Children who do not get enough sleep for one night can be cranky, groggy, or meltdown prone the next day.

Over time, though, insufficient sleep may impair neurodevelopment in ways that can be measured on brain scans and tests long term, a new study shows.

Research published in The Lancet Child & Adolescent Health found that 9- and 10-year-olds who do not get at least 9 hours of sleep most nights tend to have less gray matter and smaller areas of the brain responsible for attention, memory, and inhibition control, relative to children who do get enough sleep.

The researchers also found a relationship between insufficient sleep and disrupted connections between the basal ganglia and cortical regions of the brain. These disruptions appeared to be linked to depression, thought problems, and impairments in crystallized intelligence, a type of intelligence that depends on memory.

The overall patterns persisted 2 years later, even as those who got enough sleep at baseline gradually slept less over time, while those who were not getting enough sleep to begin with continued to sleep about the same amount, the researchers reported.

The results bolster the case for delaying school start times, as California recently did, according one researcher who was not involved in the study.
 

The ABCD Study

To examine how insufficient sleep affects children’s mental health, cognition, brain function, and brain structure over 2 years, Ze Wang, PhD, professor of diagnostic radiology and nuclear medicine at the University of Maryland, Baltimore, and colleagues analyzed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study is tracking the biologic and behavioral development of more than 11,000 children in the United States who were recruited for the study when they were 9 or 10 years old.

For their new analysis, Dr. Wang’s group focused on 6,042 participants: 3,021 children with insufficient sleep who were matched with an equal number of participants who were similar in many respects, including sex, socioeconomic status, and puberty status, except they got at least 9 hours of sleep. They also looked at outcomes 2 years later from 749 of the matched pairs who had results available.

The investigators determined sleep duration based on how parents answered the question: “How many hours of sleep does your child get on most nights in the past 6 months?” Possible answers included at least 9 hours, 8-9 hours, 7-8 hours, 5-7 hours, or less than 5 hours. They also looked at functional and structural MRI scans, test results, and responses to questionnaires.

Negative effects of inadequate sleep were spread over “several different domains including brain structure, function, cognition, behavior, and mental health,” Dr. Wang said.

The strength of the relationship between sleep duration and the various outcomes was “modest” and based on group averages, he said. So, a given child who does not sleep for 9 hours most nights won’t necessarily perform worse than a child who gets enough sleep.

Still, modest effects may accumulate and have lasting consequences, Dr. Wang said.
 

Crystallized intelligence

The researchers looked at 42 behavioral outcomes, 32 of which were significantly different between the groups. Four outcomes in particular – depression, thought problems, performance on a picture-vocabulary test, and crystallized intelligence – were areas where insufficient sleep seemed to have a larger negative effect.

Sleep duration’s relationship with crystallized intelligence was twice that for fluid intelligence, which does not depend on memory.

“Sleep affects memory,” Dr. Wang said. “Crystallized intelligence depends on learned skills and knowledge, which are memory. In this sense, sleep is related to crystallized intelligence.”

One limitation of the study is that some parents may not accurately report how much sleep their child gets, Dr. Wang acknowledged. Children may be awake when parents think they are asleep, for example.

And although the results show getting 9 hours of sleep may help neurocognitive development, it’s also possible that excessive amounts of sleep could be problematic, the study authors wrote.

Further experiments are needed to prove that insufficient sleep – and not some other, unaccounted for factor – causes the observed impairments in neurodevelopment.

To promote healthy sleep, parents should keep a strict routine for their children, such as a regular bedtime and no electronic devices in the bedroom, Dr. Wang suggested. More physical activity during the day also should help.

If children have high levels of stress and depression, “finding the source is critical,” he said. Likewise, clinicians should consider how mental health can affect their patients’ sleep.
 

More to healthy sleep than duration

“This study both aligns with and advances existing research on the importance of sufficient sleep for child well-being,” said Ariel A. Williamson, PhD, DBSM, a psychologist and pediatric sleep expert in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia and assistant professor of psychiatry and pediatrics at University of Pennsylvania, also in Philadelphia.

The researchers used rigorous propensity score matching, longitudinal data, and brain imaging, which are “innovative methods that provide more evidence on potential mechanisms linking insufficient sleep and child outcomes,” said Dr. Williamson, who was not involved in the study.

While the investigators focused on sleep duration, child sleep health is multidimensional and includes other elements like timing and perception of sleep quality, Dr. Williamson noted. “For example, some research shows that having a sleep schedule that varies night to night is linked to poor child outcomes.”

Dr. Williamson tells families and clinicians that “sleep is a pillar of health,” equal to diet and exercise. That said, sleep recommendations need to fit within a family’s life – taking into account after school activities and late-night homework sessions. But extending sleep by just “20-30 minutes can make a meaningful difference for daytime functioning,” Dr. Williamson said.
 

Start school later?

Researchers have only relatively recently begun to understand how insufficient sleep affects adolescent neurocognitive development long term, and this study provides “crucial evidence” about the consequences, Lydia Gabriela Speyer, PhD, said in an editorial published with the study. Dr. Speyer is affiliated with the department of psychology at the University of Cambridge (England).

“Given the novel finding that insufficient sleep is associated with changes in brain structure and connectivity that are long-lasting, early intervention is crucial because such neural changes are probably not reversible and might consequently affect adolescents’ development into adulthood,” Dr. Speyer wrote.

Delaying school start times could be one way to help kids get more sleep. The American Academy of Pediatrics and the American Academy of Sleep Medicine recommend that middle schools and high schools start no earlier than 8:30 a.m. to better align with students’ circadian rhythm, Dr. Speyer noted.

As it is in the United States, most schools start closer to 8 a.m. In California, though, a law that went into effect on July 1 prohibits high schools from starting before 8:30 a.m. Other states are weighing similar legislation.

The research was supported by the National Institutes of Health. Dr. Wang and his coauthors and Dr. Speyer had no conflict of interest disclosures. Dr. Williamson is a sleep expert for the Pediatric Sleep Council (www.babysleep.com), which provides free information about early childhood sleep, but she does not receive compensation for this role.
 

Children who do not get enough sleep for one night can be cranky, groggy, or meltdown prone the next day.

Over time, though, insufficient sleep may impair neurodevelopment in ways that can be measured on brain scans and tests long term, a new study shows.

Research published in The Lancet Child & Adolescent Health found that 9- and 10-year-olds who do not get at least 9 hours of sleep most nights tend to have less gray matter and smaller areas of the brain responsible for attention, memory, and inhibition control, relative to children who do get enough sleep.

The researchers also found a relationship between insufficient sleep and disrupted connections between the basal ganglia and cortical regions of the brain. These disruptions appeared to be linked to depression, thought problems, and impairments in crystallized intelligence, a type of intelligence that depends on memory.

The overall patterns persisted 2 years later, even as those who got enough sleep at baseline gradually slept less over time, while those who were not getting enough sleep to begin with continued to sleep about the same amount, the researchers reported.

The results bolster the case for delaying school start times, as California recently did, according one researcher who was not involved in the study.
 

The ABCD Study

To examine how insufficient sleep affects children’s mental health, cognition, brain function, and brain structure over 2 years, Ze Wang, PhD, professor of diagnostic radiology and nuclear medicine at the University of Maryland, Baltimore, and colleagues analyzed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study is tracking the biologic and behavioral development of more than 11,000 children in the United States who were recruited for the study when they were 9 or 10 years old.

For their new analysis, Dr. Wang’s group focused on 6,042 participants: 3,021 children with insufficient sleep who were matched with an equal number of participants who were similar in many respects, including sex, socioeconomic status, and puberty status, except they got at least 9 hours of sleep. They also looked at outcomes 2 years later from 749 of the matched pairs who had results available.

The investigators determined sleep duration based on how parents answered the question: “How many hours of sleep does your child get on most nights in the past 6 months?” Possible answers included at least 9 hours, 8-9 hours, 7-8 hours, 5-7 hours, or less than 5 hours. They also looked at functional and structural MRI scans, test results, and responses to questionnaires.

Negative effects of inadequate sleep were spread over “several different domains including brain structure, function, cognition, behavior, and mental health,” Dr. Wang said.

The strength of the relationship between sleep duration and the various outcomes was “modest” and based on group averages, he said. So, a given child who does not sleep for 9 hours most nights won’t necessarily perform worse than a child who gets enough sleep.

Still, modest effects may accumulate and have lasting consequences, Dr. Wang said.
 

Crystallized intelligence

The researchers looked at 42 behavioral outcomes, 32 of which were significantly different between the groups. Four outcomes in particular – depression, thought problems, performance on a picture-vocabulary test, and crystallized intelligence – were areas where insufficient sleep seemed to have a larger negative effect.

Sleep duration’s relationship with crystallized intelligence was twice that for fluid intelligence, which does not depend on memory.

“Sleep affects memory,” Dr. Wang said. “Crystallized intelligence depends on learned skills and knowledge, which are memory. In this sense, sleep is related to crystallized intelligence.”

One limitation of the study is that some parents may not accurately report how much sleep their child gets, Dr. Wang acknowledged. Children may be awake when parents think they are asleep, for example.

And although the results show getting 9 hours of sleep may help neurocognitive development, it’s also possible that excessive amounts of sleep could be problematic, the study authors wrote.

Further experiments are needed to prove that insufficient sleep – and not some other, unaccounted for factor – causes the observed impairments in neurodevelopment.

To promote healthy sleep, parents should keep a strict routine for their children, such as a regular bedtime and no electronic devices in the bedroom, Dr. Wang suggested. More physical activity during the day also should help.

If children have high levels of stress and depression, “finding the source is critical,” he said. Likewise, clinicians should consider how mental health can affect their patients’ sleep.
 

More to healthy sleep than duration

“This study both aligns with and advances existing research on the importance of sufficient sleep for child well-being,” said Ariel A. Williamson, PhD, DBSM, a psychologist and pediatric sleep expert in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia and assistant professor of psychiatry and pediatrics at University of Pennsylvania, also in Philadelphia.

The researchers used rigorous propensity score matching, longitudinal data, and brain imaging, which are “innovative methods that provide more evidence on potential mechanisms linking insufficient sleep and child outcomes,” said Dr. Williamson, who was not involved in the study.

While the investigators focused on sleep duration, child sleep health is multidimensional and includes other elements like timing and perception of sleep quality, Dr. Williamson noted. “For example, some research shows that having a sleep schedule that varies night to night is linked to poor child outcomes.”

Dr. Williamson tells families and clinicians that “sleep is a pillar of health,” equal to diet and exercise. That said, sleep recommendations need to fit within a family’s life – taking into account after school activities and late-night homework sessions. But extending sleep by just “20-30 minutes can make a meaningful difference for daytime functioning,” Dr. Williamson said.
 

Start school later?

Researchers have only relatively recently begun to understand how insufficient sleep affects adolescent neurocognitive development long term, and this study provides “crucial evidence” about the consequences, Lydia Gabriela Speyer, PhD, said in an editorial published with the study. Dr. Speyer is affiliated with the department of psychology at the University of Cambridge (England).

“Given the novel finding that insufficient sleep is associated with changes in brain structure and connectivity that are long-lasting, early intervention is crucial because such neural changes are probably not reversible and might consequently affect adolescents’ development into adulthood,” Dr. Speyer wrote.

Delaying school start times could be one way to help kids get more sleep. The American Academy of Pediatrics and the American Academy of Sleep Medicine recommend that middle schools and high schools start no earlier than 8:30 a.m. to better align with students’ circadian rhythm, Dr. Speyer noted.

As it is in the United States, most schools start closer to 8 a.m. In California, though, a law that went into effect on July 1 prohibits high schools from starting before 8:30 a.m. Other states are weighing similar legislation.

The research was supported by the National Institutes of Health. Dr. Wang and his coauthors and Dr. Speyer had no conflict of interest disclosures. Dr. Williamson is a sleep expert for the Pediatric Sleep Council (www.babysleep.com), which provides free information about early childhood sleep, but she does not receive compensation for this role.
 

Children who do not get enough sleep for one night can be cranky, groggy, or meltdown prone the next day.

Over time, though, insufficient sleep may impair neurodevelopment in ways that can be measured on brain scans and tests long term, a new study shows.

Research published in The Lancet Child & Adolescent Health found that 9- and 10-year-olds who do not get at least 9 hours of sleep most nights tend to have less gray matter and smaller areas of the brain responsible for attention, memory, and inhibition control, relative to children who do get enough sleep.

The researchers also found a relationship between insufficient sleep and disrupted connections between the basal ganglia and cortical regions of the brain. These disruptions appeared to be linked to depression, thought problems, and impairments in crystallized intelligence, a type of intelligence that depends on memory.

The overall patterns persisted 2 years later, even as those who got enough sleep at baseline gradually slept less over time, while those who were not getting enough sleep to begin with continued to sleep about the same amount, the researchers reported.

The results bolster the case for delaying school start times, as California recently did, according one researcher who was not involved in the study.
 

The ABCD Study

To examine how insufficient sleep affects children’s mental health, cognition, brain function, and brain structure over 2 years, Ze Wang, PhD, professor of diagnostic radiology and nuclear medicine at the University of Maryland, Baltimore, and colleagues analyzed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study is tracking the biologic and behavioral development of more than 11,000 children in the United States who were recruited for the study when they were 9 or 10 years old.

For their new analysis, Dr. Wang’s group focused on 6,042 participants: 3,021 children with insufficient sleep who were matched with an equal number of participants who were similar in many respects, including sex, socioeconomic status, and puberty status, except they got at least 9 hours of sleep. They also looked at outcomes 2 years later from 749 of the matched pairs who had results available.

The investigators determined sleep duration based on how parents answered the question: “How many hours of sleep does your child get on most nights in the past 6 months?” Possible answers included at least 9 hours, 8-9 hours, 7-8 hours, 5-7 hours, or less than 5 hours. They also looked at functional and structural MRI scans, test results, and responses to questionnaires.

Negative effects of inadequate sleep were spread over “several different domains including brain structure, function, cognition, behavior, and mental health,” Dr. Wang said.

The strength of the relationship between sleep duration and the various outcomes was “modest” and based on group averages, he said. So, a given child who does not sleep for 9 hours most nights won’t necessarily perform worse than a child who gets enough sleep.

Still, modest effects may accumulate and have lasting consequences, Dr. Wang said.
 

