Three coauthors reported various disclosures.

Source: Rosenbaum PE et al. JAMA Netw Open. 2020 Nov 2. doi: 10.1001/jamanetworkopen.2020.21463.

Key clinical point: This meta-analysis suggests that ginger is safe and effective in treating migraine patients with pain outcomes assessed at 2 hours.

Major finding: Ginger treatment was associated with substantially improved pain-free at 2 hours (risk ratio [RR], 1.79; P = .04) and decreased pain scores at 2 hours (mean difference, −1.27; P less than .00001), but showed no notable influence on treatment response (RR, 2.04; P = .43). The incidence of nausea and vomiting was lower in the ginger group vs. control group. The total adverse events were similar between groups (RR, 0.80; P = .44).

Study details: A meta-analysis of 3 randomized controlled trials including 227 participants.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Chen L et al. Am J Emerg Med. 2020 Nov 17. doi: 10.1016/j.ajem.2020.11.030.

Key clinical point: This meta-analysis suggests that ginger is safe and effective in treating migraine patients with pain outcomes assessed at 2 hours.

Major finding: Ginger treatment was associated with substantially improved pain-free at 2 hours (risk ratio [RR], 1.79; P = .04) and decreased pain scores at 2 hours (mean difference, −1.27; P less than .00001), but showed no notable influence on treatment response (RR, 2.04; P = .43). The incidence of nausea and vomiting was lower in the ginger group vs. control group. The total adverse events were similar between groups (RR, 0.80; P = .44).

Study details: A meta-analysis of 3 randomized controlled trials including 227 participants.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Chen L et al. Am J Emerg Med. 2020 Nov 17. doi: 10.1016/j.ajem.2020.11.030.

Key clinical point: This meta-analysis suggests that ginger is safe and effective in treating migraine patients with pain outcomes assessed at 2 hours.

Major finding: Ginger treatment was associated with substantially improved pain-free at 2 hours (risk ratio [RR], 1.79; P = .04) and decreased pain scores at 2 hours (mean difference, −1.27; P less than .00001), but showed no notable influence on treatment response (RR, 2.04; P = .43). The incidence of nausea and vomiting was lower in the ginger group vs. control group. The total adverse events were similar between groups (RR, 0.80; P = .44).

Study details: A meta-analysis of 3 randomized controlled trials including 227 participants.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Chen L et al. Am J Emerg Med. 2020 Nov 17. doi: 10.1016/j.ajem.2020.11.030.

Key clinical point: Along with its efficacy as a migraine preventive treatment, fremanezumab demonstrates the potential benefit for reversion from chronic migraine (CM) to episodic migraine (EM).

Major finding: The rates of reversion from CM to EM were higher in patients treated with fremanezumab vs. those treated with placebo, when reversion was defined either as an average of less than 15 headache days per month during the 3-month treatment period (quarterly: 50.5%; P = .108 and monthly: 53.7%; P = .012 vs. placebo: 44.5%) or, more stringently, as less than 15 headache days per month at months 1, 2, and 3 (quarterly: 31.2%; P = .008 and monthly: 33.7%; P = .001 vs. placebo: 22.4%).

Study details: The findings are based on a post hoc analysis of the HALO CM trial. Patients with CM (n=1,088) were randomly assigned to 1 of the 3 treatment groups (fremanezumab quarterly, n=376; fremanezumab monthly, n=379; or placebo, n=375).

Disclosures: The study was funded by Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel. Some study investigators reported being an employee of Teva Branded Pharmaceutical Products R&D, Inc., receiving honoraria from, and/or consulting for Teva Pharmaceuticals.

Source: Lipton RB et al. Headache. 2020 Nov 11. doi: 10.1111/head.13997.

Key clinical point: Along with its efficacy as a migraine preventive treatment, fremanezumab demonstrates the potential benefit for reversion from chronic migraine (CM) to episodic migraine (EM).

Major finding: The rates of reversion from CM to EM were higher in patients treated with fremanezumab vs. those treated with placebo, when reversion was defined either as an average of less than 15 headache days per month during the 3-month treatment period (quarterly: 50.5%; P = .108 and monthly: 53.7%; P = .012 vs. placebo: 44.5%) or, more stringently, as less than 15 headache days per month at months 1, 2, and 3 (quarterly: 31.2%; P = .008 and monthly: 33.7%; P = .001 vs. placebo: 22.4%).

Study details: The findings are based on a post hoc analysis of the HALO CM trial. Patients with CM (n=1,088) were randomly assigned to 1 of the 3 treatment groups (fremanezumab quarterly, n=376; fremanezumab monthly, n=379; or placebo, n=375).

Disclosures: The study was funded by Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel. Some study investigators reported being an employee of Teva Branded Pharmaceutical Products R&D, Inc., receiving honoraria from, and/or consulting for Teva Pharmaceuticals.

Source: Lipton RB et al. Headache. 2020 Nov 11. doi: 10.1111/head.13997.

Key clinical point: Along with its efficacy as a migraine preventive treatment, fremanezumab demonstrates the potential benefit for reversion from chronic migraine (CM) to episodic migraine (EM).

Major finding: The rates of reversion from CM to EM were higher in patients treated with fremanezumab vs. those treated with placebo, when reversion was defined either as an average of less than 15 headache days per month during the 3-month treatment period (quarterly: 50.5%; P = .108 and monthly: 53.7%; P = .012 vs. placebo: 44.5%) or, more stringently, as less than 15 headache days per month at months 1, 2, and 3 (quarterly: 31.2%; P = .008 and monthly: 33.7%; P = .001 vs. placebo: 22.4%).

Study details: The findings are based on a post hoc analysis of the HALO CM trial. Patients with CM (n=1,088) were randomly assigned to 1 of the 3 treatment groups (fremanezumab quarterly, n=376; fremanezumab monthly, n=379; or placebo, n=375).

Disclosures: The study was funded by Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel. Some study investigators reported being an employee of Teva Branded Pharmaceutical Products R&D, Inc., receiving honoraria from, and/or consulting for Teva Pharmaceuticals.

Source: Lipton RB et al. Headache. 2020 Nov 11. doi: 10.1111/head.13997.

A combination treatment of neutralizing monoclonal antibodies bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 at day 11 compared with placebo among nonhospitalized patients who had mild to moderate COVID-19, new data indicate.

