Neurology Reviews

Cluster headache attacks induced by either pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) or vasoactive intestinal polypeptide (VIP) do not lead to changes in plasma levels of calcitonin gene-related peptide (CGRP) or markers of mast cell activation such as tryptase and histamine, a new study has found.

“Whether cluster headache attacks provoked by CGRP and PACAP38/VIP are mediated by distinct signaling pathways will be worth investigating in forthcoming studies,” wrote Lanfranco Pellesi, MD, of the Danish Headache Center at the University of Copenhagen, and his coauthors. The study was published in Cephalalgia.

To assess how these biochemical variables might contribute to cluster headache attacks, the researchers launched a randomized, double-blind trial of data from 44 Danish participants with cluster headache. The average age of the patients was 38 years; 14 had active episodic cluster headache, 15 had episodic cluster headache in remission, and 15 had chronic cluster headache.

All patients received a continuous infusion of either PACAP38 (10 pmol/kg per minute) or VIP (8 pmol/kg per minute) over a 20-minute period, using a time- and volume-controlled infusion pump. Blood was collected for analysis at fixed time points, including at baseline, at the end of the infusion, 10 minutes after the infusion, and 70 minutes after the infusion. Technical problems led to missing values in 285 out of 1,144 planned plasma samples.

PACAP38 infusion resulted in a cluster headache attack in 13 of the 44 participants and VIP induced an attack in 12 of the 44. No differences in plasma CGRP (P = .7074), tryptase (P = .6673), and histamine (P = .4792) levels were found between patients who developed attacks and those who did not, and the plasma concentrations did not differ among the various blood-drawing time points.

There was also no difference in plasma CGRP levels between patients with active episodic cluster headache, those with episodic cluster headache in remission, and those with chronic cluster headache. After post hoc analysis, plasma tryptase and plasma histamine levels were similar among the three cluster headache patient groups.

The final link to the cluster headache puzzle has not yet been found

“We know a lot about cluster headache: how it presents, how we can stop it acutely, and how we can stop it preventively. But we don’t know everything about all the neurotransmitters involved, the triggers that start an attack, or the causes of pain,” Alan Rapoport, MD, professor of neurology at the University of California, Los Angeles (UCLA), and past president of the International Headache Society, said in an interview. “This study was performed to find the answer to a small piece of the puzzle. Is CGRP the missing link for patients who begin a cluster attack, or should we be looking elsewhere?

“I would be cautious and say it appears that it doesn’t seem to be related, but further studies may show something different,” he added. “The reason for my qualification: There is a monoclonal antibody [galcanezumab], which grabs CGRP and prevents it from docking on its receptor, that has been approved for preventive treatment of episodic cluster headache. When you have episodic cluster, go into a cluster period, and take galcanezumab, it could and should decrease the number of attacks that you would ordinarily have had. That means it is related somewhat. But it certainly doesn’t work for everyone, so more investigations like this are needed.”

“What’s important about this study is that it opens up the possibility that there is another way into the cluster attack that could be operationalized for therapeutic purposes,” Peter Goadsby, MD, PhD, professor of neurology at UCLA and president of the American Headache Society, said in an interview.

When asked about the authors’ stated interest in investigating “if monoclonal antibodies targeting the CGRP pathway prevent PACAP38- or VIP-induced cluster headache attacks” as a follow-up, Dr. Goadsby strongly backed the idea. “If I sound excited about actually exploring whether that was a useful treatment or not, it’s because cluster headache is a dreadful condition. And the sooner you could work out whether it was useful or put the money into something else, well, that’s where I’d go.

“I think the principle here of doing experimental medicine, getting into human work with targets like this at the earliest possible time, is something that is not done as often as would be appropriate,” he added. “There is not enough investment, in my view, in early phase experimental work, which really just gets to that next step. Broadly speaking, the encouragement and support of experimental medicine is crucial to developing new therapies.”

The authors recognized their study’s potential limitations, including it’s being an exploratory study with results that should be interpreted cautiously. They acknowledged discrepancies with previous studies of plasma CGRP during cluster headache attacks, offering “different methodologies, including intra-assay differences and the location of blood sampling” as a possible reason. They also explained that some of the data are missing “completely at random” due to their policy of discarding all observations with incomplete laboratory measurements, adding that the impact on their sample size was “only modest.”

“In spite of these limitations,” Dr. Rapoport said, “this is an excellent study that shows us that PACAP38- and VIP-induced cluster headache attacks are not associated with alterations in plasma CGRP or in histamine and tryptase.”

Regarding potential conflicts of interest, one author reported being employed at the testing lab where the histamine measurements were conducted, as did another author who serves as the lab’s scientific adviser. A third author reported receiving personal fees from various pharmaceutical companies.

Cluster headache attacks induced by either pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) or vasoactive intestinal polypeptide (VIP) do not lead to changes in plasma levels of calcitonin gene-related peptide (CGRP) or markers of mast cell activation such as tryptase and histamine, a new study has found.

“Whether cluster headache attacks provoked by CGRP and PACAP38/VIP are mediated by distinct signaling pathways will be worth investigating in forthcoming studies,” wrote Lanfranco Pellesi, MD, of the Danish Headache Center at the University of Copenhagen, and his coauthors. The study was published in Cephalalgia.

To assess how these biochemical variables might contribute to cluster headache attacks, the researchers launched a randomized, double-blind trial of data from 44 Danish participants with cluster headache. The average age of the patients was 38 years; 14 had active episodic cluster headache, 15 had episodic cluster headache in remission, and 15 had chronic cluster headache.

All patients received a continuous infusion of either PACAP38 (10 pmol/kg per minute) or VIP (8 pmol/kg per minute) over a 20-minute period, using a time- and volume-controlled infusion pump. Blood was collected for analysis at fixed time points, including at baseline, at the end of the infusion, 10 minutes after the infusion, and 70 minutes after the infusion. Technical problems led to missing values in 285 out of 1,144 planned plasma samples.

PACAP38 infusion resulted in a cluster headache attack in 13 of the 44 participants and VIP induced an attack in 12 of the 44. No differences in plasma CGRP (P = .7074), tryptase (P = .6673), and histamine (P = .4792) levels were found between patients who developed attacks and those who did not, and the plasma concentrations did not differ among the various blood-drawing time points.

There was also no difference in plasma CGRP levels between patients with active episodic cluster headache, those with episodic cluster headache in remission, and those with chronic cluster headache. After post hoc analysis, plasma tryptase and plasma histamine levels were similar among the three cluster headache patient groups.

The final link to the cluster headache puzzle has not yet been found

“We know a lot about cluster headache: how it presents, how we can stop it acutely, and how we can stop it preventively. But we don’t know everything about all the neurotransmitters involved, the triggers that start an attack, or the causes of pain,” Alan Rapoport, MD, professor of neurology at the University of California, Los Angeles (UCLA), and past president of the International Headache Society, said in an interview. “This study was performed to find the answer to a small piece of the puzzle. Is CGRP the missing link for patients who begin a cluster attack, or should we be looking elsewhere?

“I would be cautious and say it appears that it doesn’t seem to be related, but further studies may show something different,” he added. “The reason for my qualification: There is a monoclonal antibody [galcanezumab], which grabs CGRP and prevents it from docking on its receptor, that has been approved for preventive treatment of episodic cluster headache. When you have episodic cluster, go into a cluster period, and take galcanezumab, it could and should decrease the number of attacks that you would ordinarily have had. That means it is related somewhat. But it certainly doesn’t work for everyone, so more investigations like this are needed.”

“What’s important about this study is that it opens up the possibility that there is another way into the cluster attack that could be operationalized for therapeutic purposes,” Peter Goadsby, MD, PhD, professor of neurology at UCLA and president of the American Headache Society, said in an interview.

When asked about the authors’ stated interest in investigating “if monoclonal antibodies targeting the CGRP pathway prevent PACAP38- or VIP-induced cluster headache attacks” as a follow-up, Dr. Goadsby strongly backed the idea. “If I sound excited about actually exploring whether that was a useful treatment or not, it’s because cluster headache is a dreadful condition. And the sooner you could work out whether it was useful or put the money into something else, well, that’s where I’d go.

“I think the principle here of doing experimental medicine, getting into human work with targets like this at the earliest possible time, is something that is not done as often as would be appropriate,” he added. “There is not enough investment, in my view, in early phase experimental work, which really just gets to that next step. Broadly speaking, the encouragement and support of experimental medicine is crucial to developing new therapies.”

The authors recognized their study’s potential limitations, including it’s being an exploratory study with results that should be interpreted cautiously. They acknowledged discrepancies with previous studies of plasma CGRP during cluster headache attacks, offering “different methodologies, including intra-assay differences and the location of blood sampling” as a possible reason. They also explained that some of the data are missing “completely at random” due to their policy of discarding all observations with incomplete laboratory measurements, adding that the impact on their sample size was “only modest.”

“In spite of these limitations,” Dr. Rapoport said, “this is an excellent study that shows us that PACAP38- and VIP-induced cluster headache attacks are not associated with alterations in plasma CGRP or in histamine and tryptase.”

Regarding potential conflicts of interest, one author reported being employed at the testing lab where the histamine measurements were conducted, as did another author who serves as the lab’s scientific adviser. A third author reported receiving personal fees from various pharmaceutical companies.

Cluster headache attacks induced by either pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) or vasoactive intestinal polypeptide (VIP) do not lead to changes in plasma levels of calcitonin gene-related peptide (CGRP) or markers of mast cell activation such as tryptase and histamine, a new study has found.

“Whether cluster headache attacks provoked by CGRP and PACAP38/VIP are mediated by distinct signaling pathways will be worth investigating in forthcoming studies,” wrote Lanfranco Pellesi, MD, of the Danish Headache Center at the University of Copenhagen, and his coauthors. The study was published in Cephalalgia.