Crystallized intelligence

The researchers looked at 42 behavioral outcomes, 32 of which were significantly different between the groups. Four outcomes in particular – depression, thought problems, performance on a picture-vocabulary test, and crystallized intelligence – were areas where insufficient sleep seemed to have a larger negative effect.

Sleep duration’s relationship with crystallized intelligence was twice that for fluid intelligence, which does not depend on memory.

“Sleep affects memory,” Dr. Wang said. “Crystallized intelligence depends on learned skills and knowledge, which are memory. In this sense, sleep is related to crystallized intelligence.”

One limitation of the study is that some parents may not accurately report how much sleep their child gets, Dr. Wang acknowledged. Children may be awake when parents think they are asleep, for example.

And although the results show getting 9 hours of sleep may help neurocognitive development, it’s also possible that excessive amounts of sleep could be problematic, the study authors wrote.

Further experiments are needed to prove that insufficient sleep – and not some other, unaccounted for factor – causes the observed impairments in neurodevelopment.

To promote healthy sleep, parents should keep a strict routine for their children, such as a regular bedtime and no electronic devices in the bedroom, Dr. Wang suggested. More physical activity during the day also should help.

If children have high levels of stress and depression, “finding the source is critical,” he said. Likewise, clinicians should consider how mental health can affect their patients’ sleep.
 

More to healthy sleep than duration

“This study both aligns with and advances existing research on the importance of sufficient sleep for child well-being,” said Ariel A. Williamson, PhD, DBSM, a psychologist and pediatric sleep expert in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia and assistant professor of psychiatry and pediatrics at University of Pennsylvania, also in Philadelphia.

The researchers used rigorous propensity score matching, longitudinal data, and brain imaging, which are “innovative methods that provide more evidence on potential mechanisms linking insufficient sleep and child outcomes,” said Dr. Williamson, who was not involved in the study.

While the investigators focused on sleep duration, child sleep health is multidimensional and includes other elements like timing and perception of sleep quality, Dr. Williamson noted. “For example, some research shows that having a sleep schedule that varies night to night is linked to poor child outcomes.”

Dr. Williamson tells families and clinicians that “sleep is a pillar of health,” equal to diet and exercise. That said, sleep recommendations need to fit within a family’s life – taking into account after school activities and late-night homework sessions. But extending sleep by just “20-30 minutes can make a meaningful difference for daytime functioning,” Dr. Williamson said.
 

Start school later?

Researchers have only relatively recently begun to understand how insufficient sleep affects adolescent neurocognitive development long term, and this study provides “crucial evidence” about the consequences, Lydia Gabriela Speyer, PhD, said in an editorial published with the study. Dr. Speyer is affiliated with the department of psychology at the University of Cambridge (England).

“Given the novel finding that insufficient sleep is associated with changes in brain structure and connectivity that are long-lasting, early intervention is crucial because such neural changes are probably not reversible and might consequently affect adolescents’ development into adulthood,” Dr. Speyer wrote.

Delaying school start times could be one way to help kids get more sleep. The American Academy of Pediatrics and the American Academy of Sleep Medicine recommend that middle schools and high schools start no earlier than 8:30 a.m. to better align with students’ circadian rhythm, Dr. Speyer noted.

As it is in the United States, most schools start closer to 8 a.m. In California, though, a law that went into effect on July 1 prohibits high schools from starting before 8:30 a.m. Other states are weighing similar legislation.

The research was supported by the National Institutes of Health. Dr. Wang and his coauthors and Dr. Speyer had no conflict of interest disclosures. Dr. Williamson is a sleep expert for the Pediatric Sleep Council (www.babysleep.com), which provides free information about early childhood sleep, but she does not receive compensation for this role.
 

Transcranial direct current stimulation (tDCS) using a home-based device can help improve attention in adults with attention-deficit/hyperactivity disorder who are not taking stimulants, new research suggests.

Results from the sham-controlled trial also showed that the tDCS treatment was both safe and well tolerated.

Overall, the findings suggest that the device could be a nondrug alternative for treating this patient population, Douglas Teixeira Leffa, MD, PhD, department of psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and colleagues note.

“This is particularly relevant since a vast body of literature describes low long-term adherence rates and persistence to pharmacological treatment in patients with ADHD,” they write.

The findings were published online in JAMA Psychiatry.
 

Avoiding office visits

A noninvasive technique that is easy to use and relatively inexpensive, tDCS involves applying a low-intensity current over the scalp to modulate cortical excitability and induce neuroplasticity. Home-use tDCS devices, which avoid the need for daily office visits for stimulation sessions, have been validated in previous clinical samples.

The current study included 64 adults with ADHD who are not taking stimulants. They had moderate or severe symptoms of inattention, with an inattention score of 21 or higher on the clinician-administered Adult ADHD Self-Report Scale version 1.1 (CASRS).

The CASRS includes nine questions related to inattention symptoms (CASRS-I) and nine related to hyperactivity-impulsivity symptoms (CASRS-HI). The score can vary from 0 to 36 for each domain, with higher scores indicating increased symptoms.

Researchers randomly assigned participants to receive either active or sham stimulation.

The tDCS device used in the study delivered a current with 35-cm² electrodes (7 cm by 5 cm). The anodal and cathodal electrodes were positioned corresponding to the right and left dorsolateral prefrontal cortex (DLPFC), respectively.

The investigators note that decreased activation in the right DLPFC has been reported before in patients with ADHD during tasks that require attention.

After learning to use the device, participants underwent 30-minute daily sessions of tDCS (2-mA direct constant current) for 4 weeks for a total of 28 sessions.

Devices programmed for sham treatment delivered a 30-second ramp-up (0-2 mA) stimulation followed by a 30-second ramp-down (2-0 mA) at the beginning, middle, and end of the application. This mimicked the tactile sensations reported with tDCS and has been shown to be a reliable sham protocol.

Participants were encouraged to perform the stimulation sessions at the same time of day. To improve adherence, they received daily text message reminders.

Nine patients discontinued treatment, two in the sham group and seven in the active group. However, patients who finished the trial completed a mean 25 of 28 sessions.
 

Window of opportunity?

The mean inattention score on CASRS-I at week 4, the primary outcome, was 18.88 in the active tDCS group vs. 23.63 in the sham tDCS group. There was a statistically significant treatment by time interaction for CASRS-I (beta interaction, –3.18; 95% confidence interval, –4.60 to –1.75; P < .001), showing decreased inattention symptoms in the active vs. sham groups.

The estimated Cohen’s d was 1.23 (95% CI, .67-1.78), indicating at least a moderate effect. This effect was similar to that reported with trigeminal nerve stimulation (TNS), the first approved device-based therapy for ADHD, and to that of atomoxetine, the second-line treatment for ADHD, the researchers note.

About one-third of patients (34.3%) in the active tDCS group achieved a 30% reduction in CASRS-I score, compared with 6.2% in the sham tDCS group.

There was no statistically significant difference in the secondary outcome of hyperactivity-impulsivity symptoms evaluated with the CASRS-HI. This may be because hyperactivity-impulsivity in ADHD is associated with a hypoactivation in the right inferior frontal cortex rather than the right DLPFC, the investigators write.

There were also no significant group differences in other secondary outcomes, including depression, anxiety, and executive function.

Adverse events (AE) were mostly mild and included skin redness and scalp burn. There were no severe or serious AEs.

Using a home-based tDCS device allows for considerably more sessions, with 28 being the highest number so far applied to patients with ADHD. This, the researchers note, is important because evidence suggests increased efficacy of tDCS with extended periods of treatment.

The home-based device “opens a new window of opportunity, especially for participants who live in geographically remote areas or have physical or cognitive disabilities that may hinder access to clinical centers,” they write.

Although a study limitation was the relatively high dropout rate in the active group, which might bias interpretation of the findings, only two of seven dropouts in the active group left because of an AE, the investigators note.

Patients received training in using the device, but there was no remote monitoring of sessions. In addition, the study population, which was relatively homogeneous with participants having no moderate to severe symptoms of depression or anxiety, differed from the usual patients with ADHD who are treated in clinical centers, the researchers point out.

As well, the study included only patients not taking pharmacologic treatment for ADHD – so the findings might not be generalizable to other patients, they add.
 

‘Just a first step’

Commenting on the study, Mark George, MD, distinguished professor of psychiatry, radiology, and neurology, Medical University of South Carolina, Charleston, noted that although this was a single-center study with a relatively small sample size, it is still important.

Showing it is possible to do high-quality tDCS studies at home “is a huge advance,” said Dr. George, who was not involved with the research.

“Home treatment is cheaper and easier for patients and allows many people to get treatment who would not be able to make it to the clinic daily for treatment,” he added.

He noted the study showed “a clear improvement in ADHD,” which is important because better treatments are needed.

However, he cautioned that this is “just a first step” and more studies are needed. For example, he said, it is not clear whether improvements persist and if patients need to self-treat forever, as they would with a medication.

Dr. George also noted that although the study used “a pioneering research device” with several safety features, many home-based tDCS devices on the market do not have those.

“I don’t advise patients to do this now. Further studies are needed for FDA approval and general public use,” he said.

The study was funded by the National Council for Scientific and Technological Development, the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, the Brain & Behavior Research Foundation, Fundação de Amparo à Pesquisa do Estado de São Paulo, and the Brazilian Innovation Agency. Dr. Leffa reported having received grants from the Brain & Behavior Research Foundation, the National Council for Scientific and Technological Development, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul during the conduction of the study. Dr. George reported no relevant financial relationships.

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

Transcranial direct current stimulation (tDCS) using a home-based device can help improve attention in adults with attention-deficit/hyperactivity disorder who are not taking stimulants, new research suggests.

Results from the sham-controlled trial also showed that the tDCS treatment was both safe and well tolerated.

Overall, the findings suggest that the device could be a nondrug alternative for treating this patient population, Douglas Teixeira Leffa, MD, PhD, department of psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and colleagues note.

“This is particularly relevant since a vast body of literature describes low long-term adherence rates and persistence to pharmacological treatment in patients with ADHD,” they write.

The findings were published online in JAMA Psychiatry.
 

Avoiding office visits

A noninvasive technique that is easy to use and relatively inexpensive, tDCS involves applying a low-intensity current over the scalp to modulate cortical excitability and induce neuroplasticity. Home-use tDCS devices, which avoid the need for daily office visits for stimulation sessions, have been validated in previous clinical samples.

The current study included 64 adults with ADHD who are not taking stimulants. They had moderate or severe symptoms of inattention, with an inattention score of 21 or higher on the clinician-administered Adult ADHD Self-Report Scale version 1.1 (CASRS).

The CASRS includes nine questions related to inattention symptoms (CASRS-I) and nine related to hyperactivity-impulsivity symptoms (CASRS-HI). The score can vary from 0 to 36 for each domain, with higher scores indicating increased symptoms.

Researchers randomly assigned participants to receive either active or sham stimulation.

The tDCS device used in the study delivered a current with 35-cm² electrodes (7 cm by 5 cm). The anodal and cathodal electrodes were positioned corresponding to the right and left dorsolateral prefrontal cortex (DLPFC), respectively.

The investigators note that decreased activation in the right DLPFC has been reported before in patients with ADHD during tasks that require attention.

After learning to use the device, participants underwent 30-minute daily sessions of tDCS (2-mA direct constant current) for 4 weeks for a total of 28 sessions.

Devices programmed for sham treatment delivered a 30-second ramp-up (0-2 mA) stimulation followed by a 30-second ramp-down (2-0 mA) at the beginning, middle, and end of the application. This mimicked the tactile sensations reported with tDCS and has been shown to be a reliable sham protocol.

Participants were encouraged to perform the stimulation sessions at the same time of day. To improve adherence, they received daily text message reminders.

Nine patients discontinued treatment, two in the sham group and seven in the active group. However, patients who finished the trial completed a mean 25 of 28 sessions.
 

Window of opportunity?

The mean inattention score on CASRS-I at week 4, the primary outcome, was 18.88 in the active tDCS group vs. 23.63 in the sham tDCS group. There was a statistically significant treatment by time interaction for CASRS-I (beta interaction, –3.18; 95% confidence interval, –4.60 to –1.75; P < .001), showing decreased inattention symptoms in the active vs. sham groups.

The estimated Cohen’s d was 1.23 (95% CI, .67-1.78), indicating at least a moderate effect. This effect was similar to that reported with trigeminal nerve stimulation (TNS), the first approved device-based therapy for ADHD, and to that of atomoxetine, the second-line treatment for ADHD, the researchers note.

About one-third of patients (34.3%) in the active tDCS group achieved a 30% reduction in CASRS-I score, compared with 6.2% in the sham tDCS group.

There was no statistically significant difference in the secondary outcome of hyperactivity-impulsivity symptoms evaluated with the CASRS-HI. This may be because hyperactivity-impulsivity in ADHD is associated with a hypoactivation in the right inferior frontal cortex rather than the right DLPFC, the investigators write.

There were also no significant group differences in other secondary outcomes, including depression, anxiety, and executive function.

Adverse events (AE) were mostly mild and included skin redness and scalp burn. There were no severe or serious AEs.

Using a home-based tDCS device allows for considerably more sessions, with 28 being the highest number so far applied to patients with ADHD. This, the researchers note, is important because evidence suggests increased efficacy of tDCS with extended periods of treatment.

The home-based device “opens a new window of opportunity, especially for participants who live in geographically remote areas or have physical or cognitive disabilities that may hinder access to clinical centers,” they write.

Although a study limitation was the relatively high dropout rate in the active group, which might bias interpretation of the findings, only two of seven dropouts in the active group left because of an AE, the investigators note.

Patients received training in using the device, but there was no remote monitoring of sessions. In addition, the study population, which was relatively homogeneous with participants having no moderate to severe symptoms of depression or anxiety, differed from the usual patients with ADHD who are treated in clinical centers, the researchers point out.

As well, the study included only patients not taking pharmacologic treatment for ADHD – so the findings might not be generalizable to other patients, they add.
 

‘Just a first step’

Commenting on the study, Mark George, MD, distinguished professor of psychiatry, radiology, and neurology, Medical University of South Carolina, Charleston, noted that although this was a single-center study with a relatively small sample size, it is still important.

Showing it is possible to do high-quality tDCS studies at home “is a huge advance,” said Dr. George, who was not involved with the research.