However, bamlanivimab alone in three different single-infusion doses showed no significant reduction in viral load, compared with placebo, according to the phase 2/3 study by Robert L. Gottlieb, MD, PhD, of the Baylor University Medical Center and the Baylor Scott & White Research Institute, both in Dallas, and colleagues.

Findings from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) study were published online Jan. 21 in JAMA. The results represent findings through Oct. 6, 2020.

BLAZE-1 was funded by Eli Lilly, which makes both of the antispike neutralizing antibodies. The trial was conducted at 49 U.S. centers and included 613 outpatients who tested positive for SARS-CoV-2 and had one or more mild to moderate symptoms.

Patients were randomized to one of five groups (four treatment groups and a placebo control), and researchers analyzed between-group differences.

All four treatment arms suggest a trend toward reduction in viral load, which was the primary endpoint of the trial, but only the combination showed a statistically significant reduction.

The average age of patients was 44.7 years, 54.6% were female, 42.5% were Hispanic, and 67.1% had at least one risk factor for severe COVID-19 (aged ≥55 years, body mass index of at least 30, or relevant comorbidity such as hypertension).

Among secondary outcomes, there were no consistent differences between the monotherapy groups or the combination group versus placebo for the other measures of viral load or clinical symptom scores.

The proportion of patients who had COVID-19–related hospitalizations or ED visits was 5.8% (nine events) for placebo; 1.0% (one event) for the 700-mg group; 1.9% (two events) for 2,800 mg; 2.0% (two events) for 7,000 mg; and 0.9% (one event) for combination treatment.

“Combining these two neutralizing monoclonal antibodies in clinical use may enhance viral load reduction and decrease treatment-emergent resistant variants,” the authors concluded.
 

Safety profile comparison

As for adverse events, immediate hypersensitivity reactions were reported in nine patients (six bamlanivimab, two combination treatment, and one placebo). No deaths occurred during the study.

Serious adverse events unrelated to SARS-CoV-2 infection or considered related to the study drug occurred in 0% (0/309) of patients in the bamlanivimab monotherapy groups; in 0.9% (1/112) of patients in the combination group; and in 0.6% (1/156) of patients in the placebo group.

The serious adverse event in the combination group was a urinary tract infection deemed unrelated to the study drug, the authors wrote.

The two most frequently reported side effects were nausea (3.0% for the 700-mg group; 3.7% for the 2,800-mg group; 5.0% for the 7,000-mg group; 3.6% for the combination group; and 3.8% for the placebo group) and diarrhea (1.0%, 1.9%, 5.9%, 0.9%, and 4.5%, respectively).

The authors included in the study’s limitations that the primary endpoint at day 11 may have been too late to best detect treatment effects.

“All patients, including those who received placebo, demonstrated substantial viral reduction by day 11,” they noted. “An earlier time point like day 3 or day 7 could possibly have been more appropriate to measure viral load.”

Currently, only remdesivir has been approved by the Food and Drug Administration for treating COVID-19, but convalescent plasma and neutralizing monoclonal antibodies have been granted emergency-use authorization.

In an accompanying editor’s note, Preeti N. Malani, MD, with the division of infectious diseases at the University of Michigan, Ann Arbor, and associate editor of JAMA, and Robert M. Golub, MD, deputy editor of JAMA, pointed out that these results differ from an earlier interim analysis of BLAZE-1 data.

A previous publication by Peter Chen, MD, with the department of medicine at Cedars Sinai Medical Center, Los Angeles, compared the three monotherapy groups (no combination group) with placebo, and in that study the 2,800-mg dose of bamlanivimab versus placebo achieved statistical significance for reduction in viral load from baseline at day 11, whereas the other two doses did not.

The editors explain that, in the study by Dr. Chen, “Follow-up for the placebo group was incomplete at the time of the database lock on Sept. 5, 2020. In the final analysis reported in the current article, the database was locked on Oct. 6, 2020, and the longer follow-up for the placebo group, which is now complete, resulted in changes in the primary outcome among that group.”

They concluded: “The comparison of the monotherapy groups against the final results for the placebo group led to changes in the effect sizes,” and the statistical significance of the 2,800-mg group was erased.

The editors pointed out that monoclonal antibodies are likely to benefit certain patients but definitive answers regarding which patients will benefit and under what circumstances will likely take more time than clinicians have to make decisions on treatment.

Meanwhile, as this news organization reported, the United States has spent $375 million on bamlanivimab and $450 million on Regeneron’s monoclonal antibody cocktail of casirivimab plus imdevimab, with the promise to spend billions more.

However, 80% of the 660,000 doses delivered by the two companies are still sitting on shelves, federal officials said in a press briefing last week, because of doubts about efficacy, lack of resources for infusion centers, and questions on reimbursement.

“While the world waits for widespread administration of effective vaccines and additional data on treatments, local efforts should work to improve testing access and turnaround time and reduce logistical barriers to ensure that monoclonal therapies can be provided to patients who are most likely to benefit,” Dr. Malani and Dr. Golub wrote.

This trial was sponsored and funded by Eli Lilly. Dr. Gottlieb disclosed personal fees and nonfinancial support (medication for another trial) from Gilead Sciences and serving on an advisory board for Sentinel. Several coauthors have financial ties to Eli Lilly. Dr. Malani reported serving on the National Institute of Allergy and Infectious Diseases COVID-19 Preventive Monoclonal Antibody data and safety monitoring board but was not compensated. Dr. Golub disclosed no relevant financial relationships.

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

A combination treatment of neutralizing monoclonal antibodies bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 at day 11 compared with placebo among nonhospitalized patients who had mild to moderate COVID-19, new data indicate.

However, bamlanivimab alone in three different single-infusion doses showed no significant reduction in viral load, compared with placebo, according to the phase 2/3 study by Robert L. Gottlieb, MD, PhD, of the Baylor University Medical Center and the Baylor Scott & White Research Institute, both in Dallas, and colleagues.

Findings from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) study were published online Jan. 21 in JAMA. The results represent findings through Oct. 6, 2020.

BLAZE-1 was funded by Eli Lilly, which makes both of the antispike neutralizing antibodies. The trial was conducted at 49 U.S. centers and included 613 outpatients who tested positive for SARS-CoV-2 and had one or more mild to moderate symptoms.