To assess how these biochemical variables might contribute to cluster headache attacks, the researchers launched a randomized, double-blind trial of data from 44 Danish participants with cluster headache. The average age of the patients was 38 years; 14 had active episodic cluster headache, 15 had episodic cluster headache in remission, and 15 had chronic cluster headache.

All patients received a continuous infusion of either PACAP38 (10 pmol/kg per minute) or VIP (8 pmol/kg per minute) over a 20-minute period, using a time- and volume-controlled infusion pump. Blood was collected for analysis at fixed time points, including at baseline, at the end of the infusion, 10 minutes after the infusion, and 70 minutes after the infusion. Technical problems led to missing values in 285 out of 1,144 planned plasma samples.

PACAP38 infusion resulted in a cluster headache attack in 13 of the 44 participants and VIP induced an attack in 12 of the 44. No differences in plasma CGRP (P = .7074), tryptase (P = .6673), and histamine (P = .4792) levels were found between patients who developed attacks and those who did not, and the plasma concentrations did not differ among the various blood-drawing time points.

There was also no difference in plasma CGRP levels between patients with active episodic cluster headache, those with episodic cluster headache in remission, and those with chronic cluster headache. After post hoc analysis, plasma tryptase and plasma histamine levels were similar among the three cluster headache patient groups.

The final link to the cluster headache puzzle has not yet been found

“We know a lot about cluster headache: how it presents, how we can stop it acutely, and how we can stop it preventively. But we don’t know everything about all the neurotransmitters involved, the triggers that start an attack, or the causes of pain,” Alan Rapoport, MD, professor of neurology at the University of California, Los Angeles (UCLA), and past president of the International Headache Society, said in an interview. “This study was performed to find the answer to a small piece of the puzzle. Is CGRP the missing link for patients who begin a cluster attack, or should we be looking elsewhere?

“I would be cautious and say it appears that it doesn’t seem to be related, but further studies may show something different,” he added. “The reason for my qualification: There is a monoclonal antibody [galcanezumab], which grabs CGRP and prevents it from docking on its receptor, that has been approved for preventive treatment of episodic cluster headache. When you have episodic cluster, go into a cluster period, and take galcanezumab, it could and should decrease the number of attacks that you would ordinarily have had. That means it is related somewhat. But it certainly doesn’t work for everyone, so more investigations like this are needed.”

“What’s important about this study is that it opens up the possibility that there is another way into the cluster attack that could be operationalized for therapeutic purposes,” Peter Goadsby, MD, PhD, professor of neurology at UCLA and president of the American Headache Society, said in an interview.

When asked about the authors’ stated interest in investigating “if monoclonal antibodies targeting the CGRP pathway prevent PACAP38- or VIP-induced cluster headache attacks” as a follow-up, Dr. Goadsby strongly backed the idea. “If I sound excited about actually exploring whether that was a useful treatment or not, it’s because cluster headache is a dreadful condition. And the sooner you could work out whether it was useful or put the money into something else, well, that’s where I’d go.

“I think the principle here of doing experimental medicine, getting into human work with targets like this at the earliest possible time, is something that is not done as often as would be appropriate,” he added. “There is not enough investment, in my view, in early phase experimental work, which really just gets to that next step. Broadly speaking, the encouragement and support of experimental medicine is crucial to developing new therapies.”

The authors recognized their study’s potential limitations, including it’s being an exploratory study with results that should be interpreted cautiously. They acknowledged discrepancies with previous studies of plasma CGRP during cluster headache attacks, offering “different methodologies, including intra-assay differences and the location of blood sampling” as a possible reason. They also explained that some of the data are missing “completely at random” due to their policy of discarding all observations with incomplete laboratory measurements, adding that the impact on their sample size was “only modest.”

“In spite of these limitations,” Dr. Rapoport said, “this is an excellent study that shows us that PACAP38- and VIP-induced cluster headache attacks are not associated with alterations in plasma CGRP or in histamine and tryptase.”

Regarding potential conflicts of interest, one author reported being employed at the testing lab where the histamine measurements were conducted, as did another author who serves as the lab’s scientific adviser. A third author reported receiving personal fees from various pharmaceutical companies.

All-cause mortality is significantly higher for individuals with autism spectrum disorder or attention-deficit/hyperactivity disorder than for the general population, based on data from more than 600,000 individuals.

Studies of individuals with mental disorders have suggested an increased mortality risk, compared with the general population, but similar studies of individuals with autism spectrum disorder (ASD) or ADHD have yielded inconsistent results, Ferrán Catalá-López, PhD, of the Institute of Health Carlos III, Madrid, and colleagues wrote.

In a systematic review and meta-analysis published in JAMA Pediatrics, the researchers examined 27 studies including 642,260 individuals; 154,238 with ASD and 396,488 with ADHD. The studies were published up to April 1, 2021, and included deaths from natural causes (such as respiratory illness or cancer) and unnatural (external) causes, such as accident, injury, or poisoning. The proportion of females in the studies ranged from 14% to 100%; the follow-up ranged from 3 to 33 years; and three studies included first-degree relatives.

Overall, all-cause mortality was significantly higher among individuals with ASD (rate ratio, 2.37) and ADHD (RR, 2.13), compared with the general population. Among individuals with ASD, deaths from natural causes and unnatural causes were significantly increased, compared with the general population (RR, 3.80 and RR, 2.50, respectively). Among individuals with ADHD, deaths from natural causes were not significantly increased (RR, 1.62), but deaths from unnatural causes were significantly increased, compared with the general population (RR, 2.81).

Potential mechanisms to explain the excess mortality among individuals with ASD and ADHD include health determinants and biological pathways, but the complex nature of the associations make the establishment of causality a challenge, the researchers wrote in their discussion of the findings. In general, “severe mental and behavioral disorders appear to be associated with reduced life expectancy, both in terms of mortality from external causes and mortality from other medical conditions or diseases.” With regard to ASD/ADHD in particular, these individuals often experience emotional and social problems as they enter adulthood. “Behaviors such as impulsivity and/or inattention can be contributing factors for injuries and unintentional incidents in children with ASD/ADHD,” they added.

The study findings were limited by several factors including the possible omission of studies and the use of study-level data rather than individual participant data, as well as the limitation of electronic health records, the researchers noted. Also, the studies were mostly conducted in Western countries and the results may not be generalizable to other countries.

Although ASD and ADHD were associated with a significant increased risk of all-cause mortality, “the results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks,” the researchers said. However, the results were strengthened by the large study sample, and offer a comprehensive look at the evidence supporting increased mortality risk among individuals with ASD or ADHD, and highlight the need to identify modifiable risk factors.

“Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health,” they said.
 

Recent research support associations

The study was important because ASD and ADHD may persist into adulthood, but data from previous epidemiological studies on the impact of these disorders on mortality are inconsistent, lead author Dr. Catalá-López said in an interview.

“We conducted a systematic review and meta-analysis to evaluate all available studies of mortality associations in people with these disorders, which provide the most updated and evidence-based approach,” he explained. “Our study has only become possible in the past few years because several large population-based epidemiological studies have been available reporting similar mortality-related outcomes.”

Dr. Catalá-López said that the study findings have value in clinical practice. “We found that people with autism or attention-deficit/hyperactivity disorders would have an increased risk of mortality when compared to the general population. In our opinion, understanding the causes and mechanisms of these associations can lead to specific strategies to prevent avoidable deaths.

“Autism and attention-hyperactivity/deficit disorder are problems that can be managed with adequate and concrete programs at an early age, and most premature deaths, at least deaths from unnatural causes, can be prevented,” Dr. Catalá-López said.

“Furthermore, we believe that these results may shed some light for future research. For example, more prospective studies would be needed, particularly to examine cause-specific mortality, in larger populations of children and youth with autism/attention-deficit/hyperactivity disorder, including some of the more common comorbidities,” Dr. Catalá-López added.
 

Findings support need for screening and prevention strategies

The clear message that individuals with ASD or ADHD often die of preventable or unnatural causes demands attention and “demands widespread recognition and the implementation of systematic screening and preventive approaches,” Russell A. Barkley, PhD, of Virginia Commonwealth University, Richmond, and Geraldine Dawson, PhD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

The studies included in the review also demonstrate that ADHD is associated with more than a twofold risk of early mortality in children and a more than a fourfold risk in mortality by age 45 years, they said.

The editorialists noted that the increased mortality risk may explain the ongoing conundrum among clinicians as to why the prevalence of ADHD seems to decline with age, “such that 5%-8% of children may meet diagnostic criteria for ADHD while that figure falls to 4%-5% of adults and 2%-3% of older adults,” despite evidence that a majority of childhood cases will be rediagnosed in adulthood. However, the current study offers an alternative. “This systematic review and meta-analysis and the studies included within it make plain that another explanation is the greater loss of individuals with these conditions from the population over time owing to heightened mortality, compared with typical peers,” they said.

“In addition to ADHD diagnosis, ASD diagnosis is also associated with other psychiatric comorbidities that are correlated with increased risk for mortality, including anxiety and affective disorders,” the editorialists noted. Other considerations for increased mortality among individuals with ASD include different protective and risk factors associated with suicide risk, compared with the general population, as well as poorer social and daily living skills compared to the general population.

The study findings “argue for individuals with ADHD and individuals with ASD being viewed through a public health lens with screening and prevention strategies offered beginning in early childhood. These findings should also give impetus to efforts to try to reduce the first order risk factors that are predisposing to reduced life expectancy, such as obesity, substance use, poor diet, poor sleep, and limited exercise among children and adults with ASD and ADHD,” they said.

“A preventive strategy would necessitate primary care physicians becoming more aware of the linkage between both ASD diagnosis and ADHD diagnosis and early mortality as well as their link to reduced [estimated life expectancy],” and such an approach could potentially reduce the higher mortality risk identified in the current review, they concluded.