“Home treatment is cheaper and easier for patients and allows many people to get treatment who would not be able to make it to the clinic daily for treatment,” he added.

He noted the study showed “a clear improvement in ADHD,” which is important because better treatments are needed.

However, he cautioned that this is “just a first step” and more studies are needed. For example, he said, it is not clear whether improvements persist and if patients need to self-treat forever, as they would with a medication.

Dr. George also noted that although the study used “a pioneering research device” with several safety features, many home-based tDCS devices on the market do not have those.

“I don’t advise patients to do this now. Further studies are needed for FDA approval and general public use,” he said.

The study was funded by the National Council for Scientific and Technological Development, the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, the Brain & Behavior Research Foundation, Fundação de Amparo à Pesquisa do Estado de São Paulo, and the Brazilian Innovation Agency. Dr. Leffa reported having received grants from the Brain & Behavior Research Foundation, the National Council for Scientific and Technological Development, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul during the conduction of the study. Dr. George reported no relevant financial relationships.

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

Transcranial direct current stimulation (tDCS) using a home-based device can help improve attention in adults with attention-deficit/hyperactivity disorder who are not taking stimulants, new research suggests.

Results from the sham-controlled trial also showed that the tDCS treatment was both safe and well tolerated.

Overall, the findings suggest that the device could be a nondrug alternative for treating this patient population, Douglas Teixeira Leffa, MD, PhD, department of psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and colleagues note.

“This is particularly relevant since a vast body of literature describes low long-term adherence rates and persistence to pharmacological treatment in patients with ADHD,” they write.

The findings were published online in JAMA Psychiatry.
 

Avoiding office visits

A noninvasive technique that is easy to use and relatively inexpensive, tDCS involves applying a low-intensity current over the scalp to modulate cortical excitability and induce neuroplasticity. Home-use tDCS devices, which avoid the need for daily office visits for stimulation sessions, have been validated in previous clinical samples.

The current study included 64 adults with ADHD who are not taking stimulants. They had moderate or severe symptoms of inattention, with an inattention score of 21 or higher on the clinician-administered Adult ADHD Self-Report Scale version 1.1 (CASRS).

The CASRS includes nine questions related to inattention symptoms (CASRS-I) and nine related to hyperactivity-impulsivity symptoms (CASRS-HI). The score can vary from 0 to 36 for each domain, with higher scores indicating increased symptoms.

Researchers randomly assigned participants to receive either active or sham stimulation.

The tDCS device used in the study delivered a current with 35-cm² electrodes (7 cm by 5 cm). The anodal and cathodal electrodes were positioned corresponding to the right and left dorsolateral prefrontal cortex (DLPFC), respectively.

The investigators note that decreased activation in the right DLPFC has been reported before in patients with ADHD during tasks that require attention.

After learning to use the device, participants underwent 30-minute daily sessions of tDCS (2-mA direct constant current) for 4 weeks for a total of 28 sessions.

Devices programmed for sham treatment delivered a 30-second ramp-up (0-2 mA) stimulation followed by a 30-second ramp-down (2-0 mA) at the beginning, middle, and end of the application. This mimicked the tactile sensations reported with tDCS and has been shown to be a reliable sham protocol.

Participants were encouraged to perform the stimulation sessions at the same time of day. To improve adherence, they received daily text message reminders.

Nine patients discontinued treatment, two in the sham group and seven in the active group. However, patients who finished the trial completed a mean 25 of 28 sessions.
 

Window of opportunity?

The mean inattention score on CASRS-I at week 4, the primary outcome, was 18.88 in the active tDCS group vs. 23.63 in the sham tDCS group. There was a statistically significant treatment by time interaction for CASRS-I (beta interaction, –3.18; 95% confidence interval, –4.60 to –1.75; P < .001), showing decreased inattention symptoms in the active vs. sham groups.

The estimated Cohen’s d was 1.23 (95% CI, .67-1.78), indicating at least a moderate effect. This effect was similar to that reported with trigeminal nerve stimulation (TNS), the first approved device-based therapy for ADHD, and to that of atomoxetine, the second-line treatment for ADHD, the researchers note.

About one-third of patients (34.3%) in the active tDCS group achieved a 30% reduction in CASRS-I score, compared with 6.2% in the sham tDCS group.

There was no statistically significant difference in the secondary outcome of hyperactivity-impulsivity symptoms evaluated with the CASRS-HI. This may be because hyperactivity-impulsivity in ADHD is associated with a hypoactivation in the right inferior frontal cortex rather than the right DLPFC, the investigators write.

There were also no significant group differences in other secondary outcomes, including depression, anxiety, and executive function.

Adverse events (AE) were mostly mild and included skin redness and scalp burn. There were no severe or serious AEs.

Using a home-based tDCS device allows for considerably more sessions, with 28 being the highest number so far applied to patients with ADHD. This, the researchers note, is important because evidence suggests increased efficacy of tDCS with extended periods of treatment.

The home-based device “opens a new window of opportunity, especially for participants who live in geographically remote areas or have physical or cognitive disabilities that may hinder access to clinical centers,” they write.

Although a study limitation was the relatively high dropout rate in the active group, which might bias interpretation of the findings, only two of seven dropouts in the active group left because of an AE, the investigators note.

Patients received training in using the device, but there was no remote monitoring of sessions. In addition, the study population, which was relatively homogeneous with participants having no moderate to severe symptoms of depression or anxiety, differed from the usual patients with ADHD who are treated in clinical centers, the researchers point out.

As well, the study included only patients not taking pharmacologic treatment for ADHD – so the findings might not be generalizable to other patients, they add.
 

‘Just a first step’

Commenting on the study, Mark George, MD, distinguished professor of psychiatry, radiology, and neurology, Medical University of South Carolina, Charleston, noted that although this was a single-center study with a relatively small sample size, it is still important.

Showing it is possible to do high-quality tDCS studies at home “is a huge advance,” said Dr. George, who was not involved with the research.

“Home treatment is cheaper and easier for patients and allows many people to get treatment who would not be able to make it to the clinic daily for treatment,” he added.

He noted the study showed “a clear improvement in ADHD,” which is important because better treatments are needed.

However, he cautioned that this is “just a first step” and more studies are needed. For example, he said, it is not clear whether improvements persist and if patients need to self-treat forever, as they would with a medication.

Dr. George also noted that although the study used “a pioneering research device” with several safety features, many home-based tDCS devices on the market do not have those.

“I don’t advise patients to do this now. Further studies are needed for FDA approval and general public use,” he said.

The study was funded by the National Council for Scientific and Technological Development, the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, the Brain & Behavior Research Foundation, Fundação de Amparo à Pesquisa do Estado de São Paulo, and the Brazilian Innovation Agency. Dr. Leffa reported having received grants from the Brain & Behavior Research Foundation, the National Council for Scientific and Technological Development, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul during the conduction of the study. Dr. George reported no relevant financial relationships.

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

Halfway through her first round of chemotherapy, with hair falling out, weight down, and her brain in a fog, Carolyn Hackett sat down for a Zoom meeting with a team of oncologists.

She didn’t even want a second opinion, but a friend had insisted that she get one, and she had agreed for the sake of their friendship.

But that Zoom meeting likely saved her life. The team of five specialists who had been reviewing her case for a week explained that she had been misdiagnosed. The original pathologist was mistaken. She didn’t have Hodgkin lymphoma; her cancer was really non-Hodgkin T-cell lymphoma. And the chemotherapy regimen she was in the middle of would do nothing to stop it.

The panel of doctors who populated Hackett’s computer screen during that December 2020 Zoom call were all volunteers with an organization called thesecondopinion, based in San Francisco.

The group, organized in 1969, currently offers free second opinions to at least three California patients with cancer each week. Patients meet for an average of 30-40 minutes – though there is really no limit – with a panel of doctors who have expertise in their specific case.

More than 70 cancer-related specialists, both current and retired, make up the roster of volunteers. A paid staffer rounds up a patient’s medical records, imaging and pathology slides. And a team of four to five doctors spends a week reviewing each case.

Then they meet directly with the patient and their doctor to answer questions and deliver their consensus.

Ms. Hackett was in disbelief after her meeting with thesecondopinion. Her diagnosis had gone from bad to worse, but the new information had changed her life. Without it, she would have surely continued chemotherapy and died.

On top of the new acccurate diagnosis, Ms. Hackett said it was a relief and reassurance when the team of volunteer doctors honored and included her oncologist. “I’m a nurse,” she said, and so she knows through experience that medicine comes with egos and frequent risk of lawsuits. But the team from thesecondopinion never criticized her doctor – after all, it wasn’t his mistake anyway – nor did they suggest legal action. Instead, they immediately included him as part of the team and sent him a letter detailing the panel concensus, she said, which made her feel safe.
 

Second opinions are big business

Medical second opinions are a large and growing industry projected to be worth more than $9.7 billion by 2027. There are already many services across the United States and worldwide devoted to providing second opinions specifically for patients with cancer.

“And rightly so,” says Alan Venook, MD, a professor of medicine at UCSF with experience and expertise in gastrointestinal malignancies who was approached for comment but is not associated with thesecondopinion. Cancer is an increasingly a sub-specialized area, and every patient should get a second opinion, he said in an interview.

What is unique to an appointment with thesecondopinion, however, is the price tag – $0.

By comparison, a virtual second opinion at the Cleveland Clinic comes at a flat rate of $1,850, and at the Dana-Farber Cancer Institute, Boston, the cost is $2,400.

At UCSF, a second opinion from Dr. Venook and his colleagues will cost patients a couple thousand dollars out-of-pocket, he said. “Many patients don’t have the luxury of paying for a second opinion,” he said.
 

More than looking for misdiagnosis

Research shows that getting a second opinion can significantly change the course of a patient’s disease and treatment. A 2017 study by the Mayo Clinic found that at their institution, around 22% of second opinions changed the diagnosis, and 66% of patients received a refined or redefined diagnosis.

However, a misdiagnosis – such the case presented by Ms. Hackett – is a rare occurrence at thesecondopinion, said Howard Kleckner, MD, a medical oncologist and the organization’s medical director.

“We aren’t in the business to look for mistakes,” he said.

More often, thesecondopinion panels are about clarifying and helping patients understand the disease and options they have.”People with cancer need to make a peace with it and make peace with the treatment,” Dr. Kleckner said.

He estimates that 90% of the patients that come to the group already have the right diagnosis and treatment plan because, he says, there are “very good doctors in the state and in the Bay Area in particular.”

And even in the case of the remaining 10% of patients whose second opinion differs from their first, it’s largely a case of differences in the staging the disease or treatment options, Dr. Kleckner said.

“We aren’t coming up with brilliant suggestions. Often we are agreeing with what’s already been said,” said David Lakes, MD, a retired medical oncologist who has been volunteering with thesecondopinion for more than 30 years. “But we often see people understand for the first time.”

Both Dr. Kleckner and Dr. Lakes say that the organization attracts a certain kind of doctor, who tends to be an excellent communicator and really cares about helping the patients.

Many of these doctors are retired, but they want to keep doing the work, and they understand which pieces of information are most important for patients to know, Dr. Kleckner told this news organization. They are also willing to do this kind of work even when they won’t get paid, Dr. Kleckner said.

Part of that comes with gray hair and storied careers, Dr. Lakes added. “Retired people have experience and judgment and communication skills that a lot of younger doctors don’t have,” he commented. They often have more experience with some of the tough stuff, like exploring the goals of treatment, discontinuing treatment, and end-of-life care, and they also have more time to engage patients on their emotional health, he said.

Dr. Venook said that the services provided free-of-charge by these volunteers is “laudable,” and their thorough review of all the diagnostic information is “to their credit.” But he questions whether every second opinion provided by the organization is an expert one, since the doctors are no longer practicing. Oncology is a particularly fast-moving field, with many new developments and novel drugs launched in recent years.

“Second opinions are incredibly helpful but [have] to be [provided] by a knowledgeable expert who gets all the details and gives it serious thought,” Dr. Venook said.

Dr. Lakes says that he is constantly evaluating whether he is entitled to keep offering second opinions when he isn’t practicing; so far the answer remains a yes. Although he now has to spend more time researching treatment options like biologics, he still feels adept at engaging with patients and helping patients understand where they are in their illness and the potential benefits of fourth- or fifth-line treatments.

Another strength of thesecondopinion model lies in numbers. Most of the time second opinions are given by one doctor, Dr. Kleckner pointed out. In contrast, thesecondopinion provides the patient with access to a whole team of specialists.

“Sometimes people on the panels don’t completely agree,” Dr. Lakes said. So, before meeting with the patient on Zoom, the doctors review the case together for about half an hour and come up with a consensus. This way there’s no mixed messaging and as little anxiety for the patient as possible, he said.

The fact that patients have direct access to the panel of experts who review their cases is unique in itself, Dr. Kleckner said.

Many hospitals have tumor boards, but they are reserved for physicians, he pointed out. Patients get to hear the board’s opinion secondhand through their primary doctor or oncologist.

But at thesecondopinion, the patient gets to engage with the doctors directly. There is time to review up to four questions that the patient has submitted before the meeting and also time for any additional questions that may have arisen during the course of the meeting.

In oncology, and medicine in general, patients are often shuffled from one specialist to another, Dr. Lakes said. But often, there is no one who takes a steps back to see the whole picture.

That’s part of what thesecondopinion offers, he said. “We have the time, the experience, and no skin in the game. We can think about [the cases] in an intellectual way without feeling like we are in the hot seat or in charge.”

Thanks to her second opinion, Ms. Hackett was able to get connected with an oncologist in San Francisco who specializes in the type of cancer she actually had. She went on to receive nine rounds of a monoclonal antibody treatment formulated for her specific cancer. She is now in remission 6 months after finishing that therapy.

Scans in late July showed that she was cancer-free and doing really well. “I’m so grateful to them. I’m so impressed with thesecondopinion, I can’t believe it,” she said. “I’m alive because of them.”

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

Halfway through her first round of chemotherapy, with hair falling out, weight down, and her brain in a fog, Carolyn Hackett sat down for a Zoom meeting with a team of oncologists.

She didn’t even want a second opinion, but a friend had insisted that she get one, and she had agreed for the sake of their friendship.