Patients were randomized to one of five groups (four treatment groups and a placebo control), and researchers analyzed between-group differences.

All four treatment arms suggest a trend toward reduction in viral load, which was the primary endpoint of the trial, but only the combination showed a statistically significant reduction.

The average age of patients was 44.7 years, 54.6% were female, 42.5% were Hispanic, and 67.1% had at least one risk factor for severe COVID-19 (aged ≥55 years, body mass index of at least 30, or relevant comorbidity such as hypertension).

Among secondary outcomes, there were no consistent differences between the monotherapy groups or the combination group versus placebo for the other measures of viral load or clinical symptom scores.

The proportion of patients who had COVID-19–related hospitalizations or ED visits was 5.8% (nine events) for placebo; 1.0% (one event) for the 700-mg group; 1.9% (two events) for 2,800 mg; 2.0% (two events) for 7,000 mg; and 0.9% (one event) for combination treatment.

“Combining these two neutralizing monoclonal antibodies in clinical use may enhance viral load reduction and decrease treatment-emergent resistant variants,” the authors concluded.
 

Safety profile comparison

As for adverse events, immediate hypersensitivity reactions were reported in nine patients (six bamlanivimab, two combination treatment, and one placebo). No deaths occurred during the study.

Serious adverse events unrelated to SARS-CoV-2 infection or considered related to the study drug occurred in 0% (0/309) of patients in the bamlanivimab monotherapy groups; in 0.9% (1/112) of patients in the combination group; and in 0.6% (1/156) of patients in the placebo group.

The serious adverse event in the combination group was a urinary tract infection deemed unrelated to the study drug, the authors wrote.

The two most frequently reported side effects were nausea (3.0% for the 700-mg group; 3.7% for the 2,800-mg group; 5.0% for the 7,000-mg group; 3.6% for the combination group; and 3.8% for the placebo group) and diarrhea (1.0%, 1.9%, 5.9%, 0.9%, and 4.5%, respectively).

The authors included in the study’s limitations that the primary endpoint at day 11 may have been too late to best detect treatment effects.

“All patients, including those who received placebo, demonstrated substantial viral reduction by day 11,” they noted. “An earlier time point like day 3 or day 7 could possibly have been more appropriate to measure viral load.”

Currently, only remdesivir has been approved by the Food and Drug Administration for treating COVID-19, but convalescent plasma and neutralizing monoclonal antibodies have been granted emergency-use authorization.

In an accompanying editor’s note, Preeti N. Malani, MD, with the division of infectious diseases at the University of Michigan, Ann Arbor, and associate editor of JAMA, and Robert M. Golub, MD, deputy editor of JAMA, pointed out that these results differ from an earlier interim analysis of BLAZE-1 data.

A previous publication by Peter Chen, MD, with the department of medicine at Cedars Sinai Medical Center, Los Angeles, compared the three monotherapy groups (no combination group) with placebo, and in that study the 2,800-mg dose of bamlanivimab versus placebo achieved statistical significance for reduction in viral load from baseline at day 11, whereas the other two doses did not.

The editors explain that, in the study by Dr. Chen, “Follow-up for the placebo group was incomplete at the time of the database lock on Sept. 5, 2020. In the final analysis reported in the current article, the database was locked on Oct. 6, 2020, and the longer follow-up for the placebo group, which is now complete, resulted in changes in the primary outcome among that group.”

They concluded: “The comparison of the monotherapy groups against the final results for the placebo group led to changes in the effect sizes,” and the statistical significance of the 2,800-mg group was erased.

The editors pointed out that monoclonal antibodies are likely to benefit certain patients but definitive answers regarding which patients will benefit and under what circumstances will likely take more time than clinicians have to make decisions on treatment.

Meanwhile, as this news organization reported, the United States has spent $375 million on bamlanivimab and $450 million on Regeneron’s monoclonal antibody cocktail of casirivimab plus imdevimab, with the promise to spend billions more.

However, 80% of the 660,000 doses delivered by the two companies are still sitting on shelves, federal officials said in a press briefing last week, because of doubts about efficacy, lack of resources for infusion centers, and questions on reimbursement.

“While the world waits for widespread administration of effective vaccines and additional data on treatments, local efforts should work to improve testing access and turnaround time and reduce logistical barriers to ensure that monoclonal therapies can be provided to patients who are most likely to benefit,” Dr. Malani and Dr. Golub wrote.

This trial was sponsored and funded by Eli Lilly. Dr. Gottlieb disclosed personal fees and nonfinancial support (medication for another trial) from Gilead Sciences and serving on an advisory board for Sentinel. Several coauthors have financial ties to Eli Lilly. Dr. Malani reported serving on the National Institute of Allergy and Infectious Diseases COVID-19 Preventive Monoclonal Antibody data and safety monitoring board but was not compensated. Dr. Golub disclosed no relevant financial relationships.

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

A combination treatment of neutralizing monoclonal antibodies bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 at day 11 compared with placebo among nonhospitalized patients who had mild to moderate COVID-19, new data indicate.

However, bamlanivimab alone in three different single-infusion doses showed no significant reduction in viral load, compared with placebo, according to the phase 2/3 study by Robert L. Gottlieb, MD, PhD, of the Baylor University Medical Center and the Baylor Scott & White Research Institute, both in Dallas, and colleagues.

Findings from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) study were published online Jan. 21 in JAMA. The results represent findings through Oct. 6, 2020.

BLAZE-1 was funded by Eli Lilly, which makes both of the antispike neutralizing antibodies. The trial was conducted at 49 U.S. centers and included 613 outpatients who tested positive for SARS-CoV-2 and had one or more mild to moderate symptoms.

Patients were randomized to one of five groups (four treatment groups and a placebo control), and researchers analyzed between-group differences.

All four treatment arms suggest a trend toward reduction in viral load, which was the primary endpoint of the trial, but only the combination showed a statistically significant reduction.

The average age of patients was 44.7 years, 54.6% were female, 42.5% were Hispanic, and 67.1% had at least one risk factor for severe COVID-19 (aged ≥55 years, body mass index of at least 30, or relevant comorbidity such as hypertension).