Dr. Barkley reported speaking and other fees from Takeda, Medice Pharmaceutical, and AstraZeneca; book royalties from Guilford Publications and the American Psychological Association; and course royalties from ContiningEdCourses.net and Premier Educational Seminars. Dr. Dawson reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health during the submitted work and personal fees from Apple. Dr. Dawson also disclosed a patent for license to Apple, and Dr. Dawson and Duke University have benefited financially from technology and data that have been licensed to Apple. The study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Researchers including lead author Dr. Catalá-López received funding from sources including the Centro de Investigación Biomédica en Red de Salud Mental; one coauthor received support from an Australian Research Council Discovery Early Career Researcher Award, a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network, the Spanish Health Services Research on Chronic Patients Network, and Institute of Health Carlos III. The researchers had no financial conflicts to disclose.

All-cause mortality is significantly higher for individuals with autism spectrum disorder or attention-deficit/hyperactivity disorder than for the general population, based on data from more than 600,000 individuals.

Studies of individuals with mental disorders have suggested an increased mortality risk, compared with the general population, but similar studies of individuals with autism spectrum disorder (ASD) or ADHD have yielded inconsistent results, Ferrán Catalá-López, PhD, of the Institute of Health Carlos III, Madrid, and colleagues wrote.

In a systematic review and meta-analysis published in JAMA Pediatrics, the researchers examined 27 studies including 642,260 individuals; 154,238 with ASD and 396,488 with ADHD. The studies were published up to April 1, 2021, and included deaths from natural causes (such as respiratory illness or cancer) and unnatural (external) causes, such as accident, injury, or poisoning. The proportion of females in the studies ranged from 14% to 100%; the follow-up ranged from 3 to 33 years; and three studies included first-degree relatives.

Overall, all-cause mortality was significantly higher among individuals with ASD (rate ratio, 2.37) and ADHD (RR, 2.13), compared with the general population. Among individuals with ASD, deaths from natural causes and unnatural causes were significantly increased, compared with the general population (RR, 3.80 and RR, 2.50, respectively). Among individuals with ADHD, deaths from natural causes were not significantly increased (RR, 1.62), but deaths from unnatural causes were significantly increased, compared with the general population (RR, 2.81).

Potential mechanisms to explain the excess mortality among individuals with ASD and ADHD include health determinants and biological pathways, but the complex nature of the associations make the establishment of causality a challenge, the researchers wrote in their discussion of the findings. In general, “severe mental and behavioral disorders appear to be associated with reduced life expectancy, both in terms of mortality from external causes and mortality from other medical conditions or diseases.” With regard to ASD/ADHD in particular, these individuals often experience emotional and social problems as they enter adulthood. “Behaviors such as impulsivity and/or inattention can be contributing factors for injuries and unintentional incidents in children with ASD/ADHD,” they added.

The study findings were limited by several factors including the possible omission of studies and the use of study-level data rather than individual participant data, as well as the limitation of electronic health records, the researchers noted. Also, the studies were mostly conducted in Western countries and the results may not be generalizable to other countries.

Although ASD and ADHD were associated with a significant increased risk of all-cause mortality, “the results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks,” the researchers said. However, the results were strengthened by the large study sample, and offer a comprehensive look at the evidence supporting increased mortality risk among individuals with ASD or ADHD, and highlight the need to identify modifiable risk factors.

“Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health,” they said.
 

Recent research support associations

The study was important because ASD and ADHD may persist into adulthood, but data from previous epidemiological studies on the impact of these disorders on mortality are inconsistent, lead author Dr. Catalá-López said in an interview.

“We conducted a systematic review and meta-analysis to evaluate all available studies of mortality associations in people with these disorders, which provide the most updated and evidence-based approach,” he explained. “Our study has only become possible in the past few years because several large population-based epidemiological studies have been available reporting similar mortality-related outcomes.”

Dr. Catalá-López said that the study findings have value in clinical practice. “We found that people with autism or attention-deficit/hyperactivity disorders would have an increased risk of mortality when compared to the general population. In our opinion, understanding the causes and mechanisms of these associations can lead to specific strategies to prevent avoidable deaths.

“Autism and attention-hyperactivity/deficit disorder are problems that can be managed with adequate and concrete programs at an early age, and most premature deaths, at least deaths from unnatural causes, can be prevented,” Dr. Catalá-López said.

“Furthermore, we believe that these results may shed some light for future research. For example, more prospective studies would be needed, particularly to examine cause-specific mortality, in larger populations of children and youth with autism/attention-deficit/hyperactivity disorder, including some of the more common comorbidities,” Dr. Catalá-López added.
 

Findings support need for screening and prevention strategies

The clear message that individuals with ASD or ADHD often die of preventable or unnatural causes demands attention and “demands widespread recognition and the implementation of systematic screening and preventive approaches,” Russell A. Barkley, PhD, of Virginia Commonwealth University, Richmond, and Geraldine Dawson, PhD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

The studies included in the review also demonstrate that ADHD is associated with more than a twofold risk of early mortality in children and a more than a fourfold risk in mortality by age 45 years, they said.

The editorialists noted that the increased mortality risk may explain the ongoing conundrum among clinicians as to why the prevalence of ADHD seems to decline with age, “such that 5%-8% of children may meet diagnostic criteria for ADHD while that figure falls to 4%-5% of adults and 2%-3% of older adults,” despite evidence that a majority of childhood cases will be rediagnosed in adulthood. However, the current study offers an alternative. “This systematic review and meta-analysis and the studies included within it make plain that another explanation is the greater loss of individuals with these conditions from the population over time owing to heightened mortality, compared with typical peers,” they said.

“In addition to ADHD diagnosis, ASD diagnosis is also associated with other psychiatric comorbidities that are correlated with increased risk for mortality, including anxiety and affective disorders,” the editorialists noted. Other considerations for increased mortality among individuals with ASD include different protective and risk factors associated with suicide risk, compared with the general population, as well as poorer social and daily living skills compared to the general population.

The study findings “argue for individuals with ADHD and individuals with ASD being viewed through a public health lens with screening and prevention strategies offered beginning in early childhood. These findings should also give impetus to efforts to try to reduce the first order risk factors that are predisposing to reduced life expectancy, such as obesity, substance use, poor diet, poor sleep, and limited exercise among children and adults with ASD and ADHD,” they said.

“A preventive strategy would necessitate primary care physicians becoming more aware of the linkage between both ASD diagnosis and ADHD diagnosis and early mortality as well as their link to reduced [estimated life expectancy],” and such an approach could potentially reduce the higher mortality risk identified in the current review, they concluded.

Dr. Barkley reported speaking and other fees from Takeda, Medice Pharmaceutical, and AstraZeneca; book royalties from Guilford Publications and the American Psychological Association; and course royalties from ContiningEdCourses.net and Premier Educational Seminars. Dr. Dawson reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health during the submitted work and personal fees from Apple. Dr. Dawson also disclosed a patent for license to Apple, and Dr. Dawson and Duke University have benefited financially from technology and data that have been licensed to Apple. The study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Researchers including lead author Dr. Catalá-López received funding from sources including the Centro de Investigación Biomédica en Red de Salud Mental; one coauthor received support from an Australian Research Council Discovery Early Career Researcher Award, a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network, the Spanish Health Services Research on Chronic Patients Network, and Institute of Health Carlos III. The researchers had no financial conflicts to disclose.

All-cause mortality is significantly higher for individuals with autism spectrum disorder or attention-deficit/hyperactivity disorder than for the general population, based on data from more than 600,000 individuals.

Studies of individuals with mental disorders have suggested an increased mortality risk, compared with the general population, but similar studies of individuals with autism spectrum disorder (ASD) or ADHD have yielded inconsistent results, Ferrán Catalá-López, PhD, of the Institute of Health Carlos III, Madrid, and colleagues wrote.

In a systematic review and meta-analysis published in JAMA Pediatrics, the researchers examined 27 studies including 642,260 individuals; 154,238 with ASD and 396,488 with ADHD. The studies were published up to April 1, 2021, and included deaths from natural causes (such as respiratory illness or cancer) and unnatural (external) causes, such as accident, injury, or poisoning. The proportion of females in the studies ranged from 14% to 100%; the follow-up ranged from 3 to 33 years; and three studies included first-degree relatives.

Overall, all-cause mortality was significantly higher among individuals with ASD (rate ratio, 2.37) and ADHD (RR, 2.13), compared with the general population. Among individuals with ASD, deaths from natural causes and unnatural causes were significantly increased, compared with the general population (RR, 3.80 and RR, 2.50, respectively). Among individuals with ADHD, deaths from natural causes were not significantly increased (RR, 1.62), but deaths from unnatural causes were significantly increased, compared with the general population (RR, 2.81).

Potential mechanisms to explain the excess mortality among individuals with ASD and ADHD include health determinants and biological pathways, but the complex nature of the associations make the establishment of causality a challenge, the researchers wrote in their discussion of the findings. In general, “severe mental and behavioral disorders appear to be associated with reduced life expectancy, both in terms of mortality from external causes and mortality from other medical conditions or diseases.” With regard to ASD/ADHD in particular, these individuals often experience emotional and social problems as they enter adulthood. “Behaviors such as impulsivity and/or inattention can be contributing factors for injuries and unintentional incidents in children with ASD/ADHD,” they added.

The study findings were limited by several factors including the possible omission of studies and the use of study-level data rather than individual participant data, as well as the limitation of electronic health records, the researchers noted. Also, the studies were mostly conducted in Western countries and the results may not be generalizable to other countries.

Although ASD and ADHD were associated with a significant increased risk of all-cause mortality, “the results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks,” the researchers said. However, the results were strengthened by the large study sample, and offer a comprehensive look at the evidence supporting increased mortality risk among individuals with ASD or ADHD, and highlight the need to identify modifiable risk factors.

“Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health,” they said.
 

Recent research support associations

The study was important because ASD and ADHD may persist into adulthood, but data from previous epidemiological studies on the impact of these disorders on mortality are inconsistent, lead author Dr. Catalá-López said in an interview.

“We conducted a systematic review and meta-analysis to evaluate all available studies of mortality associations in people with these disorders, which provide the most updated and evidence-based approach,” he explained. “Our study has only become possible in the past few years because several large population-based epidemiological studies have been available reporting similar mortality-related outcomes.”

Dr. Catalá-López said that the study findings have value in clinical practice. “We found that people with autism or attention-deficit/hyperactivity disorders would have an increased risk of mortality when compared to the general population. In our opinion, understanding the causes and mechanisms of these associations can lead to specific strategies to prevent avoidable deaths.

“Autism and attention-hyperactivity/deficit disorder are problems that can be managed with adequate and concrete programs at an early age, and most premature deaths, at least deaths from unnatural causes, can be prevented,” Dr. Catalá-López said.

“Furthermore, we believe that these results may shed some light for future research. For example, more prospective studies would be needed, particularly to examine cause-specific mortality, in larger populations of children and youth with autism/attention-deficit/hyperactivity disorder, including some of the more common comorbidities,” Dr. Catalá-López added.
 

Findings support need for screening and prevention strategies

The clear message that individuals with ASD or ADHD often die of preventable or unnatural causes demands attention and “demands widespread recognition and the implementation of systematic screening and preventive approaches,” Russell A. Barkley, PhD, of Virginia Commonwealth University, Richmond, and Geraldine Dawson, PhD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

The studies included in the review also demonstrate that ADHD is associated with more than a twofold risk of early mortality in children and a more than a fourfold risk in mortality by age 45 years, they said.

The editorialists noted that the increased mortality risk may explain the ongoing conundrum among clinicians as to why the prevalence of ADHD seems to decline with age, “such that 5%-8% of children may meet diagnostic criteria for ADHD while that figure falls to 4%-5% of adults and 2%-3% of older adults,” despite evidence that a majority of childhood cases will be rediagnosed in adulthood. However, the current study offers an alternative. “This systematic review and meta-analysis and the studies included within it make plain that another explanation is the greater loss of individuals with these conditions from the population over time owing to heightened mortality, compared with typical peers,” they said.

“In addition to ADHD diagnosis, ASD diagnosis is also associated with other psychiatric comorbidities that are correlated with increased risk for mortality, including anxiety and affective disorders,” the editorialists noted. Other considerations for increased mortality among individuals with ASD include different protective and risk factors associated with suicide risk, compared with the general population, as well as poorer social and daily living skills compared to the general population.

The study findings “argue for individuals with ADHD and individuals with ASD being viewed through a public health lens with screening and prevention strategies offered beginning in early childhood. These findings should also give impetus to efforts to try to reduce the first order risk factors that are predisposing to reduced life expectancy, such as obesity, substance use, poor diet, poor sleep, and limited exercise among children and adults with ASD and ADHD,” they said.

“A preventive strategy would necessitate primary care physicians becoming more aware of the linkage between both ASD diagnosis and ADHD diagnosis and early mortality as well as their link to reduced [estimated life expectancy],” and such an approach could potentially reduce the higher mortality risk identified in the current review, they concluded.

Dr. Barkley reported speaking and other fees from Takeda, Medice Pharmaceutical, and AstraZeneca; book royalties from Guilford Publications and the American Psychological Association; and course royalties from ContiningEdCourses.net and Premier Educational Seminars. Dr. Dawson reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health during the submitted work and personal fees from Apple. Dr. Dawson also disclosed a patent for license to Apple, and Dr. Dawson and Duke University have benefited financially from technology and data that have been licensed to Apple. The study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Researchers including lead author Dr. Catalá-López received funding from sources including the Centro de Investigación Biomédica en Red de Salud Mental; one coauthor received support from an Australian Research Council Discovery Early Career Researcher Award, a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network, the Spanish Health Services Research on Chronic Patients Network, and Institute of Health Carlos III. The researchers had no financial conflicts to disclose.

I’m not fanatical about dragging stable patients in. If someone is doing fine, having them come in once a year is all I ask. They have better things to do, and I have patients who need my attention more.

Of course, there will always be those who abuse this. They try to drag it out to 18 months, sometimes 2 years. I don’t think having patients drop in for 10-15 minutes once a year to make sure they’re still alive is unreasonable, but maybe that’s just me. Admittedly, during the last 2 years I’ve kind of let it slide a bit, but I think everyone has.

Last week a lady I see for an annual check-in called to make an appointment. She’d been dodging my secretary’s reminders for a few months, so I cut her migraine refill from a 90-day supply to 30 days to encourage her. She called, made an appointment for the following morning, and asked that I send in a refill for 90 days because otherwise her insurance won’t cover it. So, trying to be nice, I did, figuring she was on the schedule now.

Of course, she didn’t show up the next morning. She didn’t cancel, or call in with “I’m sick” or “sorry, I spaced on it” or some other issue. She just no-showed. One of the many banes of outpatient medicine.

Normally I avoid looking at my patients’ online presence, but I got curious. This lady has often suggested I check out her social media account for financial and real estate tips. I never had, until that morning.

Her Twitter account for the last several days was full of reminders to her followers for an in-person seminar on real estate flipping that she was hosting, which, surprisingly, started at the exact time as her appointment with me was supposed to.

I’m pretty sure she ain’t that stupid. She knew exactly what she was doing, and never planned on keeping the appointment. Now she had a 90-day supply of meds and no incentive to follow up with me before then.

Certainly, it’s not the worst thing. The drug involved isn’t controlled, and in 24 years I’ve had patients do far worse.

But it still changes the trust factor in the medical relationship. She isn’t getting another 90-day refill without coming in, and if she has to pay cash for 30 days that’s her problem, not mine. She can avoid that by calling in to schedule before then. Though I doubt she will.

I try to work with my patients. I really do. Her behavior is rude and inconsiderate, but (at least to me) doesn’t cross the line to firing her from the practice.

But it does make it trickier to be her doctor, since I now know that she isn’t always truthful with me and my staff.

And that sort of thing is important in this field.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I’m not fanatical about dragging stable patients in. If someone is doing fine, having them come in once a year is all I ask. They have better things to do, and I have patients who need my attention more.

Of course, there will always be those who abuse this. They try to drag it out to 18 months, sometimes 2 years. I don’t think having patients drop in for 10-15 minutes once a year to make sure they’re still alive is unreasonable, but maybe that’s just me. Admittedly, during the last 2 years I’ve kind of let it slide a bit, but I think everyone has.

Last week a lady I see for an annual check-in called to make an appointment. She’d been dodging my secretary’s reminders for a few months, so I cut her migraine refill from a 90-day supply to 30 days to encourage her. She called, made an appointment for the following morning, and asked that I send in a refill for 90 days because otherwise her insurance won’t cover it. So, trying to be nice, I did, figuring she was on the schedule now.

Of course, she didn’t show up the next morning. She didn’t cancel, or call in with “I’m sick” or “sorry, I spaced on it” or some other issue. She just no-showed. One of the many banes of outpatient medicine.

Normally I avoid looking at my patients’ online presence, but I got curious. This lady has often suggested I check out her social media account for financial and real estate tips. I never had, until that morning.

Her Twitter account for the last several days was full of reminders to her followers for an in-person seminar on real estate flipping that she was hosting, which, surprisingly, started at the exact time as her appointment with me was supposed to.

I’m pretty sure she ain’t that stupid. She knew exactly what she was doing, and never planned on keeping the appointment. Now she had a 90-day supply of meds and no incentive to follow up with me before then.

Certainly, it’s not the worst thing. The drug involved isn’t controlled, and in 24 years I’ve had patients do far worse.

But it still changes the trust factor in the medical relationship. She isn’t getting another 90-day refill without coming in, and if she has to pay cash for 30 days that’s her problem, not mine. She can avoid that by calling in to schedule before then. Though I doubt she will.

I try to work with my patients. I really do. Her behavior is rude and inconsiderate, but (at least to me) doesn’t cross the line to firing her from the practice.

But it does make it trickier to be her doctor, since I now know that she isn’t always truthful with me and my staff.

And that sort of thing is important in this field.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I’m not fanatical about dragging stable patients in. If someone is doing fine, having them come in once a year is all I ask. They have better things to do, and I have patients who need my attention more.

Of course, there will always be those who abuse this. They try to drag it out to 18 months, sometimes 2 years. I don’t think having patients drop in for 10-15 minutes once a year to make sure they’re still alive is unreasonable, but maybe that’s just me. Admittedly, during the last 2 years I’ve kind of let it slide a bit, but I think everyone has.

Last week a lady I see for an annual check-in called to make an appointment. She’d been dodging my secretary’s reminders for a few months, so I cut her migraine refill from a 90-day supply to 30 days to encourage her. She called, made an appointment for the following morning, and asked that I send in a refill for 90 days because otherwise her insurance won’t cover it. So, trying to be nice, I did, figuring she was on the schedule now.

Of course, she didn’t show up the next morning. She didn’t cancel, or call in with “I’m sick” or “sorry, I spaced on it” or some other issue. She just no-showed. One of the many banes of outpatient medicine.

Normally I avoid looking at my patients’ online presence, but I got curious. This lady has often suggested I check out her social media account for financial and real estate tips. I never had, until that morning.

Her Twitter account for the last several days was full of reminders to her followers for an in-person seminar on real estate flipping that she was hosting, which, surprisingly, started at the exact time as her appointment with me was supposed to.

I’m pretty sure she ain’t that stupid. She knew exactly what she was doing, and never planned on keeping the appointment. Now she had a 90-day supply of meds and no incentive to follow up with me before then.

Certainly, it’s not the worst thing. The drug involved isn’t controlled, and in 24 years I’ve had patients do far worse.