But that Zoom meeting likely saved her life. The team of five specialists who had been reviewing her case for a week explained that she had been misdiagnosed. The original pathologist was mistaken. She didn’t have Hodgkin lymphoma; her cancer was really non-Hodgkin T-cell lymphoma. And the chemotherapy regimen she was in the middle of would do nothing to stop it.

The panel of doctors who populated Hackett’s computer screen during that December 2020 Zoom call were all volunteers with an organization called thesecondopinion, based in San Francisco.

The group, organized in 1969, currently offers free second opinions to at least three California patients with cancer each week. Patients meet for an average of 30-40 minutes – though there is really no limit – with a panel of doctors who have expertise in their specific case.

More than 70 cancer-related specialists, both current and retired, make up the roster of volunteers. A paid staffer rounds up a patient’s medical records, imaging and pathology slides. And a team of four to five doctors spends a week reviewing each case.

Then they meet directly with the patient and their doctor to answer questions and deliver their consensus.

Ms. Hackett was in disbelief after her meeting with thesecondopinion. Her diagnosis had gone from bad to worse, but the new information had changed her life. Without it, she would have surely continued chemotherapy and died.

On top of the new acccurate diagnosis, Ms. Hackett said it was a relief and reassurance when the team of volunteer doctors honored and included her oncologist. “I’m a nurse,” she said, and so she knows through experience that medicine comes with egos and frequent risk of lawsuits. But the team from thesecondopinion never criticized her doctor – after all, it wasn’t his mistake anyway – nor did they suggest legal action. Instead, they immediately included him as part of the team and sent him a letter detailing the panel concensus, she said, which made her feel safe.
 

Second opinions are big business

Medical second opinions are a large and growing industry projected to be worth more than $9.7 billion by 2027. There are already many services across the United States and worldwide devoted to providing second opinions specifically for patients with cancer.

“And rightly so,” says Alan Venook, MD, a professor of medicine at UCSF with experience and expertise in gastrointestinal malignancies who was approached for comment but is not associated with thesecondopinion. Cancer is an increasingly a sub-specialized area, and every patient should get a second opinion, he said in an interview.

What is unique to an appointment with thesecondopinion, however, is the price tag – $0.

By comparison, a virtual second opinion at the Cleveland Clinic comes at a flat rate of $1,850, and at the Dana-Farber Cancer Institute, Boston, the cost is $2,400.

At UCSF, a second opinion from Dr. Venook and his colleagues will cost patients a couple thousand dollars out-of-pocket, he said. “Many patients don’t have the luxury of paying for a second opinion,” he said.
 

More than looking for misdiagnosis

Research shows that getting a second opinion can significantly change the course of a patient’s disease and treatment. A 2017 study by the Mayo Clinic found that at their institution, around 22% of second opinions changed the diagnosis, and 66% of patients received a refined or redefined diagnosis.

However, a misdiagnosis – such the case presented by Ms. Hackett – is a rare occurrence at thesecondopinion, said Howard Kleckner, MD, a medical oncologist and the organization’s medical director.

“We aren’t in the business to look for mistakes,” he said.

More often, thesecondopinion panels are about clarifying and helping patients understand the disease and options they have.”People with cancer need to make a peace with it and make peace with the treatment,” Dr. Kleckner said.

He estimates that 90% of the patients that come to the group already have the right diagnosis and treatment plan because, he says, there are “very good doctors in the state and in the Bay Area in particular.”

And even in the case of the remaining 10% of patients whose second opinion differs from their first, it’s largely a case of differences in the staging the disease or treatment options, Dr. Kleckner said.

“We aren’t coming up with brilliant suggestions. Often we are agreeing with what’s already been said,” said David Lakes, MD, a retired medical oncologist who has been volunteering with thesecondopinion for more than 30 years. “But we often see people understand for the first time.”

Both Dr. Kleckner and Dr. Lakes say that the organization attracts a certain kind of doctor, who tends to be an excellent communicator and really cares about helping the patients.

Many of these doctors are retired, but they want to keep doing the work, and they understand which pieces of information are most important for patients to know, Dr. Kleckner told this news organization. They are also willing to do this kind of work even when they won’t get paid, Dr. Kleckner said.

Part of that comes with gray hair and storied careers, Dr. Lakes added. “Retired people have experience and judgment and communication skills that a lot of younger doctors don’t have,” he commented. They often have more experience with some of the tough stuff, like exploring the goals of treatment, discontinuing treatment, and end-of-life care, and they also have more time to engage patients on their emotional health, he said.

Dr. Venook said that the services provided free-of-charge by these volunteers is “laudable,” and their thorough review of all the diagnostic information is “to their credit.” But he questions whether every second opinion provided by the organization is an expert one, since the doctors are no longer practicing. Oncology is a particularly fast-moving field, with many new developments and novel drugs launched in recent years.

“Second opinions are incredibly helpful but [have] to be [provided] by a knowledgeable expert who gets all the details and gives it serious thought,” Dr. Venook said.

Dr. Lakes says that he is constantly evaluating whether he is entitled to keep offering second opinions when he isn’t practicing; so far the answer remains a yes. Although he now has to spend more time researching treatment options like biologics, he still feels adept at engaging with patients and helping patients understand where they are in their illness and the potential benefits of fourth- or fifth-line treatments.

Another strength of thesecondopinion model lies in numbers. Most of the time second opinions are given by one doctor, Dr. Kleckner pointed out. In contrast, thesecondopinion provides the patient with access to a whole team of specialists.

“Sometimes people on the panels don’t completely agree,” Dr. Lakes said. So, before meeting with the patient on Zoom, the doctors review the case together for about half an hour and come up with a consensus. This way there’s no mixed messaging and as little anxiety for the patient as possible, he said.

The fact that patients have direct access to the panel of experts who review their cases is unique in itself, Dr. Kleckner said.

Many hospitals have tumor boards, but they are reserved for physicians, he pointed out. Patients get to hear the board’s opinion secondhand through their primary doctor or oncologist.

But at thesecondopinion, the patient gets to engage with the doctors directly. There is time to review up to four questions that the patient has submitted before the meeting and also time for any additional questions that may have arisen during the course of the meeting.

In oncology, and medicine in general, patients are often shuffled from one specialist to another, Dr. Lakes said. But often, there is no one who takes a steps back to see the whole picture.

That’s part of what thesecondopinion offers, he said. “We have the time, the experience, and no skin in the game. We can think about [the cases] in an intellectual way without feeling like we are in the hot seat or in charge.”

Thanks to her second opinion, Ms. Hackett was able to get connected with an oncologist in San Francisco who specializes in the type of cancer she actually had. She went on to receive nine rounds of a monoclonal antibody treatment formulated for her specific cancer. She is now in remission 6 months after finishing that therapy.

Scans in late July showed that she was cancer-free and doing really well. “I’m so grateful to them. I’m so impressed with thesecondopinion, I can’t believe it,” she said. “I’m alive because of them.”

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

Halfway through her first round of chemotherapy, with hair falling out, weight down, and her brain in a fog, Carolyn Hackett sat down for a Zoom meeting with a team of oncologists.

She didn’t even want a second opinion, but a friend had insisted that she get one, and she had agreed for the sake of their friendship.

But that Zoom meeting likely saved her life. The team of five specialists who had been reviewing her case for a week explained that she had been misdiagnosed. The original pathologist was mistaken. She didn’t have Hodgkin lymphoma; her cancer was really non-Hodgkin T-cell lymphoma. And the chemotherapy regimen she was in the middle of would do nothing to stop it.

The panel of doctors who populated Hackett’s computer screen during that December 2020 Zoom call were all volunteers with an organization called thesecondopinion, based in San Francisco.

The group, organized in 1969, currently offers free second opinions to at least three California patients with cancer each week. Patients meet for an average of 30-40 minutes – though there is really no limit – with a panel of doctors who have expertise in their specific case.

More than 70 cancer-related specialists, both current and retired, make up the roster of volunteers. A paid staffer rounds up a patient’s medical records, imaging and pathology slides. And a team of four to five doctors spends a week reviewing each case.

Then they meet directly with the patient and their doctor to answer questions and deliver their consensus.

Ms. Hackett was in disbelief after her meeting with thesecondopinion. Her diagnosis had gone from bad to worse, but the new information had changed her life. Without it, she would have surely continued chemotherapy and died.

On top of the new acccurate diagnosis, Ms. Hackett said it was a relief and reassurance when the team of volunteer doctors honored and included her oncologist. “I’m a nurse,” she said, and so she knows through experience that medicine comes with egos and frequent risk of lawsuits. But the team from thesecondopinion never criticized her doctor – after all, it wasn’t his mistake anyway – nor did they suggest legal action. Instead, they immediately included him as part of the team and sent him a letter detailing the panel concensus, she said, which made her feel safe.
 

Second opinions are big business

Medical second opinions are a large and growing industry projected to be worth more than $9.7 billion by 2027. There are already many services across the United States and worldwide devoted to providing second opinions specifically for patients with cancer.

“And rightly so,” says Alan Venook, MD, a professor of medicine at UCSF with experience and expertise in gastrointestinal malignancies who was approached for comment but is not associated with thesecondopinion. Cancer is an increasingly a sub-specialized area, and every patient should get a second opinion, he said in an interview.

What is unique to an appointment with thesecondopinion, however, is the price tag – $0.

By comparison, a virtual second opinion at the Cleveland Clinic comes at a flat rate of $1,850, and at the Dana-Farber Cancer Institute, Boston, the cost is $2,400.

At UCSF, a second opinion from Dr. Venook and his colleagues will cost patients a couple thousand dollars out-of-pocket, he said. “Many patients don’t have the luxury of paying for a second opinion,” he said.
 

More than looking for misdiagnosis

Research shows that getting a second opinion can significantly change the course of a patient’s disease and treatment. A 2017 study by the Mayo Clinic found that at their institution, around 22% of second opinions changed the diagnosis, and 66% of patients received a refined or redefined diagnosis.

However, a misdiagnosis – such the case presented by Ms. Hackett – is a rare occurrence at thesecondopinion, said Howard Kleckner, MD, a medical oncologist and the organization’s medical director.

“We aren’t in the business to look for mistakes,” he said.

More often, thesecondopinion panels are about clarifying and helping patients understand the disease and options they have.”People with cancer need to make a peace with it and make peace with the treatment,” Dr. Kleckner said.

He estimates that 90% of the patients that come to the group already have the right diagnosis and treatment plan because, he says, there are “very good doctors in the state and in the Bay Area in particular.”

And even in the case of the remaining 10% of patients whose second opinion differs from their first, it’s largely a case of differences in the staging the disease or treatment options, Dr. Kleckner said.

“We aren’t coming up with brilliant suggestions. Often we are agreeing with what’s already been said,” said David Lakes, MD, a retired medical oncologist who has been volunteering with thesecondopinion for more than 30 years. “But we often see people understand for the first time.”

Both Dr. Kleckner and Dr. Lakes say that the organization attracts a certain kind of doctor, who tends to be an excellent communicator and really cares about helping the patients.

Many of these doctors are retired, but they want to keep doing the work, and they understand which pieces of information are most important for patients to know, Dr. Kleckner told this news organization. They are also willing to do this kind of work even when they won’t get paid, Dr. Kleckner said.

Part of that comes with gray hair and storied careers, Dr. Lakes added. “Retired people have experience and judgment and communication skills that a lot of younger doctors don’t have,” he commented. They often have more experience with some of the tough stuff, like exploring the goals of treatment, discontinuing treatment, and end-of-life care, and they also have more time to engage patients on their emotional health, he said.

Dr. Venook said that the services provided free-of-charge by these volunteers is “laudable,” and their thorough review of all the diagnostic information is “to their credit.” But he questions whether every second opinion provided by the organization is an expert one, since the doctors are no longer practicing. Oncology is a particularly fast-moving field, with many new developments and novel drugs launched in recent years.

“Second opinions are incredibly helpful but [have] to be [provided] by a knowledgeable expert who gets all the details and gives it serious thought,” Dr. Venook said.

Dr. Lakes says that he is constantly evaluating whether he is entitled to keep offering second opinions when he isn’t practicing; so far the answer remains a yes. Although he now has to spend more time researching treatment options like biologics, he still feels adept at engaging with patients and helping patients understand where they are in their illness and the potential benefits of fourth- or fifth-line treatments.

Another strength of thesecondopinion model lies in numbers. Most of the time second opinions are given by one doctor, Dr. Kleckner pointed out. In contrast, thesecondopinion provides the patient with access to a whole team of specialists.

“Sometimes people on the panels don’t completely agree,” Dr. Lakes said. So, before meeting with the patient on Zoom, the doctors review the case together for about half an hour and come up with a consensus. This way there’s no mixed messaging and as little anxiety for the patient as possible, he said.

The fact that patients have direct access to the panel of experts who review their cases is unique in itself, Dr. Kleckner said.

Many hospitals have tumor boards, but they are reserved for physicians, he pointed out. Patients get to hear the board’s opinion secondhand through their primary doctor or oncologist.

But at thesecondopinion, the patient gets to engage with the doctors directly. There is time to review up to four questions that the patient has submitted before the meeting and also time for any additional questions that may have arisen during the course of the meeting.

In oncology, and medicine in general, patients are often shuffled from one specialist to another, Dr. Lakes said. But often, there is no one who takes a steps back to see the whole picture.

That’s part of what thesecondopinion offers, he said. “We have the time, the experience, and no skin in the game. We can think about [the cases] in an intellectual way without feeling like we are in the hot seat or in charge.”

Thanks to her second opinion, Ms. Hackett was able to get connected with an oncologist in San Francisco who specializes in the type of cancer she actually had. She went on to receive nine rounds of a monoclonal antibody treatment formulated for her specific cancer. She is now in remission 6 months after finishing that therapy.

Scans in late July showed that she was cancer-free and doing really well. “I’m so grateful to them. I’m so impressed with thesecondopinion, I can’t believe it,” she said. “I’m alive because of them.”

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

PARIS – France is boosting its vaccination campaign in response to the increase in cases of monkeypox. After a sluggish start, newly appointed French health minister François Braun has announced the release of 42,000 vaccine doses. At the same time, medical students will be able to lend a helping hand at vaccination sites. However, some experts have criticized the measures taken as being too lax to combat what the World Health Organization has designated a global health emergency.