Among secondary outcomes, there were no consistent differences between the monotherapy groups or the combination group versus placebo for the other measures of viral load or clinical symptom scores.

The proportion of patients who had COVID-19–related hospitalizations or ED visits was 5.8% (nine events) for placebo; 1.0% (one event) for the 700-mg group; 1.9% (two events) for 2,800 mg; 2.0% (two events) for 7,000 mg; and 0.9% (one event) for combination treatment.

“Combining these two neutralizing monoclonal antibodies in clinical use may enhance viral load reduction and decrease treatment-emergent resistant variants,” the authors concluded.
 

Safety profile comparison

As for adverse events, immediate hypersensitivity reactions were reported in nine patients (six bamlanivimab, two combination treatment, and one placebo). No deaths occurred during the study.

Serious adverse events unrelated to SARS-CoV-2 infection or considered related to the study drug occurred in 0% (0/309) of patients in the bamlanivimab monotherapy groups; in 0.9% (1/112) of patients in the combination group; and in 0.6% (1/156) of patients in the placebo group.

The serious adverse event in the combination group was a urinary tract infection deemed unrelated to the study drug, the authors wrote.

The two most frequently reported side effects were nausea (3.0% for the 700-mg group; 3.7% for the 2,800-mg group; 5.0% for the 7,000-mg group; 3.6% for the combination group; and 3.8% for the placebo group) and diarrhea (1.0%, 1.9%, 5.9%, 0.9%, and 4.5%, respectively).

The authors included in the study’s limitations that the primary endpoint at day 11 may have been too late to best detect treatment effects.

“All patients, including those who received placebo, demonstrated substantial viral reduction by day 11,” they noted. “An earlier time point like day 3 or day 7 could possibly have been more appropriate to measure viral load.”

Currently, only remdesivir has been approved by the Food and Drug Administration for treating COVID-19, but convalescent plasma and neutralizing monoclonal antibodies have been granted emergency-use authorization.

In an accompanying editor’s note, Preeti N. Malani, MD, with the division of infectious diseases at the University of Michigan, Ann Arbor, and associate editor of JAMA, and Robert M. Golub, MD, deputy editor of JAMA, pointed out that these results differ from an earlier interim analysis of BLAZE-1 data.

A previous publication by Peter Chen, MD, with the department of medicine at Cedars Sinai Medical Center, Los Angeles, compared the three monotherapy groups (no combination group) with placebo, and in that study the 2,800-mg dose of bamlanivimab versus placebo achieved statistical significance for reduction in viral load from baseline at day 11, whereas the other two doses did not.

The editors explain that, in the study by Dr. Chen, “Follow-up for the placebo group was incomplete at the time of the database lock on Sept. 5, 2020. In the final analysis reported in the current article, the database was locked on Oct. 6, 2020, and the longer follow-up for the placebo group, which is now complete, resulted in changes in the primary outcome among that group.”

They concluded: “The comparison of the monotherapy groups against the final results for the placebo group led to changes in the effect sizes,” and the statistical significance of the 2,800-mg group was erased.

The editors pointed out that monoclonal antibodies are likely to benefit certain patients but definitive answers regarding which patients will benefit and under what circumstances will likely take more time than clinicians have to make decisions on treatment.

Meanwhile, as this news organization reported, the United States has spent $375 million on bamlanivimab and $450 million on Regeneron’s monoclonal antibody cocktail of casirivimab plus imdevimab, with the promise to spend billions more.

However, 80% of the 660,000 doses delivered by the two companies are still sitting on shelves, federal officials said in a press briefing last week, because of doubts about efficacy, lack of resources for infusion centers, and questions on reimbursement.

“While the world waits for widespread administration of effective vaccines and additional data on treatments, local efforts should work to improve testing access and turnaround time and reduce logistical barriers to ensure that monoclonal therapies can be provided to patients who are most likely to benefit,” Dr. Malani and Dr. Golub wrote.

This trial was sponsored and funded by Eli Lilly. Dr. Gottlieb disclosed personal fees and nonfinancial support (medication for another trial) from Gilead Sciences and serving on an advisory board for Sentinel. Several coauthors have financial ties to Eli Lilly. Dr. Malani reported serving on the National Institute of Allergy and Infectious Diseases COVID-19 Preventive Monoclonal Antibody data and safety monitoring board but was not compensated. Dr. Golub disclosed no relevant financial relationships.

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

Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.

Mohammed Haneefa Nizamudeen/Getty Images

Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.

In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.

To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.

Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.

Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.

The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.

The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).

Lack of statin use

The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.

The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.

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

Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.

Mohammed Haneefa Nizamudeen/Getty Images

Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.

In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.

To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.

Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.

Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.

The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.

The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).

Lack of statin use

The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.

The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.

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

Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.

Mohammed Haneefa Nizamudeen/Getty Images

Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.

In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.

To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.

Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.

Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.

The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.

The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).

Lack of statin use

The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.

The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.

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

Patients with a rare type of Alzheimer’s disease do not show the memory loss characteristic of the condition even over the long term, new research suggests. They also show some differences in neuropathology to typical patients with Alzheimer’s disease, raising hopes of discovering novel mechanisms that might protect against memory loss in typical forms of the disease.

“We are discovering that Alzheimer’s disease has more than one form. While the typical patient with Alzheimer’s disease will have impaired memory, patients with primary progressive aphasia linked to Alzheimer’s disease are quite different. They have problems with language – they know what they want to say but can’t find the words – but their memory is intact,” said lead author Marsel Mesulam, MD.

“We have found that these patients still show the same levels of neurofibrillary tangles which destroy neurons in the memory part of the brain as typical patients with Alzheimer’s disease, but in patients with primary progressive aphasia Alzheimer’s the nondominant side of this part of the brain showed less atrophy,” added Dr. Mesulam, who is director of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease at Northwestern University, Chicago. “It appears that these patients are more resilient to the effects of the neurofibrillary tangles.”

The researchers also found that two biomarkers that are established risk factors in typical Alzheimer’s disease do not appear to be risk factors for the primary progressive aphasia (PPA) form of the condition.

“These observations suggest that there are mechanisms that may protect the brain from Alzheimer’s-type damage. Studying these patients with this primary progressive aphasia form of Alzheimer’s disease may give us clues as to where to look for these mechanisms that may lead to new treatments for the memory loss associated with typical Alzheimer’s disease,” Dr. Mesulam commented.