But it still changes the trust factor in the medical relationship. She isn’t getting another 90-day refill without coming in, and if she has to pay cash for 30 days that’s her problem, not mine. She can avoid that by calling in to schedule before then. Though I doubt she will.

I try to work with my patients. I really do. Her behavior is rude and inconsiderate, but (at least to me) doesn’t cross the line to firing her from the practice.

But it does make it trickier to be her doctor, since I now know that she isn’t always truthful with me and my staff.

And that sort of thing is important in this field.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Sepsis is an alarmingly common cause behind ICU admissions in patients with multiple sclerosis (MS), a retrospective, population-based cohort study indicates.

Furthermore, it contributes to a disproportionately high percentage of the short-term mortality risk among patients with MS admitted to the ICU, findings also show. Short-term mortality risk was defined in the study as a combination of in-hospital death or discharge to hospice.

“We found that the risk of short-term mortality in critically ill patients with MS is four times higher among those with sepsis ... so sepsis appears to be comparatively more lethal among patients with MS than in the general population,” Lavi Oud, MD, professor of medicine, Texas Tech University HSC at the Permian Basin, Odessa, said in an email.

“[Although] the specific mechanisms underlying the markedly higher risk of sepsis among patients with MS compared to the general population remain to be fully elucidated ... it’s thought that the risk may stem from the dysfunction of the immune system in these patients related to MS itself and to the potentially adverse effect of the immunomodulating therapy we use in these patients,” he added.

The study was published online Jan. 11 in the Journal of Critical Care.
 

Sepsis rates

The Texas Inpatient Public Use Data File was used to identify adults with a diagnosis of MS admitted to the hospital between 2010 and 2017. Among the 19,837 patients with MS admitted to the ICU during the study interval, almost one-third (31.5%) had sepsis, investigators report. “The rate of sepsis among ICU admissions increased with age, ranging from 20.8% among those aged 18-44 to 39.4% among those aged 65 years or older,” investigators note.

The most common site of infection among MS patients admitted to the ICU were urinary in nature (65.2%), followed by respiratory (36.1%). A smaller proportion of infections (7.6%) involved the skin and soft tissues, researchers note. A full one-quarter of patients developed septic shock in response to their infection while the length of stay among patients with sepsis (mean of 10.9 days) was substantially longer than it was for those without sepsis (mean of 5.6 days), they observe.

At a mean total hospital cost of $121,797 for each ICU patient with sepsis, the cost of caring for each patient was nearly twofold higher than the mean total cost of taking care of ICU patients without sepsis (mean total cost, $65,179). On adjusted analysis, sepsis was associated with a 42.7% (95% confidence interval, 38.9-46.5; P < .0001) longer length of hospital stay and a 26.2% (95% CI, 23.1-29.1; P < .0001) higher total hospital cost compared with patients without sepsis, the authors point out.

Indeed, ICU admissions with sepsis accounted for 47.3% of all hospital days and for 46.1% of the aggregate hospital charges among all MS patients admitted to the ICU.

“The adjusted probability of short-term mortality was 13.4% (95% CI, 13.0-13.7) among ICU admissions with sepsis and 3.3% (95% CI, 3.2-3.4) among ICU admissions without sepsis,” the authors report.

This translated into a 44% higher risk of short-term mortality at an adjusted odds ratio of 1.44 (95% CI, 1.23-1.69; P < .0001) for those with sepsis, compared with those without, they add. Among all ICU admissions, sepsis was reported in over two-thirds of documented short-term mortality events. The risk of short-term mortality was also almost threefold higher among patients with sepsis who were age 65 years and older compared with patients aged 18-44. 

As Dr. Oud noted, there is no specific test for sepsis, and it can initially present in an atypical manner, especially in older, frailer, chronically ill patients as well as in patients with immune dysfunction. “Thus, considering sepsis as a possible cause of new deterioration in a patient’s condition is essential, along with the timely start of sepsis-related care,” Dr. Oud observed.

A limitation of the study was that the dataset did not include information on the type of MS a patient had, the duration of their illness, the treatment received, the level of disease activity, or the level of disability.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Sepsis is an alarmingly common cause behind ICU admissions in patients with multiple sclerosis (MS), a retrospective, population-based cohort study indicates.

Furthermore, it contributes to a disproportionately high percentage of the short-term mortality risk among patients with MS admitted to the ICU, findings also show. Short-term mortality risk was defined in the study as a combination of in-hospital death or discharge to hospice.

“We found that the risk of short-term mortality in critically ill patients with MS is four times higher among those with sepsis ... so sepsis appears to be comparatively more lethal among patients with MS than in the general population,” Lavi Oud, MD, professor of medicine, Texas Tech University HSC at the Permian Basin, Odessa, said in an email.

“[Although] the specific mechanisms underlying the markedly higher risk of sepsis among patients with MS compared to the general population remain to be fully elucidated ... it’s thought that the risk may stem from the dysfunction of the immune system in these patients related to MS itself and to the potentially adverse effect of the immunomodulating therapy we use in these patients,” he added.

The study was published online Jan. 11 in the Journal of Critical Care.
 

Sepsis rates

The Texas Inpatient Public Use Data File was used to identify adults with a diagnosis of MS admitted to the hospital between 2010 and 2017. Among the 19,837 patients with MS admitted to the ICU during the study interval, almost one-third (31.5%) had sepsis, investigators report. “The rate of sepsis among ICU admissions increased with age, ranging from 20.8% among those aged 18-44 to 39.4% among those aged 65 years or older,” investigators note.

The most common site of infection among MS patients admitted to the ICU were urinary in nature (65.2%), followed by respiratory (36.1%). A smaller proportion of infections (7.6%) involved the skin and soft tissues, researchers note. A full one-quarter of patients developed septic shock in response to their infection while the length of stay among patients with sepsis (mean of 10.9 days) was substantially longer than it was for those without sepsis (mean of 5.6 days), they observe.

At a mean total hospital cost of $121,797 for each ICU patient with sepsis, the cost of caring for each patient was nearly twofold higher than the mean total cost of taking care of ICU patients without sepsis (mean total cost, $65,179). On adjusted analysis, sepsis was associated with a 42.7% (95% confidence interval, 38.9-46.5; P < .0001) longer length of hospital stay and a 26.2% (95% CI, 23.1-29.1; P < .0001) higher total hospital cost compared with patients without sepsis, the authors point out.

Indeed, ICU admissions with sepsis accounted for 47.3% of all hospital days and for 46.1% of the aggregate hospital charges among all MS patients admitted to the ICU.

“The adjusted probability of short-term mortality was 13.4% (95% CI, 13.0-13.7) among ICU admissions with sepsis and 3.3% (95% CI, 3.2-3.4) among ICU admissions without sepsis,” the authors report.

This translated into a 44% higher risk of short-term mortality at an adjusted odds ratio of 1.44 (95% CI, 1.23-1.69; P < .0001) for those with sepsis, compared with those without, they add. Among all ICU admissions, sepsis was reported in over two-thirds of documented short-term mortality events. The risk of short-term mortality was also almost threefold higher among patients with sepsis who were age 65 years and older compared with patients aged 18-44. 

As Dr. Oud noted, there is no specific test for sepsis, and it can initially present in an atypical manner, especially in older, frailer, chronically ill patients as well as in patients with immune dysfunction. “Thus, considering sepsis as a possible cause of new deterioration in a patient’s condition is essential, along with the timely start of sepsis-related care,” Dr. Oud observed.

A limitation of the study was that the dataset did not include information on the type of MS a patient had, the duration of their illness, the treatment received, the level of disease activity, or the level of disability.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Sepsis is an alarmingly common cause behind ICU admissions in patients with multiple sclerosis (MS), a retrospective, population-based cohort study indicates.

Furthermore, it contributes to a disproportionately high percentage of the short-term mortality risk among patients with MS admitted to the ICU, findings also show. Short-term mortality risk was defined in the study as a combination of in-hospital death or discharge to hospice.

“We found that the risk of short-term mortality in critically ill patients with MS is four times higher among those with sepsis ... so sepsis appears to be comparatively more lethal among patients with MS than in the general population,” Lavi Oud, MD, professor of medicine, Texas Tech University HSC at the Permian Basin, Odessa, said in an email.

“[Although] the specific mechanisms underlying the markedly higher risk of sepsis among patients with MS compared to the general population remain to be fully elucidated ... it’s thought that the risk may stem from the dysfunction of the immune system in these patients related to MS itself and to the potentially adverse effect of the immunomodulating therapy we use in these patients,” he added.

The study was published online Jan. 11 in the Journal of Critical Care.
 

Sepsis rates

The Texas Inpatient Public Use Data File was used to identify adults with a diagnosis of MS admitted to the hospital between 2010 and 2017. Among the 19,837 patients with MS admitted to the ICU during the study interval, almost one-third (31.5%) had sepsis, investigators report. “The rate of sepsis among ICU admissions increased with age, ranging from 20.8% among those aged 18-44 to 39.4% among those aged 65 years or older,” investigators note.

The most common site of infection among MS patients admitted to the ICU were urinary in nature (65.2%), followed by respiratory (36.1%). A smaller proportion of infections (7.6%) involved the skin and soft tissues, researchers note. A full one-quarter of patients developed septic shock in response to their infection while the length of stay among patients with sepsis (mean of 10.9 days) was substantially longer than it was for those without sepsis (mean of 5.6 days), they observe.

At a mean total hospital cost of $121,797 for each ICU patient with sepsis, the cost of caring for each patient was nearly twofold higher than the mean total cost of taking care of ICU patients without sepsis (mean total cost, $65,179). On adjusted analysis, sepsis was associated with a 42.7% (95% confidence interval, 38.9-46.5; P < .0001) longer length of hospital stay and a 26.2% (95% CI, 23.1-29.1; P < .0001) higher total hospital cost compared with patients without sepsis, the authors point out.