For Benjamin Davido, MD, MSc, PhD, an infectious disease specialist at the Raymond-Poincaré Hospital (Paris Public Hospital Trust, AP-HP, Garches region), the risks of this disease have been minimized and the measures taken are not adequate, despite the ready availability of the tools needed to manage the epidemic. We must remain alert to the risks posed by this monkeypox epidemic, which seems different from the sporadic outbreaks that usually crop up in Central and West Africa, he said. Dr. Davido recently shared his opinions in an interview.

Question: What do you think about the monkeypox vaccination campaign currently underway in France?

Dr. Davido: It doesn’t go far enough, and I am surprised by the lack of a concrete and specific objective. The effects of the disease are being minimized, and we seem to be in limbo. It seems we have to wait until the fire is out of control before we can call the fire department. We should have been more reactive and taken a more drastic approach from the get-go. In France, as in other countries affected by this epidemic, we are still, unfortunately, in a phase of observation, reassuring ourselves that this will surely not become another pandemic, as that would be really bad luck.

Yet we find ourselves in an unprecedented situation: We have known about the disease in question for a long time, the target population has been identified, and we have a vaccine immediately available. So, we have all the tools and knowledge acquired from the COVID-19 pandemic at our disposal, yet we are choosing to wait and see. We have clearly underestimated the risks of failing after a stalled start to the vaccination campaign.

Question: What exactly are the risks, in your opinion?  Should we already be worried about how the epidemic is progressing?

Dr. Davido: The situation is definitely worrying. I personally am convinced that this disease will be the syphilis of the 21st century. Although the risk is low, it is not beyond the bounds of possibility that this could be the start of a new pandemic. For the time being, its spread is limited to at-risk populations, mainly men who have sex with other men and who have multiple partners, which accounts for around 300,000 people in France. However, the risk for heterosexuals must not be minimized; we must not forget that this disease can also be transmitted through contact with an infected person and by respiratory droplets from people living in the same household. There have been recent cases of women and children infected with monkeypox. If monkeypox starts to spread in the community, rather than being a sexually transmitted infection, the epidemic could spread to the rest of the population. With the rise in cases, scientists are also concerned about transmission to animals. Monkeypox could become endemic like it is in Africa, where rodents are the main reservoir of the virus.

Question: What do we know about the dynamics of this epidemic?  What can be done to effectively improve the situation?

Dr. Davido: Experience gained from African countries affected by monkeypox, as well as from the spate of cases that occurred in the United States in 2003, has shown us that the epidemic can be controlled once the cases have been contained. It is hoped that further waves of the epidemic can be avoided, providing the monkeypox vaccine achieves its objectives.

But we need to give ourselves the means to do so. The expansion of the vaccination program to the most at-risk populations in early July was the right decision. We have seen that ring vaccination targeting close-contact cases does not work with monkeypox. The current problem is that this vaccine is nearly exclusively restricted to hospital settings. We are making the same mistakes as [we did] at the start of the COVID-19 epidemic. We don’t have the right infrastructure in place for this vaccination program. We need to get doctors, paramedics, pharmacists, etc., involved. And cut back on the red tape. After embracing digital procedures during COVID-19, we find ourselves having to complete paper copies of documents for every single person attending a vaccination site. It just doesn’t make sense!

Question: You highlighted the lack of a clear objective with this vaccination campaign. What should we be aiming for?

Dr. Davido: During the COVID-19 vaccination campaign, there was a set number of people to be vaccinated within a given time frame. The approach demanded a fast pace and a desired outcome. Yes, it was an ambitious target from the get-go, but it was one that we stuck to. Currently, no figure, no target, has been set for the monkeypox vaccination program. Ideally, we would have completed the vaccination campaign before the start of the new school year to limit new infections.

As it stands now, only 10% of the target population has received the vaccine. There is talk of the summer period not being favorable. Yet I remember that last year, the COVID-19 vaccination program was strengthened in the middle of August. If the monkeypox vaccination campaign is not given a boost by the end of the summer, we run the risk of encouraging transmission of the virus between close contacts when different groups mix after being on holiday at the start of the new school year. I think that, first and foremost, we must make general practitioners aware of the disease and train them in how to diagnose it so that patients can be isolated and vaccinated as quickly as possible.

Question: There has also been talk of increasing the set 28-day period between the two doses, or even getting rid of it entirely. Would this perhaps lead to better vaccine uptake?

Dr. Davido: The United Kingdom has chosen to give a single dose and recommends a second dose after exposure. I am not sure that this is the best strategy. Although the efficacy data are still limited, the results are not as good after a single dose. According to initial data from the French National Agency for the Safety of Medicines and Health Products (the ANSM), the rate of seroconversion after one dose rises from 10% to 56% on D28 in healthy volunteers, but is between 77% and 89% 2 weeks after the second dose administered on D28.

So, the second dose is needed, especially as immunological memory seems to drop 2 years after the first injection. The U.S. Centers for Disease Control and Prevention proposes leaving 35 days between the two doses. I think this is a reasonable time frame. So, delaying the second dose makes administration of the first dose even easier because the second often fell in the middle of the holiday period and so we also save precious doses. If the time between doses is longer, we risk vaccinated individuals becoming lax and possibly being tempted to skip the “optional” booster or simply forgetting about it.

Question: Are people who have already had the smallpox vaccine better protected against monkeypox?

Dr. Davido: The efficacy of this vaccine against monkeypox is not perfect on a very long-term basis and, to be honest, we don’t really know the level of protection afforded by first-generation vaccines after 20 years. We must not forget that 20% of people infected with monkeypox were vaccinated against smallpox before mandatory vaccination for this disease was abolished [Editor’s note: The requirement of an initial dose of smallpox vaccine was lifted in 1979, once smallpox had been eradicated].

It is hoped that, as a minimum, this vaccine protects against serious illness. Yet in my department, we regularly see severe cases of monkeypox with widespread lesions in the over 45s, who are said to be vaccinated against smallpox.

Question: By comparison, is it likely that a third-generation vaccine would afford better protection against severe illness?

Dr. Davido: We still don’t have enough data or hindsight to assess the real-world impact of third-generation vaccines. This vaccine has a better tolerance profile than its predecessors, but we currently don’t know if it protects against severe forms of monkeypox. We also need to learn more about the disease causing the current epidemic, since it seems different from the sporadic outbreaks that usually crop up in Central and West Africa. The lesions seen are notably milder. The WHO has given this vaccine an efficacy level of 85% against infection by the monkeypox virus, but we must remain cautious: This figure is based on data from Africa. The epidemic in which we find ourselves is not the same. Overall, we must be wary of overly optimistic rhetoric around this new epidemic.

A version of this article appeared on Medscape.com. The article was translated from the Medscape French edition.

PARIS – France is boosting its vaccination campaign in response to the increase in cases of monkeypox. After a sluggish start, newly appointed French health minister François Braun has announced the release of 42,000 vaccine doses. At the same time, medical students will be able to lend a helping hand at vaccination sites. However, some experts have criticized the measures taken as being too lax to combat what the World Health Organization has designated a global health emergency.

For Benjamin Davido, MD, MSc, PhD, an infectious disease specialist at the Raymond-Poincaré Hospital (Paris Public Hospital Trust, AP-HP, Garches region), the risks of this disease have been minimized and the measures taken are not adequate, despite the ready availability of the tools needed to manage the epidemic. We must remain alert to the risks posed by this monkeypox epidemic, which seems different from the sporadic outbreaks that usually crop up in Central and West Africa, he said. Dr. Davido recently shared his opinions in an interview.

Question: What do you think about the monkeypox vaccination campaign currently underway in France?

Dr. Davido: It doesn’t go far enough, and I am surprised by the lack of a concrete and specific objective. The effects of the disease are being minimized, and we seem to be in limbo. It seems we have to wait until the fire is out of control before we can call the fire department. We should have been more reactive and taken a more drastic approach from the get-go. In France, as in other countries affected by this epidemic, we are still, unfortunately, in a phase of observation, reassuring ourselves that this will surely not become another pandemic, as that would be really bad luck.

Yet we find ourselves in an unprecedented situation: We have known about the disease in question for a long time, the target population has been identified, and we have a vaccine immediately available. So, we have all the tools and knowledge acquired from the COVID-19 pandemic at our disposal, yet we are choosing to wait and see. We have clearly underestimated the risks of failing after a stalled start to the vaccination campaign.

Question: What exactly are the risks, in your opinion?  Should we already be worried about how the epidemic is progressing?

Dr. Davido: The situation is definitely worrying. I personally am convinced that this disease will be the syphilis of the 21st century. Although the risk is low, it is not beyond the bounds of possibility that this could be the start of a new pandemic. For the time being, its spread is limited to at-risk populations, mainly men who have sex with other men and who have multiple partners, which accounts for around 300,000 people in France. However, the risk for heterosexuals must not be minimized; we must not forget that this disease can also be transmitted through contact with an infected person and by respiratory droplets from people living in the same household. There have been recent cases of women and children infected with monkeypox. If monkeypox starts to spread in the community, rather than being a sexually transmitted infection, the epidemic could spread to the rest of the population. With the rise in cases, scientists are also concerned about transmission to animals. Monkeypox could become endemic like it is in Africa, where rodents are the main reservoir of the virus.

Question: What do we know about the dynamics of this epidemic?  What can be done to effectively improve the situation?

Dr. Davido: Experience gained from African countries affected by monkeypox, as well as from the spate of cases that occurred in the United States in 2003, has shown us that the epidemic can be controlled once the cases have been contained. It is hoped that further waves of the epidemic can be avoided, providing the monkeypox vaccine achieves its objectives.

But we need to give ourselves the means to do so. The expansion of the vaccination program to the most at-risk populations in early July was the right decision. We have seen that ring vaccination targeting close-contact cases does not work with monkeypox. The current problem is that this vaccine is nearly exclusively restricted to hospital settings. We are making the same mistakes as [we did] at the start of the COVID-19 epidemic. We don’t have the right infrastructure in place for this vaccination program. We need to get doctors, paramedics, pharmacists, etc., involved. And cut back on the red tape. After embracing digital procedures during COVID-19, we find ourselves having to complete paper copies of documents for every single person attending a vaccination site. It just doesn’t make sense!

Question: You highlighted the lack of a clear objective with this vaccination campaign. What should we be aiming for?

Dr. Davido: During the COVID-19 vaccination campaign, there was a set number of people to be vaccinated within a given time frame. The approach demanded a fast pace and a desired outcome. Yes, it was an ambitious target from the get-go, but it was one that we stuck to. Currently, no figure, no target, has been set for the monkeypox vaccination program. Ideally, we would have completed the vaccination campaign before the start of the new school year to limit new infections.

As it stands now, only 10% of the target population has received the vaccine. There is talk of the summer period not being favorable. Yet I remember that last year, the COVID-19 vaccination program was strengthened in the middle of August. If the monkeypox vaccination campaign is not given a boost by the end of the summer, we run the risk of encouraging transmission of the virus between close contacts when different groups mix after being on holiday at the start of the new school year. I think that, first and foremost, we must make general practitioners aware of the disease and train them in how to diagnose it so that patients can be isolated and vaccinated as quickly as possible.

Question: There has also been talk of increasing the set 28-day period between the two doses, or even getting rid of it entirely. Would this perhaps lead to better vaccine uptake?

Dr. Davido: The United Kingdom has chosen to give a single dose and recommends a second dose after exposure. I am not sure that this is the best strategy. Although the efficacy data are still limited, the results are not as good after a single dose. According to initial data from the French National Agency for the Safety of Medicines and Health Products (the ANSM), the rate of seroconversion after one dose rises from 10% to 56% on D28 in healthy volunteers, but is between 77% and 89% 2 weeks after the second dose administered on D28.

So, the second dose is needed, especially as immunological memory seems to drop 2 years after the first injection. The U.S. Centers for Disease Control and Prevention proposes leaving 35 days between the two doses. I think this is a reasonable time frame. So, delaying the second dose makes administration of the first dose even easier because the second often fell in the middle of the holiday period and so we also save precious doses. If the time between doses is longer, we risk vaccinated individuals becoming lax and possibly being tempted to skip the “optional” booster or simply forgetting about it.

Question: Are people who have already had the smallpox vaccine better protected against monkeypox?

Dr. Davido: The efficacy of this vaccine against monkeypox is not perfect on a very long-term basis and, to be honest, we don’t really know the level of protection afforded by first-generation vaccines after 20 years. We must not forget that 20% of people infected with monkeypox were vaccinated against smallpox before mandatory vaccination for this disease was abolished [Editor’s note: The requirement of an initial dose of smallpox vaccine was lifted in 1979, once smallpox had been eradicated].

It is hoped that, as a minimum, this vaccine protects against serious illness. Yet in my department, we regularly see severe cases of monkeypox with widespread lesions in the over 45s, who are said to be vaccinated against smallpox.

Question: By comparison, is it likely that a third-generation vaccine would afford better protection against severe illness?

Dr. Davido: We still don’t have enough data or hindsight to assess the real-world impact of third-generation vaccines. This vaccine has a better tolerance profile than its predecessors, but we currently don’t know if it protects against severe forms of monkeypox. We also need to learn more about the disease causing the current epidemic, since it seems different from the sporadic outbreaks that usually crop up in Central and West Africa. The lesions seen are notably milder. The WHO has given this vaccine an efficacy level of 85% against infection by the monkeypox virus, but we must remain cautious: This figure is based on data from Africa. The epidemic in which we find ourselves is not the same. Overall, we must be wary of overly optimistic rhetoric around this new epidemic.

A version of this article appeared on Medscape.com. The article was translated from the Medscape French edition.

PARIS – France is boosting its vaccination campaign in response to the increase in cases of monkeypox. After a sluggish start, newly appointed French health minister François Braun has announced the release of 42,000 vaccine doses. At the same time, medical students will be able to lend a helping hand at vaccination sites. However, some experts have criticized the measures taken as being too lax to combat what the World Health Organization has designated a global health emergency.

For Benjamin Davido, MD, MSc, PhD, an infectious disease specialist at the Raymond-Poincaré Hospital (Paris Public Hospital Trust, AP-HP, Garches region), the risks of this disease have been minimized and the measures taken are not adequate, despite the ready availability of the tools needed to manage the epidemic. We must remain alert to the risks posed by this monkeypox epidemic, which seems different from the sporadic outbreaks that usually crop up in Central and West Africa, he said. Dr. Davido recently shared his opinions in an interview.