The study was published online in the Jan. 13 issue of Neurology.

PPA is diagnosed when language impairment emerges on a background of preserved memory and behavior, with about 40% of cases representing atypical manifestations of Alzheimer’s disease, the researchers explained.

“While we knew that the memories of people with primary progressive aphasia were not affected at first, we did not know if they maintained their memory functioning over years,” Dr. Mesulam noted.

The current study aimed to investigate whether the memory preservation in PPA linked to Alzheimer’s disease is a consistent core feature or a transient finding confined to initial presentation, and to explore the underlying pathology of the condition.

The researchers searched their database to identify patients with PPA with autopsy or biomarker evidence of Alzheimer’s disease, who also had at least two consecutive visits during which language and memory assessment had been obtained with the same tests. The study included 17 patients with the PPA-type Alzheimer’s disease who compared with 14 patients who had typical Alzheimer’s disease with memory loss.

The authors pointed out that characterization of memory in patients with PPA is challenging because most tests use word lists, and thus patients may fail the test because of their language impairments. To address this issue, they included patients with PPA who had undergone memory tests involving recalling pictures of common objects.

Patients with typical Alzheimer’s disease underwent similar tests but used a list of common words.

A second round of tests was conducted in the primary progressive aphasia group an average of 2.4 years later and in the typical Alzheimer’s disease group an average of 1.7 years later.

Brain scans were also available for the patients with PPA, as well as postmortem evaluations for eight of the PPA cases and all the typical Alzheimer’s disease cases.

Results showed that patients with PPA had no decline in their memory skills when they took the tests a second time. At that point, they had been showing symptoms of the disorder for an average of 6 years. In contrast, their language skills declined significantly during the same period. For typical patients with Alzheimer’s disease, verbal memory and language skills declined with equal severity during the study.

Postmortem results showed that the two groups had comparable degrees of Alzheimer’s disease pathology in the medial temporal lobe – the main area of the brain affected in dementia.

However, MRI scans showed that patients with PPA had an asymmetrical atrophy of the dominant (left) hemisphere with sparing of the right sided medial temporal lobe, indicating a lack of neurodegeneration in the nondominant hemisphere, despite the presence of Alzheimer’s disease pathology.

It was also found that the patients with PPA had significantly lower prevalence of two factors strongly linked to Alzheimer’s disease – TDP-43 pathology and APOE ε4 positivity – than the typical patients with Alzheimer’s disease.

The authors concluded that “primary progressive aphasia Alzheimer’s syndrome offers unique opportunities for exploring the biological foundations of these phenomena that interactively modulate the impact of Alzheimer’s disease neuropathology on cognitive function.”
 

‘Preservation of cognition is the holy grail’

In an accompanying editorial, Seyed Ahmad Sajjadi, MD, University of California, Irvine; Sharon Ash, PhD, University of Pennsylvania, Philadelphia; and Stefano Cappa, MD, University School for Advanced Studies, Pavia, Italy, said these findings have important implications, “as ultimately, preservation of cognition is the holy grail of research in this area.”

They pointed out that the current observations imply “an uncoupling of neurodegeneration and pathology” in patients with PPA-type Alzheimer’s disease, adding that “it seems reasonable to conclude that neurodegeneration, and not mere presence of pathology, is what correlates with clinical presentation in these patients.”

The editorialists noted that the study has some limitations: the sample size is relatively small, not all patients with PPA-type Alzheimer’s disease underwent autopsy, MRI was only available for the aphasia group, and the two groups had different memory tests for comparison of their recognition memory.

But they concluded that this study “provides important insights about the potential reasons for differential vulnerability of the neural substrate of memory in those with different clinical presentations of Alzheimer’s disease pathology.”

The study was supported by the National Institute on Deafness and Communication Disorders, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the Davee Foundation, and the Jeanine Jones Fund.

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

Patients with a rare type of Alzheimer’s disease do not show the memory loss characteristic of the condition even over the long term, new research suggests. They also show some differences in neuropathology to typical patients with Alzheimer’s disease, raising hopes of discovering novel mechanisms that might protect against memory loss in typical forms of the disease.

“We are discovering that Alzheimer’s disease has more than one form. While the typical patient with Alzheimer’s disease will have impaired memory, patients with primary progressive aphasia linked to Alzheimer’s disease are quite different. They have problems with language – they know what they want to say but can’t find the words – but their memory is intact,” said lead author Marsel Mesulam, MD.

“We have found that these patients still show the same levels of neurofibrillary tangles which destroy neurons in the memory part of the brain as typical patients with Alzheimer’s disease, but in patients with primary progressive aphasia Alzheimer’s the nondominant side of this part of the brain showed less atrophy,” added Dr. Mesulam, who is director of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease at Northwestern University, Chicago. “It appears that these patients are more resilient to the effects of the neurofibrillary tangles.”

The researchers also found that two biomarkers that are established risk factors in typical Alzheimer’s disease do not appear to be risk factors for the primary progressive aphasia (PPA) form of the condition.

“These observations suggest that there are mechanisms that may protect the brain from Alzheimer’s-type damage. Studying these patients with this primary progressive aphasia form of Alzheimer’s disease may give us clues as to where to look for these mechanisms that may lead to new treatments for the memory loss associated with typical Alzheimer’s disease,” Dr. Mesulam commented.

The study was published online in the Jan. 13 issue of Neurology.

PPA is diagnosed when language impairment emerges on a background of preserved memory and behavior, with about 40% of cases representing atypical manifestations of Alzheimer’s disease, the researchers explained.

“While we knew that the memories of people with primary progressive aphasia were not affected at first, we did not know if they maintained their memory functioning over years,” Dr. Mesulam noted.

The current study aimed to investigate whether the memory preservation in PPA linked to Alzheimer’s disease is a consistent core feature or a transient finding confined to initial presentation, and to explore the underlying pathology of the condition.

The researchers searched their database to identify patients with PPA with autopsy or biomarker evidence of Alzheimer’s disease, who also had at least two consecutive visits during which language and memory assessment had been obtained with the same tests. The study included 17 patients with the PPA-type Alzheimer’s disease who compared with 14 patients who had typical Alzheimer’s disease with memory loss.