Indeed, ICU admissions with sepsis accounted for 47.3% of all hospital days and for 46.1% of the aggregate hospital charges among all MS patients admitted to the ICU.

“The adjusted probability of short-term mortality was 13.4% (95% CI, 13.0-13.7) among ICU admissions with sepsis and 3.3% (95% CI, 3.2-3.4) among ICU admissions without sepsis,” the authors report.

This translated into a 44% higher risk of short-term mortality at an adjusted odds ratio of 1.44 (95% CI, 1.23-1.69; P < .0001) for those with sepsis, compared with those without, they add. Among all ICU admissions, sepsis was reported in over two-thirds of documented short-term mortality events. The risk of short-term mortality was also almost threefold higher among patients with sepsis who were age 65 years and older compared with patients aged 18-44. 

As Dr. Oud noted, there is no specific test for sepsis, and it can initially present in an atypical manner, especially in older, frailer, chronically ill patients as well as in patients with immune dysfunction. “Thus, considering sepsis as a possible cause of new deterioration in a patient’s condition is essential, along with the timely start of sepsis-related care,” Dr. Oud observed.

A limitation of the study was that the dataset did not include information on the type of MS a patient had, the duration of their illness, the treatment received, the level of disease activity, or the level of disability.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.

The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.

Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.

The study was published online Feb. 2 in Neurology.
 

Ongoing controversy

Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.

There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.

This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.

The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.

The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.

Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”

Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.

The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
 

More common in boys

Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.

The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.

They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.

At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.

During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.

Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.

However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).

This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.

Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
 

Other pathogens?

Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.

“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”

Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.

It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.

Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.

“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”

The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”

The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.

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

Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.

The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.

Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.

The study was published online Feb. 2 in Neurology.
 

Ongoing controversy

Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.

There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.

This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.

The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.

The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.

Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”

Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.

The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
 

More common in boys

Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.

The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.

They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.

At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.

During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.

Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.

However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).

This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.

Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
 

Other pathogens?

Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.

“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”

Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.

It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.

Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.

“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”

The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”

The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.

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

Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.

The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.

Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.

The study was published online Feb. 2 in Neurology.
 

Ongoing controversy

Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.

There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.

This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.

The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.

The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.

Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”

Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.

The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
 

More common in boys

Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.

The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.

They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.

At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.

During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.

Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.

However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).

This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.

Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
 

Other pathogens?

Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.

“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”

Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.

It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.

Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.

“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”

The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”

The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.

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

Individuals with restless legs syndrome showed an increase in symptom severity in the early phase of the COVID-19 pandemic in the United States in 2020, but this increase had waned by 2021, according to data from 500 participants in the National Restless Legs Syndrome Opioid Registry.

Sufferers of restless legs syndrome (RLS) experience not only sleep disturbance, but also daytime sleepiness, and high levels of depression, anxiety, and panic, wrote Benjamin Wipper of Harvard Medical School, Boston, and colleagues.

“Considering the link between RLS and psychiatric illness, it has been speculated that there may have been increases in RLS symptom severity alongside the recent rise in depression and anxiety,” but this association has not been explored, they said.

In a study published in Sleep Medicine , the researchers reviewed data from 500 adult participants in the National RLS Opioid Registry, a longitudinal observational study. Participants reported RLS symptom severity before and during the COVID-19 pandemic at 6-month intervals. Survey responses were collected from the early phase of the pandemic in the United States in January/February 2020, then in April/May 2020, and then 6 months later, from September 2020 through February 2021, and also 1 year later, in March 2021 through June 2021.

Participants completed a baseline phone interview and online survey, with symptoms assessed via the International Restless Legs Syndrome Study Group severity scale (IRLS), the Insomnia Severity Index (ISI), the General Anxiety Disorder-7 scale (GAD-7), and the Patient Health Questionnaire (PHQ-9).

In all, 153 participants completed surveys during January and February 2020, and 155 completed surveys during April and May 2020. Baseline characteristics were similar for all participants.

In a between-subjects analysis for these time periods, symptom scores on the IRLS were significantly higher in January/February 2020; participants were approximately twice as likely to have IRLS scores of 20 or higher compared to April/May 2020 (37.7% vs. 20.9%).

The researchers also compared responses by the same participants at baseline and 6 months later, from September 2020 through February 2021, and 1 year later, from March 2021 through June 2021. In this within-subjects analysis, 51.3% of the participants had increased IRLS scores in spring 2020. Participants were significantly more likely to have IRLS scores of 20 or above in the early COVID-19 period in April and May 2020 compared with baseline (37.7% vs. 26.6%). Both PHQ-9 and GAD-7 scores were higher during early COVID-19 in April and May 2020 than at baseline.

“Changes in IRLS were also significantly correlated with changes in both PHQ-9 and GAD-7 scores, providing further support for the associations of RLS to both depression and anxiety,” the researchers wrote. “Notably, individuals who completed surveys in January and February 2020 did not see increases in RLS severity or other mental health questionnaire values on subsequent six-month surveys completed during the pandemic or on the following iteration of surveys 1 year later. We suspect that these findings may be at least partially related to the timing of the surveys,” the researchers said. Six-month survey data for most patients were collected during a decline in cases and hospitalizations, and 1-year data in early 2021 may have reflected optimism with the availability of vaccines, they said. 

The study findings were limited by several factors including the observational design, which prevented conclusions about causality, and the lack of data on the effect of COVID-19 infection on RLS symptoms, which should be investigated in future studies, the researchers said.

However, the results are the first evidence of increased RLS symptom severity during the COVID-19 pandemic, and elevated scores were associated with sleep disturbance, depression, and anxiety, they wrote. “These data suggest that clinicians should attend to RLS symptoms during the current pandemic and in future instances of socioeconomic and/or political uncertainty. Future studies need to confirm these findings in other populations of patients with RLS,” they concluded.

The National RLS Opioid Registry has received research funding from the RLS Foundation, the Baszucki Brain Research Fund, Florence Petrlik Family Foundation, Diane and Richard Brainerd, Steven Silin, and Jerry Blakeley. The researchers had no financial conflicts to disclose.

Individuals with restless legs syndrome showed an increase in symptom severity in the early phase of the COVID-19 pandemic in the United States in 2020, but this increase had waned by 2021, according to data from 500 participants in the National Restless Legs Syndrome Opioid Registry.

Sufferers of restless legs syndrome (RLS) experience not only sleep disturbance, but also daytime sleepiness, and high levels of depression, anxiety, and panic, wrote Benjamin Wipper of Harvard Medical School, Boston, and colleagues.

“Considering the link between RLS and psychiatric illness, it has been speculated that there may have been increases in RLS symptom severity alongside the recent rise in depression and anxiety,” but this association has not been explored, they said.

In a study published in Sleep Medicine , the researchers reviewed data from 500 adult participants in the National RLS Opioid Registry, a longitudinal observational study. Participants reported RLS symptom severity before and during the COVID-19 pandemic at 6-month intervals. Survey responses were collected from the early phase of the pandemic in the United States in January/February 2020, then in April/May 2020, and then 6 months later, from September 2020 through February 2021, and also 1 year later, in March 2021 through June 2021.

Participants completed a baseline phone interview and online survey, with symptoms assessed via the International Restless Legs Syndrome Study Group severity scale (IRLS), the Insomnia Severity Index (ISI), the General Anxiety Disorder-7 scale (GAD-7), and the Patient Health Questionnaire (PHQ-9).

In all, 153 participants completed surveys during January and February 2020, and 155 completed surveys during April and May 2020. Baseline characteristics were similar for all participants.

In a between-subjects analysis for these time periods, symptom scores on the IRLS were significantly higher in January/February 2020; participants were approximately twice as likely to have IRLS scores of 20 or higher compared to April/May 2020 (37.7% vs. 20.9%).

The researchers also compared responses by the same participants at baseline and 6 months later, from September 2020 through February 2021, and 1 year later, from March 2021 through June 2021. In this within-subjects analysis, 51.3% of the participants had increased IRLS scores in spring 2020. Participants were significantly more likely to have IRLS scores of 20 or above in the early COVID-19 period in April and May 2020 compared with baseline (37.7% vs. 26.6%). Both PHQ-9 and GAD-7 scores were higher during early COVID-19 in April and May 2020 than at baseline.

“Changes in IRLS were also significantly correlated with changes in both PHQ-9 and GAD-7 scores, providing further support for the associations of RLS to both depression and anxiety,” the researchers wrote. “Notably, individuals who completed surveys in January and February 2020 did not see increases in RLS severity or other mental health questionnaire values on subsequent six-month surveys completed during the pandemic or on the following iteration of surveys 1 year later. We suspect that these findings may be at least partially related to the timing of the surveys,” the researchers said. Six-month survey data for most patients were collected during a decline in cases and hospitalizations, and 1-year data in early 2021 may have reflected optimism with the availability of vaccines, they said. 

The study findings were limited by several factors including the observational design, which prevented conclusions about causality, and the lack of data on the effect of COVID-19 infection on RLS symptoms, which should be investigated in future studies, the researchers said.

However, the results are the first evidence of increased RLS symptom severity during the COVID-19 pandemic, and elevated scores were associated with sleep disturbance, depression, and anxiety, they wrote. “These data suggest that clinicians should attend to RLS symptoms during the current pandemic and in future instances of socioeconomic and/or political uncertainty. Future studies need to confirm these findings in other populations of patients with RLS,” they concluded.

The National RLS Opioid Registry has received research funding from the RLS Foundation, the Baszucki Brain Research Fund, Florence Petrlik Family Foundation, Diane and Richard Brainerd, Steven Silin, and Jerry Blakeley. The researchers had no financial conflicts to disclose.

Individuals with restless legs syndrome showed an increase in symptom severity in the early phase of the COVID-19 pandemic in the United States in 2020, but this increase had waned by 2021, according to data from 500 participants in the National Restless Legs Syndrome Opioid Registry.