Question: What do you think about the monkeypox vaccination campaign currently underway in France?

Dr. Davido: It doesn’t go far enough, and I am surprised by the lack of a concrete and specific objective. The effects of the disease are being minimized, and we seem to be in limbo. It seems we have to wait until the fire is out of control before we can call the fire department. We should have been more reactive and taken a more drastic approach from the get-go. In France, as in other countries affected by this epidemic, we are still, unfortunately, in a phase of observation, reassuring ourselves that this will surely not become another pandemic, as that would be really bad luck.

Yet we find ourselves in an unprecedented situation: We have known about the disease in question for a long time, the target population has been identified, and we have a vaccine immediately available. So, we have all the tools and knowledge acquired from the COVID-19 pandemic at our disposal, yet we are choosing to wait and see. We have clearly underestimated the risks of failing after a stalled start to the vaccination campaign.

Question: What exactly are the risks, in your opinion?  Should we already be worried about how the epidemic is progressing?

Dr. Davido: The situation is definitely worrying. I personally am convinced that this disease will be the syphilis of the 21st century. Although the risk is low, it is not beyond the bounds of possibility that this could be the start of a new pandemic. For the time being, its spread is limited to at-risk populations, mainly men who have sex with other men and who have multiple partners, which accounts for around 300,000 people in France. However, the risk for heterosexuals must not be minimized; we must not forget that this disease can also be transmitted through contact with an infected person and by respiratory droplets from people living in the same household. There have been recent cases of women and children infected with monkeypox. If monkeypox starts to spread in the community, rather than being a sexually transmitted infection, the epidemic could spread to the rest of the population. With the rise in cases, scientists are also concerned about transmission to animals. Monkeypox could become endemic like it is in Africa, where rodents are the main reservoir of the virus.

Question: What do we know about the dynamics of this epidemic?  What can be done to effectively improve the situation?

Dr. Davido: Experience gained from African countries affected by monkeypox, as well as from the spate of cases that occurred in the United States in 2003, has shown us that the epidemic can be controlled once the cases have been contained. It is hoped that further waves of the epidemic can be avoided, providing the monkeypox vaccine achieves its objectives.

But we need to give ourselves the means to do so. The expansion of the vaccination program to the most at-risk populations in early July was the right decision. We have seen that ring vaccination targeting close-contact cases does not work with monkeypox. The current problem is that this vaccine is nearly exclusively restricted to hospital settings. We are making the same mistakes as [we did] at the start of the COVID-19 epidemic. We don’t have the right infrastructure in place for this vaccination program. We need to get doctors, paramedics, pharmacists, etc., involved. And cut back on the red tape. After embracing digital procedures during COVID-19, we find ourselves having to complete paper copies of documents for every single person attending a vaccination site. It just doesn’t make sense!

Question: You highlighted the lack of a clear objective with this vaccination campaign. What should we be aiming for?

Dr. Davido: During the COVID-19 vaccination campaign, there was a set number of people to be vaccinated within a given time frame. The approach demanded a fast pace and a desired outcome. Yes, it was an ambitious target from the get-go, but it was one that we stuck to. Currently, no figure, no target, has been set for the monkeypox vaccination program. Ideally, we would have completed the vaccination campaign before the start of the new school year to limit new infections.

As it stands now, only 10% of the target population has received the vaccine. There is talk of the summer period not being favorable. Yet I remember that last year, the COVID-19 vaccination program was strengthened in the middle of August. If the monkeypox vaccination campaign is not given a boost by the end of the summer, we run the risk of encouraging transmission of the virus between close contacts when different groups mix after being on holiday at the start of the new school year. I think that, first and foremost, we must make general practitioners aware of the disease and train them in how to diagnose it so that patients can be isolated and vaccinated as quickly as possible.

Question: There has also been talk of increasing the set 28-day period between the two doses, or even getting rid of it entirely. Would this perhaps lead to better vaccine uptake?

Dr. Davido: The United Kingdom has chosen to give a single dose and recommends a second dose after exposure. I am not sure that this is the best strategy. Although the efficacy data are still limited, the results are not as good after a single dose. According to initial data from the French National Agency for the Safety of Medicines and Health Products (the ANSM), the rate of seroconversion after one dose rises from 10% to 56% on D28 in healthy volunteers, but is between 77% and 89% 2 weeks after the second dose administered on D28.

So, the second dose is needed, especially as immunological memory seems to drop 2 years after the first injection. The U.S. Centers for Disease Control and Prevention proposes leaving 35 days between the two doses. I think this is a reasonable time frame. So, delaying the second dose makes administration of the first dose even easier because the second often fell in the middle of the holiday period and so we also save precious doses. If the time between doses is longer, we risk vaccinated individuals becoming lax and possibly being tempted to skip the “optional” booster or simply forgetting about it.

Question: Are people who have already had the smallpox vaccine better protected against monkeypox?

Dr. Davido: The efficacy of this vaccine against monkeypox is not perfect on a very long-term basis and, to be honest, we don’t really know the level of protection afforded by first-generation vaccines after 20 years. We must not forget that 20% of people infected with monkeypox were vaccinated against smallpox before mandatory vaccination for this disease was abolished [Editor’s note: The requirement of an initial dose of smallpox vaccine was lifted in 1979, once smallpox had been eradicated].

It is hoped that, as a minimum, this vaccine protects against serious illness. Yet in my department, we regularly see severe cases of monkeypox with widespread lesions in the over 45s, who are said to be vaccinated against smallpox.

Question: By comparison, is it likely that a third-generation vaccine would afford better protection against severe illness?

Dr. Davido: We still don’t have enough data or hindsight to assess the real-world impact of third-generation vaccines. This vaccine has a better tolerance profile than its predecessors, but we currently don’t know if it protects against severe forms of monkeypox. We also need to learn more about the disease causing the current epidemic, since it seems different from the sporadic outbreaks that usually crop up in Central and West Africa. The lesions seen are notably milder. The WHO has given this vaccine an efficacy level of 85% against infection by the monkeypox virus, but we must remain cautious: This figure is based on data from Africa. The epidemic in which we find ourselves is not the same. Overall, we must be wary of overly optimistic rhetoric around this new epidemic.

A version of this article appeared on Medscape.com. The article was translated from the Medscape French edition.

Thursday night

It was 9 o’clock at night when my phone rang. I didn’t recognize the number but decided to answer it anyway. It was my doctor.

“Chase, I got your labs back and you have a critically low level. I spoke with someone at the hospital, I think I know what is happening, but I need you to go to the pharmacy right now and get a medicine.” She explained further and as I listened electric currents ran through my thighs until I could barely feel my legs.

“I’m so sorry, Chase. I missed it. It was low the last time we did your labs 9 months ago, and I missed it.”

In disbelief, I continued to listen as she instructed me about the next steps I was to take and prepared me for what was to come the next day.

“If you notice any changes overnight, go straight to the ED.”

My chest tingled and I could barely breathe. My mind struggled to comprehend what was happening. I looked at my husband sitting close by on the couch. He looked concerned. I tuned back in and heard her say: “Is your husband there? Can I talk to him?”

“Yes,” is all I could manage, and I handed him the phone. I sat while he listened and asked his questions. My breathing came back under my control, my legs felt wiry, and restlessness set in. “I have to get out of here,” I thought. “I have to go and pick up this medicine.”
 

Monday afternoon

I am sitting across from a PGY3 resident I have been treating since his intern year, as part of his treatment plan for managing a chronic mental illness that began in medical school. Earlier in the day, I received an urgent message from him requesting an emergency appointment.

Within a few minutes of sitting down, the story from his weekend call shift tumbled out of him. His speech became pressured, and his eyes welled with tears as he recounted in detail the steps he had taken to care for a very sick patient overnight.

“I missed it.” The dam broke and he sat sobbing in front of me, his body trembling.

I sat silently across from him. Willing him to breathe.

In time, his breathing came back under his control, and he slowly regained his composure. He continued: “I got the imaging, and I missed a bleed.”
 

Failure and shame

I can recall memorable moments from my training when I came to understand that what I initially perceived to be a mistake was instead part of the work. An example from our practice involves a patient whom I was comanaging with her primary care provider (PCP). She was not doing well following a critical work event. When I met with her after the event, she admitted having thoughts of suicide, refused a voluntary inpatient admission, and would not have met criteria for an involuntary admission. My hands were tied.

Together we created a plan to keep her safe, which included paging her PCP after hours if needed. I told her PCP before leaving that night that he might hear from her and that if she reached out, she would require hospitalization.

I arrived at work the following day, and her PCP shared with me that our patient had overdosed on medication, paged him, and was admitted to the unit.

He seemed forlorn.

I was both relieved by the news and confused by his reaction. I had hoped that she would choose a higher level of care than what we could provide her as an outpatient. I said: “This is good. She followed the plan.”

Her overdose was, of course, not part of the plan. She was struggling with several internal conflicts, including having mixed feelings about coming into the hospital; but, when the critical moment happened and she was faced with a decision to call for help or possibly die, she chose to call her PCP and have him paged as we had talked about.

I looked at her PCP. “You helped get her to where she needed to be.”

In the years of working side by side with medically trained colleagues, I have time and again needed to reframe for them that what they perceive to be a “failure” or a “crisis” is often a catalyst for change. The patient I comanaged with the PCP was a highly skilled caregiver and, as such, had been having a hard time asking for help. The hospitalization that her PCP facilitated allowed her to receive the care she needed and created an opportunity for family and friends to show up for her. Their support fed her, and she only made gains from that point on.

My training had taught me that respecting a patient’s autonomy was of the utmost importance. This instills confidence in patients as the authority in their lives. For a clinician to do this, a certain amount of helplessness must be tolerated. As I became better at identifying these moments of helplessness, feelings of failure and shame transformed.
 

Medical error

Sitting across from the PGY3 resident who I had met with weekly for the past 3 years, I thought about his error.

I thought about my phone call 4 nights earlier. My doctor was called at home by a lab technician, who never met their patients but was simply following protocol and alerted my doctor to the worsening number that she should have been aware of 9 months earlier.

Just like my doctor’s lapse of attention, my patient’s error was not a moment of helplessness to be tolerated. These were mistakes, and there was no way around it.

“People make mistakes.” I said simply.

We sat silently for a time.

I don’t remember who broke the silence. The conversation that followed was centered on our humanity and our capability for both compassion and fallibility. Afterward, I wondered who my doctor confided in and hoped she had a similar conversation.

Dr. Levesque is a clinical psychologist and clinical assistant professor of psychiatry at the Geisel School of Medicine at Dartmouth, Hanover, N.H., where she also serves on the Committee for a Respectful Learning Environment.

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

Thursday night

It was 9 o’clock at night when my phone rang. I didn’t recognize the number but decided to answer it anyway. It was my doctor.

“Chase, I got your labs back and you have a critically low level. I spoke with someone at the hospital, I think I know what is happening, but I need you to go to the pharmacy right now and get a medicine.” She explained further and as I listened electric currents ran through my thighs until I could barely feel my legs.

“I’m so sorry, Chase. I missed it. It was low the last time we did your labs 9 months ago, and I missed it.”

In disbelief, I continued to listen as she instructed me about the next steps I was to take and prepared me for what was to come the next day.

“If you notice any changes overnight, go straight to the ED.”

My chest tingled and I could barely breathe. My mind struggled to comprehend what was happening. I looked at my husband sitting close by on the couch. He looked concerned. I tuned back in and heard her say: “Is your husband there? Can I talk to him?”

“Yes,” is all I could manage, and I handed him the phone. I sat while he listened and asked his questions. My breathing came back under my control, my legs felt wiry, and restlessness set in. “I have to get out of here,” I thought. “I have to go and pick up this medicine.”
 

Monday afternoon

I am sitting across from a PGY3 resident I have been treating since his intern year, as part of his treatment plan for managing a chronic mental illness that began in medical school. Earlier in the day, I received an urgent message from him requesting an emergency appointment.

Within a few minutes of sitting down, the story from his weekend call shift tumbled out of him. His speech became pressured, and his eyes welled with tears as he recounted in detail the steps he had taken to care for a very sick patient overnight.

“I missed it.” The dam broke and he sat sobbing in front of me, his body trembling.

I sat silently across from him. Willing him to breathe.

In time, his breathing came back under his control, and he slowly regained his composure. He continued: “I got the imaging, and I missed a bleed.”
 

Failure and shame

I can recall memorable moments from my training when I came to understand that what I initially perceived to be a mistake was instead part of the work. An example from our practice involves a patient whom I was comanaging with her primary care provider (PCP). She was not doing well following a critical work event. When I met with her after the event, she admitted having thoughts of suicide, refused a voluntary inpatient admission, and would not have met criteria for an involuntary admission. My hands were tied.

Together we created a plan to keep her safe, which included paging her PCP after hours if needed. I told her PCP before leaving that night that he might hear from her and that if she reached out, she would require hospitalization.

I arrived at work the following day, and her PCP shared with me that our patient had overdosed on medication, paged him, and was admitted to the unit.

He seemed forlorn.

I was both relieved by the news and confused by his reaction. I had hoped that she would choose a higher level of care than what we could provide her as an outpatient. I said: “This is good. She followed the plan.”

Her overdose was, of course, not part of the plan. She was struggling with several internal conflicts, including having mixed feelings about coming into the hospital; but, when the critical moment happened and she was faced with a decision to call for help or possibly die, she chose to call her PCP and have him paged as we had talked about.

I looked at her PCP. “You helped get her to where she needed to be.”

In the years of working side by side with medically trained colleagues, I have time and again needed to reframe for them that what they perceive to be a “failure” or a “crisis” is often a catalyst for change. The patient I comanaged with the PCP was a highly skilled caregiver and, as such, had been having a hard time asking for help. The hospitalization that her PCP facilitated allowed her to receive the care she needed and created an opportunity for family and friends to show up for her. Their support fed her, and she only made gains from that point on.

My training had taught me that respecting a patient’s autonomy was of the utmost importance. This instills confidence in patients as the authority in their lives. For a clinician to do this, a certain amount of helplessness must be tolerated. As I became better at identifying these moments of helplessness, feelings of failure and shame transformed.
 

Medical error

Sitting across from the PGY3 resident who I had met with weekly for the past 3 years, I thought about his error.