The authors pointed out that characterization of memory in patients with PPA is challenging because most tests use word lists, and thus patients may fail the test because of their language impairments. To address this issue, they included patients with PPA who had undergone memory tests involving recalling pictures of common objects.

Patients with typical Alzheimer’s disease underwent similar tests but used a list of common words.

A second round of tests was conducted in the primary progressive aphasia group an average of 2.4 years later and in the typical Alzheimer’s disease group an average of 1.7 years later.

Brain scans were also available for the patients with PPA, as well as postmortem evaluations for eight of the PPA cases and all the typical Alzheimer’s disease cases.

Results showed that patients with PPA had no decline in their memory skills when they took the tests a second time. At that point, they had been showing symptoms of the disorder for an average of 6 years. In contrast, their language skills declined significantly during the same period. For typical patients with Alzheimer’s disease, verbal memory and language skills declined with equal severity during the study.

Postmortem results showed that the two groups had comparable degrees of Alzheimer’s disease pathology in the medial temporal lobe – the main area of the brain affected in dementia.

However, MRI scans showed that patients with PPA had an asymmetrical atrophy of the dominant (left) hemisphere with sparing of the right sided medial temporal lobe, indicating a lack of neurodegeneration in the nondominant hemisphere, despite the presence of Alzheimer’s disease pathology.

It was also found that the patients with PPA had significantly lower prevalence of two factors strongly linked to Alzheimer’s disease – TDP-43 pathology and APOE ε4 positivity – than the typical patients with Alzheimer’s disease.

The authors concluded that “primary progressive aphasia Alzheimer’s syndrome offers unique opportunities for exploring the biological foundations of these phenomena that interactively modulate the impact of Alzheimer’s disease neuropathology on cognitive function.”
 

‘Preservation of cognition is the holy grail’

In an accompanying editorial, Seyed Ahmad Sajjadi, MD, University of California, Irvine; Sharon Ash, PhD, University of Pennsylvania, Philadelphia; and Stefano Cappa, MD, University School for Advanced Studies, Pavia, Italy, said these findings have important implications, “as ultimately, preservation of cognition is the holy grail of research in this area.”

They pointed out that the current observations imply “an uncoupling of neurodegeneration and pathology” in patients with PPA-type Alzheimer’s disease, adding that “it seems reasonable to conclude that neurodegeneration, and not mere presence of pathology, is what correlates with clinical presentation in these patients.”

The editorialists noted that the study has some limitations: the sample size is relatively small, not all patients with PPA-type Alzheimer’s disease underwent autopsy, MRI was only available for the aphasia group, and the two groups had different memory tests for comparison of their recognition memory.

But they concluded that this study “provides important insights about the potential reasons for differential vulnerability of the neural substrate of memory in those with different clinical presentations of Alzheimer’s disease pathology.”

The study was supported by the National Institute on Deafness and Communication Disorders, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the Davee Foundation, and the Jeanine Jones Fund.

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

Patients with a rare type of Alzheimer’s disease do not show the memory loss characteristic of the condition even over the long term, new research suggests. They also show some differences in neuropathology to typical patients with Alzheimer’s disease, raising hopes of discovering novel mechanisms that might protect against memory loss in typical forms of the disease.

“We are discovering that Alzheimer’s disease has more than one form. While the typical patient with Alzheimer’s disease will have impaired memory, patients with primary progressive aphasia linked to Alzheimer’s disease are quite different. They have problems with language – they know what they want to say but can’t find the words – but their memory is intact,” said lead author Marsel Mesulam, MD.

“We have found that these patients still show the same levels of neurofibrillary tangles which destroy neurons in the memory part of the brain as typical patients with Alzheimer’s disease, but in patients with primary progressive aphasia Alzheimer’s the nondominant side of this part of the brain showed less atrophy,” added Dr. Mesulam, who is director of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease at Northwestern University, Chicago. “It appears that these patients are more resilient to the effects of the neurofibrillary tangles.”

The researchers also found that two biomarkers that are established risk factors in typical Alzheimer’s disease do not appear to be risk factors for the primary progressive aphasia (PPA) form of the condition.

“These observations suggest that there are mechanisms that may protect the brain from Alzheimer’s-type damage. Studying these patients with this primary progressive aphasia form of Alzheimer’s disease may give us clues as to where to look for these mechanisms that may lead to new treatments for the memory loss associated with typical Alzheimer’s disease,” Dr. Mesulam commented.

The study was published online in the Jan. 13 issue of Neurology.

PPA is diagnosed when language impairment emerges on a background of preserved memory and behavior, with about 40% of cases representing atypical manifestations of Alzheimer’s disease, the researchers explained.

“While we knew that the memories of people with primary progressive aphasia were not affected at first, we did not know if they maintained their memory functioning over years,” Dr. Mesulam noted.

The current study aimed to investigate whether the memory preservation in PPA linked to Alzheimer’s disease is a consistent core feature or a transient finding confined to initial presentation, and to explore the underlying pathology of the condition.

The researchers searched their database to identify patients with PPA with autopsy or biomarker evidence of Alzheimer’s disease, who also had at least two consecutive visits during which language and memory assessment had been obtained with the same tests. The study included 17 patients with the PPA-type Alzheimer’s disease who compared with 14 patients who had typical Alzheimer’s disease with memory loss.

The authors pointed out that characterization of memory in patients with PPA is challenging because most tests use word lists, and thus patients may fail the test because of their language impairments. To address this issue, they included patients with PPA who had undergone memory tests involving recalling pictures of common objects.

Patients with typical Alzheimer’s disease underwent similar tests but used a list of common words.

A second round of tests was conducted in the primary progressive aphasia group an average of 2.4 years later and in the typical Alzheimer’s disease group an average of 1.7 years later.

Brain scans were also available for the patients with PPA, as well as postmortem evaluations for eight of the PPA cases and all the typical Alzheimer’s disease cases.

Results showed that patients with PPA had no decline in their memory skills when they took the tests a second time. At that point, they had been showing symptoms of the disorder for an average of 6 years. In contrast, their language skills declined significantly during the same period. For typical patients with Alzheimer’s disease, verbal memory and language skills declined with equal severity during the study.

Postmortem results showed that the two groups had comparable degrees of Alzheimer’s disease pathology in the medial temporal lobe – the main area of the brain affected in dementia.