Sufferers of restless legs syndrome (RLS) experience not only sleep disturbance, but also daytime sleepiness, and high levels of depression, anxiety, and panic, wrote Benjamin Wipper of Harvard Medical School, Boston, and colleagues.

“Considering the link between RLS and psychiatric illness, it has been speculated that there may have been increases in RLS symptom severity alongside the recent rise in depression and anxiety,” but this association has not been explored, they said.

In a study published in Sleep Medicine , the researchers reviewed data from 500 adult participants in the National RLS Opioid Registry, a longitudinal observational study. Participants reported RLS symptom severity before and during the COVID-19 pandemic at 6-month intervals. Survey responses were collected from the early phase of the pandemic in the United States in January/February 2020, then in April/May 2020, and then 6 months later, from September 2020 through February 2021, and also 1 year later, in March 2021 through June 2021.

Participants completed a baseline phone interview and online survey, with symptoms assessed via the International Restless Legs Syndrome Study Group severity scale (IRLS), the Insomnia Severity Index (ISI), the General Anxiety Disorder-7 scale (GAD-7), and the Patient Health Questionnaire (PHQ-9).

In all, 153 participants completed surveys during January and February 2020, and 155 completed surveys during April and May 2020. Baseline characteristics were similar for all participants.

In a between-subjects analysis for these time periods, symptom scores on the IRLS were significantly higher in January/February 2020; participants were approximately twice as likely to have IRLS scores of 20 or higher compared to April/May 2020 (37.7% vs. 20.9%).

The researchers also compared responses by the same participants at baseline and 6 months later, from September 2020 through February 2021, and 1 year later, from March 2021 through June 2021. In this within-subjects analysis, 51.3% of the participants had increased IRLS scores in spring 2020. Participants were significantly more likely to have IRLS scores of 20 or above in the early COVID-19 period in April and May 2020 compared with baseline (37.7% vs. 26.6%). Both PHQ-9 and GAD-7 scores were higher during early COVID-19 in April and May 2020 than at baseline.

“Changes in IRLS were also significantly correlated with changes in both PHQ-9 and GAD-7 scores, providing further support for the associations of RLS to both depression and anxiety,” the researchers wrote. “Notably, individuals who completed surveys in January and February 2020 did not see increases in RLS severity or other mental health questionnaire values on subsequent six-month surveys completed during the pandemic or on the following iteration of surveys 1 year later. We suspect that these findings may be at least partially related to the timing of the surveys,” the researchers said. Six-month survey data for most patients were collected during a decline in cases and hospitalizations, and 1-year data in early 2021 may have reflected optimism with the availability of vaccines, they said. 

The study findings were limited by several factors including the observational design, which prevented conclusions about causality, and the lack of data on the effect of COVID-19 infection on RLS symptoms, which should be investigated in future studies, the researchers said.

However, the results are the first evidence of increased RLS symptom severity during the COVID-19 pandemic, and elevated scores were associated with sleep disturbance, depression, and anxiety, they wrote. “These data suggest that clinicians should attend to RLS symptoms during the current pandemic and in future instances of socioeconomic and/or political uncertainty. Future studies need to confirm these findings in other populations of patients with RLS,” they concluded.

The National RLS Opioid Registry has received research funding from the RLS Foundation, the Baszucki Brain Research Fund, Florence Petrlik Family Foundation, Diane and Richard Brainerd, Steven Silin, and Jerry Blakeley. The researchers had no financial conflicts to disclose.

Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.

Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.

High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.

SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.

The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.

No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.

Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.

Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.

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

Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.

Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.

High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.

SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.

The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.

No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.

Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.

Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.

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

Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.

Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.

High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.

SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.

The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.

No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.

Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.

Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.

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

The Centers for Disease Controls and Prevention has released a draft update of its current Clinical Practice Guidelines for Prescribing Opioids for pain management and is asking for public comment before moving forward.

The last guidance on this topic was released in 2016 and, among other things, noted that clinicians should be cautious when considering increasing dosage of opioids to 50 or more morphine milligram equivalents (MME)/day and should avoid increasing to a dose of 90 or more MME/day. It also noted that 3 days or less “will often be sufficient” regarding the quantity of lowest effective dose of immediate-release opioids to be prescribed for acute pain – and that more than 7 days “will rarely be needed.”

In the new report from the CDC’s National Center for Injury Prevention and Control (NCIPC), those dose limits have been replaced with the suggestion that clinicians use their best judgement – albeit still urging conservative use and even the possibility of nonopioid treatments.

The updated recommendations are now open for public comment via the Federal Register’s website through April 11.

“This comment period provides another critical opportunity for diverse audiences to offer their perspective on the draft clinical practice guideline,” Christopher M. Jones, PharmD, DrPH, acting director for the NCIPC, said in a release.

“We want to hear many voices from the public, including people living with pain and health care providers who help their patients manage pain,” Dr. Jones added.

Outpatient recommendations

The CDC noted that the updated guidance provides “evidence-based recommendations” for treatment of adults with acute, subacute, or chronic pain. It does not include guidance for managing pain related to sickle cell disease, cancer, or palliative care.

It is aimed at primary care clinicians and others who manage pain in an outpatient setting, including in dental and postsurgical practices and for those discharging patients from emergency departments. It does not apply to inpatient care.

The draft guidance includes 12 recommendations focused on four key areas:

• Helping clinicians determine whether or not to initiate opioid treatment for pain
• Opioid selection and dosage
• Duration of use and follow-up
• Assessing risk and addressing potential harms from use

The overall aim “is to ensure people have access to safe, accessible, and effective pain management that improves their function and quality of life while illuminating and reducing risks associated with prescription opioids and ultimately reducing the consequences of prescription opioid misuse and overdose,” the CDC notes.

In addition, the guidance itself “is intended to be a clinical tool to improve communication between providers and patients and empower them to make informed, patient-centered decisions,” the agency said in a press release.

It added that the new recommendations “are not intended to be applied as inflexible standards of care.” Rather, it is intended as a guide to support health care providers in their clinical decisionmaking as they provide individualized patient care.

Patients, caregivers, and providers are invited to submit comments over the next 60 days through the Federal Register docket.

“It is vitally important to CDC that we receive, process, and understand public feedback during the guideline update process,” the agency noted.

“The ultimate goal of this clinical practice guideline is to help people set and achieve personal goals to reduce their pain and improve their function and quality of life. Getting feedback from the public is essential to achieving this goal,” Dr. Jones said.

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

The Centers for Disease Controls and Prevention has released a draft update of its current Clinical Practice Guidelines for Prescribing Opioids for pain management and is asking for public comment before moving forward.

The last guidance on this topic was released in 2016 and, among other things, noted that clinicians should be cautious when considering increasing dosage of opioids to 50 or more morphine milligram equivalents (MME)/day and should avoid increasing to a dose of 90 or more MME/day. It also noted that 3 days or less “will often be sufficient” regarding the quantity of lowest effective dose of immediate-release opioids to be prescribed for acute pain – and that more than 7 days “will rarely be needed.”

In the new report from the CDC’s National Center for Injury Prevention and Control (NCIPC), those dose limits have been replaced with the suggestion that clinicians use their best judgement – albeit still urging conservative use and even the possibility of nonopioid treatments.

The updated recommendations are now open for public comment via the Federal Register’s website through April 11.

“This comment period provides another critical opportunity for diverse audiences to offer their perspective on the draft clinical practice guideline,” Christopher M. Jones, PharmD, DrPH, acting director for the NCIPC, said in a release.

“We want to hear many voices from the public, including people living with pain and health care providers who help their patients manage pain,” Dr. Jones added.

Outpatient recommendations

The CDC noted that the updated guidance provides “evidence-based recommendations” for treatment of adults with acute, subacute, or chronic pain. It does not include guidance for managing pain related to sickle cell disease, cancer, or palliative care.

It is aimed at primary care clinicians and others who manage pain in an outpatient setting, including in dental and postsurgical practices and for those discharging patients from emergency departments. It does not apply to inpatient care.

The draft guidance includes 12 recommendations focused on four key areas:

• Helping clinicians determine whether or not to initiate opioid treatment for pain
• Opioid selection and dosage
• Duration of use and follow-up
• Assessing risk and addressing potential harms from use

The overall aim “is to ensure people have access to safe, accessible, and effective pain management that improves their function and quality of life while illuminating and reducing risks associated with prescription opioids and ultimately reducing the consequences of prescription opioid misuse and overdose,” the CDC notes.

In addition, the guidance itself “is intended to be a clinical tool to improve communication between providers and patients and empower them to make informed, patient-centered decisions,” the agency said in a press release.

It added that the new recommendations “are not intended to be applied as inflexible standards of care.” Rather, it is intended as a guide to support health care providers in their clinical decisionmaking as they provide individualized patient care.

Patients, caregivers, and providers are invited to submit comments over the next 60 days through the Federal Register docket.

“It is vitally important to CDC that we receive, process, and understand public feedback during the guideline update process,” the agency noted.

“The ultimate goal of this clinical practice guideline is to help people set and achieve personal goals to reduce their pain and improve their function and quality of life. Getting feedback from the public is essential to achieving this goal,” Dr. Jones said.

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

The Centers for Disease Controls and Prevention has released a draft update of its current Clinical Practice Guidelines for Prescribing Opioids for pain management and is asking for public comment before moving forward.

The last guidance on this topic was released in 2016 and, among other things, noted that clinicians should be cautious when considering increasing dosage of opioids to 50 or more morphine milligram equivalents (MME)/day and should avoid increasing to a dose of 90 or more MME/day. It also noted that 3 days or less “will often be sufficient” regarding the quantity of lowest effective dose of immediate-release opioids to be prescribed for acute pain – and that more than 7 days “will rarely be needed.”