I thought about my phone call 4 nights earlier. My doctor was called at home by a lab technician, who never met their patients but was simply following protocol and alerted my doctor to the worsening number that she should have been aware of 9 months earlier.

Just like my doctor’s lapse of attention, my patient’s error was not a moment of helplessness to be tolerated. These were mistakes, and there was no way around it.

“People make mistakes.” I said simply.

We sat silently for a time.

I don’t remember who broke the silence. The conversation that followed was centered on our humanity and our capability for both compassion and fallibility. Afterward, I wondered who my doctor confided in and hoped she had a similar conversation.

Dr. Levesque is a clinical psychologist and clinical assistant professor of psychiatry at the Geisel School of Medicine at Dartmouth, Hanover, N.H., where she also serves on the Committee for a Respectful Learning Environment.

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

Thursday night

It was 9 o’clock at night when my phone rang. I didn’t recognize the number but decided to answer it anyway. It was my doctor.

“Chase, I got your labs back and you have a critically low level. I spoke with someone at the hospital, I think I know what is happening, but I need you to go to the pharmacy right now and get a medicine.” She explained further and as I listened electric currents ran through my thighs until I could barely feel my legs.

“I’m so sorry, Chase. I missed it. It was low the last time we did your labs 9 months ago, and I missed it.”

In disbelief, I continued to listen as she instructed me about the next steps I was to take and prepared me for what was to come the next day.

“If you notice any changes overnight, go straight to the ED.”

My chest tingled and I could barely breathe. My mind struggled to comprehend what was happening. I looked at my husband sitting close by on the couch. He looked concerned. I tuned back in and heard her say: “Is your husband there? Can I talk to him?”

“Yes,” is all I could manage, and I handed him the phone. I sat while he listened and asked his questions. My breathing came back under my control, my legs felt wiry, and restlessness set in. “I have to get out of here,” I thought. “I have to go and pick up this medicine.”
 

Monday afternoon

I am sitting across from a PGY3 resident I have been treating since his intern year, as part of his treatment plan for managing a chronic mental illness that began in medical school. Earlier in the day, I received an urgent message from him requesting an emergency appointment.

Within a few minutes of sitting down, the story from his weekend call shift tumbled out of him. His speech became pressured, and his eyes welled with tears as he recounted in detail the steps he had taken to care for a very sick patient overnight.

“I missed it.” The dam broke and he sat sobbing in front of me, his body trembling.

I sat silently across from him. Willing him to breathe.

In time, his breathing came back under his control, and he slowly regained his composure. He continued: “I got the imaging, and I missed a bleed.”
 

Failure and shame

I can recall memorable moments from my training when I came to understand that what I initially perceived to be a mistake was instead part of the work. An example from our practice involves a patient whom I was comanaging with her primary care provider (PCP). She was not doing well following a critical work event. When I met with her after the event, she admitted having thoughts of suicide, refused a voluntary inpatient admission, and would not have met criteria for an involuntary admission. My hands were tied.

Together we created a plan to keep her safe, which included paging her PCP after hours if needed. I told her PCP before leaving that night that he might hear from her and that if she reached out, she would require hospitalization.

I arrived at work the following day, and her PCP shared with me that our patient had overdosed on medication, paged him, and was admitted to the unit.

He seemed forlorn.

I was both relieved by the news and confused by his reaction. I had hoped that she would choose a higher level of care than what we could provide her as an outpatient. I said: “This is good. She followed the plan.”

Her overdose was, of course, not part of the plan. She was struggling with several internal conflicts, including having mixed feelings about coming into the hospital; but, when the critical moment happened and she was faced with a decision to call for help or possibly die, she chose to call her PCP and have him paged as we had talked about.

I looked at her PCP. “You helped get her to where she needed to be.”

In the years of working side by side with medically trained colleagues, I have time and again needed to reframe for them that what they perceive to be a “failure” or a “crisis” is often a catalyst for change. The patient I comanaged with the PCP was a highly skilled caregiver and, as such, had been having a hard time asking for help. The hospitalization that her PCP facilitated allowed her to receive the care she needed and created an opportunity for family and friends to show up for her. Their support fed her, and she only made gains from that point on.

My training had taught me that respecting a patient’s autonomy was of the utmost importance. This instills confidence in patients as the authority in their lives. For a clinician to do this, a certain amount of helplessness must be tolerated. As I became better at identifying these moments of helplessness, feelings of failure and shame transformed.
 

Medical error

Sitting across from the PGY3 resident who I had met with weekly for the past 3 years, I thought about his error.

I thought about my phone call 4 nights earlier. My doctor was called at home by a lab technician, who never met their patients but was simply following protocol and alerted my doctor to the worsening number that she should have been aware of 9 months earlier.

Just like my doctor’s lapse of attention, my patient’s error was not a moment of helplessness to be tolerated. These were mistakes, and there was no way around it.

“People make mistakes.” I said simply.

We sat silently for a time.

I don’t remember who broke the silence. The conversation that followed was centered on our humanity and our capability for both compassion and fallibility. Afterward, I wondered who my doctor confided in and hoped she had a similar conversation.

Dr. Levesque is a clinical psychologist and clinical assistant professor of psychiatry at the Geisel School of Medicine at Dartmouth, Hanover, N.H., where she also serves on the Committee for a Respectful Learning Environment.

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

New research suggests that regular physical activity can help lower the risk of COVID-19 infection and its severity, with a weekly tally of 150 minutes of moderate, or 75 minutes of vigorous, physical activity affording the best protection.

“Our findings highlight the protective effects of engaging in sufficient physical activity as a public health strategy, with potential benefits to reduce the risk of severe COVID-19,” say Antonio García-Hermoso, PhD, Public University of Navarra, Pamplona, Spain, and colleagues.

“Regular physical activity seemed to be related to a lower risk of COVID-19 infection, Dr. García-Hermoso said in an interview. “There is evidence that regular physical activity might contribute to a more effective immune response, providing enhanced protective immunity to infections, which could explain the relationship between exercise consistency with COVID-19 infection.”

Regular exercise may also help to boost the body’s anti-inflammatory responses, as well as cardiorespiratory and muscular fitness, all of which may explain its beneficial effects on COVID-19 severity, the researchers say.

The study was published online in the British Journal of Sports Medicine.
 

Strong protection from COVID?

A growing body of evidence suggests that increased physical activity may modulate the course of COVID-19 infection and reduce the risk of poor outcomes. The new analysis is the first to systematically evaluate and pool data on the effect of regular physical activity on COVID-19 outcomes.

The findings are based on data from 16 studies with over 1.8 million adults (53% women, mean age 53 years).

Individuals who included regular physical activity in their weekly routine had an 11% lower risk for infection with SARS-CoV-2 (hazard ratio, 0.89; 95% confidence interval, 0.84-0.95), compared with inactive peers.

The physically active adults also had a 36% (HR, 0.64; 95% CI, 0.54-0.76) lower risk of being hospitalized, a 44% (HR, 0.66; 95% CI, 0.58-0.77) lower risk for severe COVID-19 illness, and a 43% (HR, 0.57; 95% CI, 0.46-0.71) lower risk of dying from COVID-19 than their inactive peers.

The greatest protective effect occurs with achieving at least 500 metabolic equivalent of task (MET) minutes per week of physical activity – equivalent to 150 minutes of moderate-intensity or 75 min of vigorous-intensity physical activity per week – with no added benefit beyond this level.

The researchers caution that the analysis included observational studies, differing study designs, subjective assessments of physical activity levels, and concerned only the Beta and Delta variants of SARS-CoV-2, not Omicron.

Despite these limitations, the researchers say their findings “may help guide physicians and health care policymakers in making recommendations and developing guidelines with respect to the degree of physical activity that can help reduce the risk of infectivity, hospitalization, severity, and mortality of COVID-19 at both the individual and the population level, especially in high-risk patients.”
 

Helpful, but not a panacea

Reached for comment, Sean Heffron, MD, a preventive cardiologist and assistant professor of medicine at NYU Langone Health, New York, said the study “supports the well-established nonlinear association of increasing physical activity with adverse outcomes from a diverse array of diseases, including infectious diseases, such as COVID-19.”

The observation is not particularly surprising, he said.

“It is as I would suspect. They compiled data from a large number of studies published over the past several years that all had consistent findings,” Dr. Heffron said.

“The take-away from a public health standpoint is that being physically active improves health in myriad ways. That being said, it is not a panacea, so additional measures (masking, vaccinations, etc.) are important for everyone,” he said.

Also weighing in, Joseph Herrera, DO, chair of the department of rehabilitation for Mount Sinai Health System, New York, said, “If you are physically fit, your body is more resilient and better prepared to handle the stressors of COVID or any other disease process.”

For now, however, the question of whether physical fitness is actually protective against COVID remains unclear. “I’m just not sure right now,” Dr. Herrera said in an interview.

He said he has treated athletes in professional sports – including the National Football League and Major League Baseball – and some of them have had long COVID and have not returned to play. “These are athletes at the peak of fitness and their career.”

Nonetheless, Dr. Herrera said a good public health message in general is to stay fit or get fit.

“That’s something I preach all the time,” he told this news organization.

Dr. García-Hermoso agreed. “In contrast to the vast majority of drugs, exercise is free of adverse effects. It’s time to consider exercise as medicine. It’s never too late to start being physically active.”

The study had no specific funding. Dr. García-Hermoso, Dr. Heffron, and Dr. Herrera have reported no relevant financial relationships.

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

New research suggests that regular physical activity can help lower the risk of COVID-19 infection and its severity, with a weekly tally of 150 minutes of moderate, or 75 minutes of vigorous, physical activity affording the best protection.

“Our findings highlight the protective effects of engaging in sufficient physical activity as a public health strategy, with potential benefits to reduce the risk of severe COVID-19,” say Antonio García-Hermoso, PhD, Public University of Navarra, Pamplona, Spain, and colleagues.

“Regular physical activity seemed to be related to a lower risk of COVID-19 infection, Dr. García-Hermoso said in an interview. “There is evidence that regular physical activity might contribute to a more effective immune response, providing enhanced protective immunity to infections, which could explain the relationship between exercise consistency with COVID-19 infection.”

Regular exercise may also help to boost the body’s anti-inflammatory responses, as well as cardiorespiratory and muscular fitness, all of which may explain its beneficial effects on COVID-19 severity, the researchers say.

The study was published online in the British Journal of Sports Medicine.
 

Strong protection from COVID?

A growing body of evidence suggests that increased physical activity may modulate the course of COVID-19 infection and reduce the risk of poor outcomes. The new analysis is the first to systematically evaluate and pool data on the effect of regular physical activity on COVID-19 outcomes.

The findings are based on data from 16 studies with over 1.8 million adults (53% women, mean age 53 years).

Individuals who included regular physical activity in their weekly routine had an 11% lower risk for infection with SARS-CoV-2 (hazard ratio, 0.89; 95% confidence interval, 0.84-0.95), compared with inactive peers.

The physically active adults also had a 36% (HR, 0.64; 95% CI, 0.54-0.76) lower risk of being hospitalized, a 44% (HR, 0.66; 95% CI, 0.58-0.77) lower risk for severe COVID-19 illness, and a 43% (HR, 0.57; 95% CI, 0.46-0.71) lower risk of dying from COVID-19 than their inactive peers.

The greatest protective effect occurs with achieving at least 500 metabolic equivalent of task (MET) minutes per week of physical activity – equivalent to 150 minutes of moderate-intensity or 75 min of vigorous-intensity physical activity per week – with no added benefit beyond this level.

The researchers caution that the analysis included observational studies, differing study designs, subjective assessments of physical activity levels, and concerned only the Beta and Delta variants of SARS-CoV-2, not Omicron.

Despite these limitations, the researchers say their findings “may help guide physicians and health care policymakers in making recommendations and developing guidelines with respect to the degree of physical activity that can help reduce the risk of infectivity, hospitalization, severity, and mortality of COVID-19 at both the individual and the population level, especially in high-risk patients.”
 

Helpful, but not a panacea

Reached for comment, Sean Heffron, MD, a preventive cardiologist and assistant professor of medicine at NYU Langone Health, New York, said the study “supports the well-established nonlinear association of increasing physical activity with adverse outcomes from a diverse array of diseases, including infectious diseases, such as COVID-19.”

The observation is not particularly surprising, he said.

“It is as I would suspect. They compiled data from a large number of studies published over the past several years that all had consistent findings,” Dr. Heffron said.

“The take-away from a public health standpoint is that being physically active improves health in myriad ways. That being said, it is not a panacea, so additional measures (masking, vaccinations, etc.) are important for everyone,” he said.

Also weighing in, Joseph Herrera, DO, chair of the department of rehabilitation for Mount Sinai Health System, New York, said, “If you are physically fit, your body is more resilient and better prepared to handle the stressors of COVID or any other disease process.”

For now, however, the question of whether physical fitness is actually protective against COVID remains unclear. “I’m just not sure right now,” Dr. Herrera said in an interview.

He said he has treated athletes in professional sports – including the National Football League and Major League Baseball – and some of them have had long COVID and have not returned to play. “These are athletes at the peak of fitness and their career.”

Nonetheless, Dr. Herrera said a good public health message in general is to stay fit or get fit.

“That’s something I preach all the time,” he told this news organization.

Dr. García-Hermoso agreed. “In contrast to the vast majority of drugs, exercise is free of adverse effects. It’s time to consider exercise as medicine. It’s never too late to start being physically active.”

The study had no specific funding. Dr. García-Hermoso, Dr. Heffron, and Dr. Herrera have reported no relevant financial relationships.

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

New research suggests that regular physical activity can help lower the risk of COVID-19 infection and its severity, with a weekly tally of 150 minutes of moderate, or 75 minutes of vigorous, physical activity affording the best protection.

“Our findings highlight the protective effects of engaging in sufficient physical activity as a public health strategy, with potential benefits to reduce the risk of severe COVID-19,” say Antonio García-Hermoso, PhD, Public University of Navarra, Pamplona, Spain, and colleagues.

“Regular physical activity seemed to be related to a lower risk of COVID-19 infection, Dr. García-Hermoso said in an interview. “There is evidence that regular physical activity might contribute to a more effective immune response, providing enhanced protective immunity to infections, which could explain the relationship between exercise consistency with COVID-19 infection.”

Regular exercise may also help to boost the body’s anti-inflammatory responses, as well as cardiorespiratory and muscular fitness, all of which may explain its beneficial effects on COVID-19 severity, the researchers say.