However, MRI scans showed that patients with PPA had an asymmetrical atrophy of the dominant (left) hemisphere with sparing of the right sided medial temporal lobe, indicating a lack of neurodegeneration in the nondominant hemisphere, despite the presence of Alzheimer’s disease pathology.

It was also found that the patients with PPA had significantly lower prevalence of two factors strongly linked to Alzheimer’s disease – TDP-43 pathology and APOE ε4 positivity – than the typical patients with Alzheimer’s disease.

The authors concluded that “primary progressive aphasia Alzheimer’s syndrome offers unique opportunities for exploring the biological foundations of these phenomena that interactively modulate the impact of Alzheimer’s disease neuropathology on cognitive function.”
 

‘Preservation of cognition is the holy grail’

In an accompanying editorial, Seyed Ahmad Sajjadi, MD, University of California, Irvine; Sharon Ash, PhD, University of Pennsylvania, Philadelphia; and Stefano Cappa, MD, University School for Advanced Studies, Pavia, Italy, said these findings have important implications, “as ultimately, preservation of cognition is the holy grail of research in this area.”

They pointed out that the current observations imply “an uncoupling of neurodegeneration and pathology” in patients with PPA-type Alzheimer’s disease, adding that “it seems reasonable to conclude that neurodegeneration, and not mere presence of pathology, is what correlates with clinical presentation in these patients.”

The editorialists noted that the study has some limitations: the sample size is relatively small, not all patients with PPA-type Alzheimer’s disease underwent autopsy, MRI was only available for the aphasia group, and the two groups had different memory tests for comparison of their recognition memory.

But they concluded that this study “provides important insights about the potential reasons for differential vulnerability of the neural substrate of memory in those with different clinical presentations of Alzheimer’s disease pathology.”

The study was supported by the National Institute on Deafness and Communication Disorders, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the Davee Foundation, and the Jeanine Jones Fund.

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

A distinguished international panel of acne experts has identified major gaps in current clinical practice guidelines for the management of acne.

“The challenge with acne guidelines is they mainly focus on facial acne and they’re informed by randomized controlled trials which are conducted over a relatively short period of time. Given that acne is a chronic disease, this actually produces a lack of clarity on multiple issues, including things like truncal acne, treatment escalation and de-escalation, maintenance therapy, patient perspective, and longitudinal management,” Alison Layton, MBChB, said in presenting the findings of the Personalizing Acne: Consensus of Experts (PACE) panel at the virtual annual congress of the European Academy of Dermatology and Venereology.

The PACE panel highlighted two key unmet needs in acne care as the dearth of guidance on how to implement patient-centered management in clinical practice, and the absence of high-quality evidence on how best to handle long-term maintenance therapy: When to initiate it, the best regimens, and when to escalate, switch, or de-escalate it, added Dr. Layton, a dermatologist at Hull York Medical School, Heslington, England, and associate medical director for research and development at Harrogate and District National Health Service Foundation Trust.

Most of the 13 dermatologists on the PACE panel were coauthors of the current U.S., European, or Canadian acne guidelines, so they are closely familiar with the guidelines’ strengths and shortcomings. For example, the American contingent includes Linda Stein Gold, MD, Detroit; Hilary E. Baldwin, MD, New Brunswick, NJ; Julie C. Harper, MD, Birmingham, Ala.; and Jonathan S. Weiss, MD, of Georgia, all members of the work group that created the current American Academy of Dermatology guidelines.

Strong points of the current guidelines are the high-quality, evidence-based recommendations on initial treatment of facial acne. However, a major weakness of existing guidelines is reflected in the fact that well over 40% of patients relapse after acne therapy, and these relapses can significantly impair quality of life and productivity, said Dr. Layton, one of several PACE panelists who coauthored the current European Dermatology Forum acne guidelines.

The PACE panel utilized a modified Delphi approach to reach consensus on their recommendations. Ten panelists rated current practice guidelines as “somewhat useful” for informing long-term management, two dermatologists deemed existing guidelines “not at all useful” in this regard, and one declined to answer the question.

“None of us felt the guidelines were very useful,” Dr. Layton noted.

It will take time, money, and research commitment to generate compelling data on best practices for long-term maintenance therapy for acne. Other areas in sore need of high-quality studies to improve the evidence-based care of acne include the appropriate length of antibiotic therapy for acne and how to effectively combine topical agents with oral antibiotics to support appropriate use of antimicrobials. In the meantime, the PACE group plans to issue interim practical consensus recommendations to beef up existing guidelines.

With regard to practical recommendations to improve patient-centered care, there was strong consensus among the panelists that acne management in certain patient subgroups requires special attention. These subgroups include patients with darker skin phototypes, heavy exercisers, transgender patients and patients with hormonal conditions, pregnant or breast-feeding women, patients with psychiatric issues, and children under age 10.

PACE panelists agreed that a physician-patient discussion about long-term treatment expectations is “paramount” to effective patient-centered management.

“To ensure a positive consultation experience, physicians should prioritize discussion of efficacy expectations, including timelines and treatment duration,” Dr. Layton continued.

Other key topics to address in promoting patient-centered management of acne include discussion of medication adverse effects and tolerability, application technique for topical treatments, the importance of adherence, and recommendations regarding a daily skin care routine, according to the PACE group.

Dr. Layton reported serving as a consultant to Galderma, which funded the PACE project, as well as half a dozen other pharmaceutical companies.

[email protected]

A distinguished international panel of acne experts has identified major gaps in current clinical practice guidelines for the management of acne.

“The challenge with acne guidelines is they mainly focus on facial acne and they’re informed by randomized controlled trials which are conducted over a relatively short period of time. Given that acne is a chronic disease, this actually produces a lack of clarity on multiple issues, including things like truncal acne, treatment escalation and de-escalation, maintenance therapy, patient perspective, and longitudinal management,” Alison Layton, MBChB, said in presenting the findings of the Personalizing Acne: Consensus of Experts (PACE) panel at the virtual annual congress of the European Academy of Dermatology and Venereology.