In the new report from the CDC’s National Center for Injury Prevention and Control (NCIPC), those dose limits have been replaced with the suggestion that clinicians use their best judgement – albeit still urging conservative use and even the possibility of nonopioid treatments.

The updated recommendations are now open for public comment via the Federal Register’s website through April 11.

“This comment period provides another critical opportunity for diverse audiences to offer their perspective on the draft clinical practice guideline,” Christopher M. Jones, PharmD, DrPH, acting director for the NCIPC, said in a release.

“We want to hear many voices from the public, including people living with pain and health care providers who help their patients manage pain,” Dr. Jones added.

Outpatient recommendations

The CDC noted that the updated guidance provides “evidence-based recommendations” for treatment of adults with acute, subacute, or chronic pain. It does not include guidance for managing pain related to sickle cell disease, cancer, or palliative care.

It is aimed at primary care clinicians and others who manage pain in an outpatient setting, including in dental and postsurgical practices and for those discharging patients from emergency departments. It does not apply to inpatient care.

The draft guidance includes 12 recommendations focused on four key areas:

• Helping clinicians determine whether or not to initiate opioid treatment for pain
• Opioid selection and dosage
• Duration of use and follow-up
• Assessing risk and addressing potential harms from use

The overall aim “is to ensure people have access to safe, accessible, and effective pain management that improves their function and quality of life while illuminating and reducing risks associated with prescription opioids and ultimately reducing the consequences of prescription opioid misuse and overdose,” the CDC notes.

In addition, the guidance itself “is intended to be a clinical tool to improve communication between providers and patients and empower them to make informed, patient-centered decisions,” the agency said in a press release.

It added that the new recommendations “are not intended to be applied as inflexible standards of care.” Rather, it is intended as a guide to support health care providers in their clinical decisionmaking as they provide individualized patient care.

Patients, caregivers, and providers are invited to submit comments over the next 60 days through the Federal Register docket.

“It is vitally important to CDC that we receive, process, and understand public feedback during the guideline update process,” the agency noted.

“The ultimate goal of this clinical practice guideline is to help people set and achieve personal goals to reduce their pain and improve their function and quality of life. Getting feedback from the public is essential to achieving this goal,” Dr. Jones said.

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

With the Omicron variant now accounting for almost 100% of COVID-19 cases in the United States, the 7-day average of daily COVID-related deaths hit 2,600 recently, the highest rate in about a year, the Washington Post reported.

That’s higher than the approximately 2,000 daily deaths in fall 2021 during the Delta surge, but less than the 3,000 daily deaths in January 2021, when COVID vaccines were not widely available, the Post’s data analysis said.

The Omicron variant generally causes less severe disease than other strains of COVID, but because it is so transmissible, Omicron is infecting higher raw numbers of people that previous strains.

“Even if on a per-case basis fewer people develop severe illness and die, when you apply a small percentage to a very large number, you get a substantial number,” Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins University, Baltimore, told the Post.

The unvaccinated, people over 75, and people with underlying medical conditions are the groups most endangered by Omicron, the Post said. About half of the deaths in January 2022 were among people over 75, compared with about a third in September 2021 during the Delta surge.

The age trend is seen in Florida, said Jason Salemi, PhD, an epidemiologist at the University of South Florida, Tampa. He told the Post that seniors accounted for about 85% of deaths in the winter of 2020-2021, about 60% during the Delta surge, and about 80% now during the Omicron surge.

The uptick in senior deaths may have occurred because seniors who got vaccinated in early 2021 didn’t get boosted ahead of the Omicron surge, he said.

“Omicron may be less severe for younger people, but it will still find vulnerable seniors in our community,” Dr. Salemi said. “That vaccination back in February isn’t as effective now if you aren’t boosted.”

CDC data shows that 95% of people in the United States over 65 have gotten at least one dose of vaccine, 88.5% are fully vaccinated, but only 62.5% have gotten a booster dose.

The COVID death rate is highest in the Midwest. During the last 2 months, Chicago reported more than 1,000 COVID deaths, almost as much as the December 2020 peak, The Post said. Minorities have been hit hard. About third of the city’s population is Black but about half the COVID victims are Black, the Post said.

“It’s been challenging because it goes up against the national narrative that omicron is nothing dangerous,” said Allison Arwady, commissioner of the Chicago Department of Public Health.

In a Feb. 9 news briefing at the White House, CDC Director Rochelle Walensky, MD, provided slightly different statistics on COVID-related deaths. She said that the 7-day average of daily deaths was about 2,400, up 3% from the previous week.

The 7-day daily average of cases is about 247,300 cases per day, down 44% from the previous week, she said. Hospital admissions are about 13,000 daily, down 25% from the previous week.

Dr. Walensky said the Omicron variant now accounts for almost 100% of COVID viruses circulating in the United States.

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

With the Omicron variant now accounting for almost 100% of COVID-19 cases in the United States, the 7-day average of daily COVID-related deaths hit 2,600 recently, the highest rate in about a year, the Washington Post reported.

That’s higher than the approximately 2,000 daily deaths in fall 2021 during the Delta surge, but less than the 3,000 daily deaths in January 2021, when COVID vaccines were not widely available, the Post’s data analysis said.

The Omicron variant generally causes less severe disease than other strains of COVID, but because it is so transmissible, Omicron is infecting higher raw numbers of people that previous strains.

“Even if on a per-case basis fewer people develop severe illness and die, when you apply a small percentage to a very large number, you get a substantial number,” Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins University, Baltimore, told the Post.

The unvaccinated, people over 75, and people with underlying medical conditions are the groups most endangered by Omicron, the Post said. About half of the deaths in January 2022 were among people over 75, compared with about a third in September 2021 during the Delta surge.

The age trend is seen in Florida, said Jason Salemi, PhD, an epidemiologist at the University of South Florida, Tampa. He told the Post that seniors accounted for about 85% of deaths in the winter of 2020-2021, about 60% during the Delta surge, and about 80% now during the Omicron surge.

The uptick in senior deaths may have occurred because seniors who got vaccinated in early 2021 didn’t get boosted ahead of the Omicron surge, he said.

“Omicron may be less severe for younger people, but it will still find vulnerable seniors in our community,” Dr. Salemi said. “That vaccination back in February isn’t as effective now if you aren’t boosted.”

CDC data shows that 95% of people in the United States over 65 have gotten at least one dose of vaccine, 88.5% are fully vaccinated, but only 62.5% have gotten a booster dose.

The COVID death rate is highest in the Midwest. During the last 2 months, Chicago reported more than 1,000 COVID deaths, almost as much as the December 2020 peak, The Post said. Minorities have been hit hard. About third of the city’s population is Black but about half the COVID victims are Black, the Post said.

“It’s been challenging because it goes up against the national narrative that omicron is nothing dangerous,” said Allison Arwady, commissioner of the Chicago Department of Public Health.

In a Feb. 9 news briefing at the White House, CDC Director Rochelle Walensky, MD, provided slightly different statistics on COVID-related deaths. She said that the 7-day average of daily deaths was about 2,400, up 3% from the previous week.

The 7-day daily average of cases is about 247,300 cases per day, down 44% from the previous week, she said. Hospital admissions are about 13,000 daily, down 25% from the previous week.

Dr. Walensky said the Omicron variant now accounts for almost 100% of COVID viruses circulating in the United States.

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

With the Omicron variant now accounting for almost 100% of COVID-19 cases in the United States, the 7-day average of daily COVID-related deaths hit 2,600 recently, the highest rate in about a year, the Washington Post reported.

That’s higher than the approximately 2,000 daily deaths in fall 2021 during the Delta surge, but less than the 3,000 daily deaths in January 2021, when COVID vaccines were not widely available, the Post’s data analysis said.

The Omicron variant generally causes less severe disease than other strains of COVID, but because it is so transmissible, Omicron is infecting higher raw numbers of people that previous strains.

“Even if on a per-case basis fewer people develop severe illness and die, when you apply a small percentage to a very large number, you get a substantial number,” Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins University, Baltimore, told the Post.

The unvaccinated, people over 75, and people with underlying medical conditions are the groups most endangered by Omicron, the Post said. About half of the deaths in January 2022 were among people over 75, compared with about a third in September 2021 during the Delta surge.

The age trend is seen in Florida, said Jason Salemi, PhD, an epidemiologist at the University of South Florida, Tampa. He told the Post that seniors accounted for about 85% of deaths in the winter of 2020-2021, about 60% during the Delta surge, and about 80% now during the Omicron surge.

The uptick in senior deaths may have occurred because seniors who got vaccinated in early 2021 didn’t get boosted ahead of the Omicron surge, he said.

“Omicron may be less severe for younger people, but it will still find vulnerable seniors in our community,” Dr. Salemi said. “That vaccination back in February isn’t as effective now if you aren’t boosted.”

CDC data shows that 95% of people in the United States over 65 have gotten at least one dose of vaccine, 88.5% are fully vaccinated, but only 62.5% have gotten a booster dose.

The COVID death rate is highest in the Midwest. During the last 2 months, Chicago reported more than 1,000 COVID deaths, almost as much as the December 2020 peak, The Post said. Minorities have been hit hard. About third of the city’s population is Black but about half the COVID victims are Black, the Post said.

“It’s been challenging because it goes up against the national narrative that omicron is nothing dangerous,” said Allison Arwady, commissioner of the Chicago Department of Public Health.

In a Feb. 9 news briefing at the White House, CDC Director Rochelle Walensky, MD, provided slightly different statistics on COVID-related deaths. She said that the 7-day average of daily deaths was about 2,400, up 3% from the previous week.

The 7-day daily average of cases is about 247,300 cases per day, down 44% from the previous week, she said. Hospital admissions are about 13,000 daily, down 25% from the previous week.

Dr. Walensky said the Omicron variant now accounts for almost 100% of COVID viruses circulating in the United States.

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