The PACE panel highlighted two key unmet needs in acne care as the dearth of guidance on how to implement patient-centered management in clinical practice, and the absence of high-quality evidence on how best to handle long-term maintenance therapy: When to initiate it, the best regimens, and when to escalate, switch, or de-escalate it, added Dr. Layton, a dermatologist at Hull York Medical School, Heslington, England, and associate medical director for research and development at Harrogate and District National Health Service Foundation Trust.

Most of the 13 dermatologists on the PACE panel were coauthors of the current U.S., European, or Canadian acne guidelines, so they are closely familiar with the guidelines’ strengths and shortcomings. For example, the American contingent includes Linda Stein Gold, MD, Detroit; Hilary E. Baldwin, MD, New Brunswick, NJ; Julie C. Harper, MD, Birmingham, Ala.; and Jonathan S. Weiss, MD, of Georgia, all members of the work group that created the current American Academy of Dermatology guidelines.

Strong points of the current guidelines are the high-quality, evidence-based recommendations on initial treatment of facial acne. However, a major weakness of existing guidelines is reflected in the fact that well over 40% of patients relapse after acne therapy, and these relapses can significantly impair quality of life and productivity, said Dr. Layton, one of several PACE panelists who coauthored the current European Dermatology Forum acne guidelines.

The PACE panel utilized a modified Delphi approach to reach consensus on their recommendations. Ten panelists rated current practice guidelines as “somewhat useful” for informing long-term management, two dermatologists deemed existing guidelines “not at all useful” in this regard, and one declined to answer the question.

“None of us felt the guidelines were very useful,” Dr. Layton noted.

It will take time, money, and research commitment to generate compelling data on best practices for long-term maintenance therapy for acne. Other areas in sore need of high-quality studies to improve the evidence-based care of acne include the appropriate length of antibiotic therapy for acne and how to effectively combine topical agents with oral antibiotics to support appropriate use of antimicrobials. In the meantime, the PACE group plans to issue interim practical consensus recommendations to beef up existing guidelines.

With regard to practical recommendations to improve patient-centered care, there was strong consensus among the panelists that acne management in certain patient subgroups requires special attention. These subgroups include patients with darker skin phototypes, heavy exercisers, transgender patients and patients with hormonal conditions, pregnant or breast-feeding women, patients with psychiatric issues, and children under age 10.

PACE panelists agreed that a physician-patient discussion about long-term treatment expectations is “paramount” to effective patient-centered management.

“To ensure a positive consultation experience, physicians should prioritize discussion of efficacy expectations, including timelines and treatment duration,” Dr. Layton continued.

Other key topics to address in promoting patient-centered management of acne include discussion of medication adverse effects and tolerability, application technique for topical treatments, the importance of adherence, and recommendations regarding a daily skin care routine, according to the PACE group.

Dr. Layton reported serving as a consultant to Galderma, which funded the PACE project, as well as half a dozen other pharmaceutical companies.

[email protected]

A distinguished international panel of acne experts has identified major gaps in current clinical practice guidelines for the management of acne.

“The challenge with acne guidelines is they mainly focus on facial acne and they’re informed by randomized controlled trials which are conducted over a relatively short period of time. Given that acne is a chronic disease, this actually produces a lack of clarity on multiple issues, including things like truncal acne, treatment escalation and de-escalation, maintenance therapy, patient perspective, and longitudinal management,” Alison Layton, MBChB, said in presenting the findings of the Personalizing Acne: Consensus of Experts (PACE) panel at the virtual annual congress of the European Academy of Dermatology and Venereology.

The PACE panel highlighted two key unmet needs in acne care as the dearth of guidance on how to implement patient-centered management in clinical practice, and the absence of high-quality evidence on how best to handle long-term maintenance therapy: When to initiate it, the best regimens, and when to escalate, switch, or de-escalate it, added Dr. Layton, a dermatologist at Hull York Medical School, Heslington, England, and associate medical director for research and development at Harrogate and District National Health Service Foundation Trust.

Most of the 13 dermatologists on the PACE panel were coauthors of the current U.S., European, or Canadian acne guidelines, so they are closely familiar with the guidelines’ strengths and shortcomings. For example, the American contingent includes Linda Stein Gold, MD, Detroit; Hilary E. Baldwin, MD, New Brunswick, NJ; Julie C. Harper, MD, Birmingham, Ala.; and Jonathan S. Weiss, MD, of Georgia, all members of the work group that created the current American Academy of Dermatology guidelines.

Strong points of the current guidelines are the high-quality, evidence-based recommendations on initial treatment of facial acne. However, a major weakness of existing guidelines is reflected in the fact that well over 40% of patients relapse after acne therapy, and these relapses can significantly impair quality of life and productivity, said Dr. Layton, one of several PACE panelists who coauthored the current European Dermatology Forum acne guidelines.

The PACE panel utilized a modified Delphi approach to reach consensus on their recommendations. Ten panelists rated current practice guidelines as “somewhat useful” for informing long-term management, two dermatologists deemed existing guidelines “not at all useful” in this regard, and one declined to answer the question.

“None of us felt the guidelines were very useful,” Dr. Layton noted.

It will take time, money, and research commitment to generate compelling data on best practices for long-term maintenance therapy for acne. Other areas in sore need of high-quality studies to improve the evidence-based care of acne include the appropriate length of antibiotic therapy for acne and how to effectively combine topical agents with oral antibiotics to support appropriate use of antimicrobials. In the meantime, the PACE group plans to issue interim practical consensus recommendations to beef up existing guidelines.

With regard to practical recommendations to improve patient-centered care, there was strong consensus among the panelists that acne management in certain patient subgroups requires special attention. These subgroups include patients with darker skin phototypes, heavy exercisers, transgender patients and patients with hormonal conditions, pregnant or breast-feeding women, patients with psychiatric issues, and children under age 10.

PACE panelists agreed that a physician-patient discussion about long-term treatment expectations is “paramount” to effective patient-centered management.

“To ensure a positive consultation experience, physicians should prioritize discussion of efficacy expectations, including timelines and treatment duration,” Dr. Layton continued.

Other key topics to address in promoting patient-centered management of acne include discussion of medication adverse effects and tolerability, application technique for topical treatments, the importance of adherence, and recommendations regarding a daily skin care routine, according to the PACE group.

Dr. Layton reported serving as a consultant to Galderma, which funded the PACE project, as well as half a dozen other pharmaceutical companies.

[email protected]