The study was published online in the British Journal of Sports Medicine.
 

Strong protection from COVID?

A growing body of evidence suggests that increased physical activity may modulate the course of COVID-19 infection and reduce the risk of poor outcomes. The new analysis is the first to systematically evaluate and pool data on the effect of regular physical activity on COVID-19 outcomes.

The findings are based on data from 16 studies with over 1.8 million adults (53% women, mean age 53 years).

Individuals who included regular physical activity in their weekly routine had an 11% lower risk for infection with SARS-CoV-2 (hazard ratio, 0.89; 95% confidence interval, 0.84-0.95), compared with inactive peers.

The physically active adults also had a 36% (HR, 0.64; 95% CI, 0.54-0.76) lower risk of being hospitalized, a 44% (HR, 0.66; 95% CI, 0.58-0.77) lower risk for severe COVID-19 illness, and a 43% (HR, 0.57; 95% CI, 0.46-0.71) lower risk of dying from COVID-19 than their inactive peers.

The greatest protective effect occurs with achieving at least 500 metabolic equivalent of task (MET) minutes per week of physical activity – equivalent to 150 minutes of moderate-intensity or 75 min of vigorous-intensity physical activity per week – with no added benefit beyond this level.

The researchers caution that the analysis included observational studies, differing study designs, subjective assessments of physical activity levels, and concerned only the Beta and Delta variants of SARS-CoV-2, not Omicron.

Despite these limitations, the researchers say their findings “may help guide physicians and health care policymakers in making recommendations and developing guidelines with respect to the degree of physical activity that can help reduce the risk of infectivity, hospitalization, severity, and mortality of COVID-19 at both the individual and the population level, especially in high-risk patients.”
 

Helpful, but not a panacea

Reached for comment, Sean Heffron, MD, a preventive cardiologist and assistant professor of medicine at NYU Langone Health, New York, said the study “supports the well-established nonlinear association of increasing physical activity with adverse outcomes from a diverse array of diseases, including infectious diseases, such as COVID-19.”

The observation is not particularly surprising, he said.

“It is as I would suspect. They compiled data from a large number of studies published over the past several years that all had consistent findings,” Dr. Heffron said.

“The take-away from a public health standpoint is that being physically active improves health in myriad ways. That being said, it is not a panacea, so additional measures (masking, vaccinations, etc.) are important for everyone,” he said.

Also weighing in, Joseph Herrera, DO, chair of the department of rehabilitation for Mount Sinai Health System, New York, said, “If you are physically fit, your body is more resilient and better prepared to handle the stressors of COVID or any other disease process.”

For now, however, the question of whether physical fitness is actually protective against COVID remains unclear. “I’m just not sure right now,” Dr. Herrera said in an interview.

He said he has treated athletes in professional sports – including the National Football League and Major League Baseball – and some of them have had long COVID and have not returned to play. “These are athletes at the peak of fitness and their career.”

Nonetheless, Dr. Herrera said a good public health message in general is to stay fit or get fit.

“That’s something I preach all the time,” he told this news organization.

Dr. García-Hermoso agreed. “In contrast to the vast majority of drugs, exercise is free of adverse effects. It’s time to consider exercise as medicine. It’s never too late to start being physically active.”

The study had no specific funding. Dr. García-Hermoso, Dr. Heffron, and Dr. Herrera have reported no relevant financial relationships.

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

Liver transplantation has the opportunity to cure both localized HCC as well as underlying liver cirrhosis. Donor organ shortage has led to the implementation of the Milan criteria as a way to identify patients whose tumor burden is low enough to predict a good outcome. Downstaging liver cancer to fit within Milan criteria has been controversial.

Tabrizian and colleagues undertook a retrospective cohort analysis of 2645 adult patients with HCC who underwent liver transplant. Out of those, 2122 patients always had disease that was within the Milan criteria, 341 patients had HCC that was downstaged to fit within the Milan criteria, and 182 patients had HCC that was outside the Milan criteria at the time of liver transplantation. The authors report that the 10-year post-transplant survival and recurrence rates were 61.5% and 13.3%, respectively, in those always within the Milan criteria, 52.1% and 20.6% among those whose disease was downstaged, and 43.3% and 41.1% in those whose disease was never downstaged. Characteristics that predicted recurrence after downstaging were tumor size > 7 cm at diagnosis (odds ratio [OR] 2.62; 95% CI 1.20-5.75; P = .02), more than three tumors at diagnosis (OR 2.34; 95% CI 1.22-4.50; P = .01), and alpha-fetoprotein (AFP) response ≥ 20 ng/mL with < 50% improvement from maximum AFP before transplantation (OR 1.99; 95% CI 1.14-3.46; P = .02). Additionally, patients with recurrent tumors that were surgically resected had improved 5-year post-recurrence survival (31.6% vs 7.3%; P < .001). The conclusion was that the national downstaging policies were valid and should continue.

For patients who have unresectable HCC, systemic therapy is the mainstay of treatment. Peng and colleagues reported the results of the LAUNCH phase 3 clinical trial that randomized patients to receive lenvatinib alone or lenvatinib plus transarterial chemoembolization (TACE). Out of 338 patients, 170 received lenvatinib plus TACE. Unsurprisingly, the response rate was higher with the combination (54.1% vs 25.0%; P < .001); however, so was the median overall survival (17.8 vs 11.5 months; hazard ratio 0.45; P < .001), and median progression-free survival (10.6 vs 6.4 months; hazard ratio 0.43; P < .001). The investigators concluded that the addition of TACE to lenvatinib had manageable toxicities, improved clinical outcomes, and could be used as a potential first-line treatment for some patients with unresectable HCC.

Finally, in patients whose HCC progressed after a single TACE treatment, the question remains whether repeated TACE is worthwhile. Zhao and colleagues retrospectively reviewed the outcomes of 94 patients who underwent at least one TACE. Of these, 28 (29.8%) had a response to the first TACE, and these patients tended to have a longer OS compared with nonresponders (36.7 vs 21.5 months; P = .071). Of the 43 initial nonresponders who underwent a second TACE, 15 of 43 (34.9%) achieved a response and had an improved median overall survival (47.8 v. 13.6 months; P = .01), suggesting that repeat TACE may offer a benefit to some patients, even after no response to the initial treatment.

Liver transplantation has the opportunity to cure both localized HCC as well as underlying liver cirrhosis. Donor organ shortage has led to the implementation of the Milan criteria as a way to identify patients whose tumor burden is low enough to predict a good outcome. Downstaging liver cancer to fit within Milan criteria has been controversial.

Tabrizian and colleagues undertook a retrospective cohort analysis of 2645 adult patients with HCC who underwent liver transplant. Out of those, 2122 patients always had disease that was within the Milan criteria, 341 patients had HCC that was downstaged to fit within the Milan criteria, and 182 patients had HCC that was outside the Milan criteria at the time of liver transplantation. The authors report that the 10-year post-transplant survival and recurrence rates were 61.5% and 13.3%, respectively, in those always within the Milan criteria, 52.1% and 20.6% among those whose disease was downstaged, and 43.3% and 41.1% in those whose disease was never downstaged. Characteristics that predicted recurrence after downstaging were tumor size > 7 cm at diagnosis (odds ratio [OR] 2.62; 95% CI 1.20-5.75; P = .02), more than three tumors at diagnosis (OR 2.34; 95% CI 1.22-4.50; P = .01), and alpha-fetoprotein (AFP) response ≥ 20 ng/mL with < 50% improvement from maximum AFP before transplantation (OR 1.99; 95% CI 1.14-3.46; P = .02). Additionally, patients with recurrent tumors that were surgically resected had improved 5-year post-recurrence survival (31.6% vs 7.3%; P < .001). The conclusion was that the national downstaging policies were valid and should continue.

For patients who have unresectable HCC, systemic therapy is the mainstay of treatment. Peng and colleagues reported the results of the LAUNCH phase 3 clinical trial that randomized patients to receive lenvatinib alone or lenvatinib plus transarterial chemoembolization (TACE). Out of 338 patients, 170 received lenvatinib plus TACE. Unsurprisingly, the response rate was higher with the combination (54.1% vs 25.0%; P < .001); however, so was the median overall survival (17.8 vs 11.5 months; hazard ratio 0.45; P < .001), and median progression-free survival (10.6 vs 6.4 months; hazard ratio 0.43; P < .001). The investigators concluded that the addition of TACE to lenvatinib had manageable toxicities, improved clinical outcomes, and could be used as a potential first-line treatment for some patients with unresectable HCC.

Finally, in patients whose HCC progressed after a single TACE treatment, the question remains whether repeated TACE is worthwhile. Zhao and colleagues retrospectively reviewed the outcomes of 94 patients who underwent at least one TACE. Of these, 28 (29.8%) had a response to the first TACE, and these patients tended to have a longer OS compared with nonresponders (36.7 vs 21.5 months; P = .071). Of the 43 initial nonresponders who underwent a second TACE, 15 of 43 (34.9%) achieved a response and had an improved median overall survival (47.8 v. 13.6 months; P = .01), suggesting that repeat TACE may offer a benefit to some patients, even after no response to the initial treatment.

Liver transplantation has the opportunity to cure both localized HCC as well as underlying liver cirrhosis. Donor organ shortage has led to the implementation of the Milan criteria as a way to identify patients whose tumor burden is low enough to predict a good outcome. Downstaging liver cancer to fit within Milan criteria has been controversial.

Tabrizian and colleagues undertook a retrospective cohort analysis of 2645 adult patients with HCC who underwent liver transplant. Out of those, 2122 patients always had disease that was within the Milan criteria, 341 patients had HCC that was downstaged to fit within the Milan criteria, and 182 patients had HCC that was outside the Milan criteria at the time of liver transplantation. The authors report that the 10-year post-transplant survival and recurrence rates were 61.5% and 13.3%, respectively, in those always within the Milan criteria, 52.1% and 20.6% among those whose disease was downstaged, and 43.3% and 41.1% in those whose disease was never downstaged. Characteristics that predicted recurrence after downstaging were tumor size > 7 cm at diagnosis (odds ratio [OR] 2.62; 95% CI 1.20-5.75; P = .02), more than three tumors at diagnosis (OR 2.34; 95% CI 1.22-4.50; P = .01), and alpha-fetoprotein (AFP) response ≥ 20 ng/mL with < 50% improvement from maximum AFP before transplantation (OR 1.99; 95% CI 1.14-3.46; P = .02). Additionally, patients with recurrent tumors that were surgically resected had improved 5-year post-recurrence survival (31.6% vs 7.3%; P < .001). The conclusion was that the national downstaging policies were valid and should continue.

For patients who have unresectable HCC, systemic therapy is the mainstay of treatment. Peng and colleagues reported the results of the LAUNCH phase 3 clinical trial that randomized patients to receive lenvatinib alone or lenvatinib plus transarterial chemoembolization (TACE). Out of 338 patients, 170 received lenvatinib plus TACE. Unsurprisingly, the response rate was higher with the combination (54.1% vs 25.0%; P < .001); however, so was the median overall survival (17.8 vs 11.5 months; hazard ratio 0.45; P < .001), and median progression-free survival (10.6 vs 6.4 months; hazard ratio 0.43; P < .001). The investigators concluded that the addition of TACE to lenvatinib had manageable toxicities, improved clinical outcomes, and could be used as a potential first-line treatment for some patients with unresectable HCC.

Finally, in patients whose HCC progressed after a single TACE treatment, the question remains whether repeated TACE is worthwhile. Zhao and colleagues retrospectively reviewed the outcomes of 94 patients who underwent at least one TACE. Of these, 28 (29.8%) had a response to the first TACE, and these patients tended to have a longer OS compared with nonresponders (36.7 vs 21.5 months; P = .071). Of the 43 initial nonresponders who underwent a second TACE, 15 of 43 (34.9%) achieved a response and had an improved median overall survival (47.8 v. 13.6 months; P = .01), suggesting that repeat TACE may offer a benefit to some patients, even after no response to the initial treatment.

Researchers in France have discovered monkeypox virus in anal samples of men with no symptoms of the disease, advancing the possibility that asymptomatic carriers may be hidden drivers of the global outbreak.

The findings, published in Annals of Internal Medicine, follow a similar, non–peer-reviewed report from Belgium. Researchers in both studies tested swabs for monkeypox in men who have sex with men. These swabs had been collected for routine STI screening.

It’s unclear whether asymptomatic individuals who test positive for monkeypox can spread the virus, the French team wrote. But if so, public health strategies to vaccinate those with known exposure “may not be sufficient to contain spread.”

In an editorial accompanying their paper, Stuart Isaacs, MD, associate professor at the University of Pennsylvania, Philadelphia, said it “raises the question of whether asymptomatic or subclinical infections are contributing to the current worldwide outbreak.”

Historically, transmission of monkeypox and its close relative, smallpox, was thought to be greatest when a rash was present, Dr. Isaacs wrote. “Long chains of human-to-human transmission were rare” with monkeypox.

That’s changed with the current outbreak, which was first detected in May. On Aug. 17, the World Health Organization reported more than 35,000 cases in 92 countries, with 12 deaths.
 

Research methods

For the French study, researchers conducted polymerase chain reaction tests on 200 anorectal swabs from asymptomatic individuals that had been collected from June 5 to July 11 in order to screen for gonorrhea and chlamydia. Of those, 13 (6.5%) were positive for monkeypox.

During the study period, STI testing had been suspended in individuals with monkeypox symptoms because of safety concerns, the researchers reported.

The research team contacted the 13 monkeypox-positive patients and advised them to limit sexual activity for 21 days following their test and notify recent sexual partners. None reported having developed symptoms, but two subsequently returned to the clinic with symptoms – one had an anal rash and the other a sore throat.

In the Belgian report, posted publicly on June 21 as a preprint, 3 of 224 anal samples collected for STI screening in May tested positive for monkeypox. All three of the men who tested positive said they did not have any symptoms in the weeks before and after the sample was taken.

At follow-up testing, 21-37 days after the initial samples were taken, all patients who had previously tested positive were negative. This was “likely as a consequence of spontaneous clearance of the infection,” the authors of that paper wrote.
 

Clinical implications of findings are uncertain

Monica Gandhi, MD, MPH, a professor of medicine at the University of California, San Francisco, said in an interview that the clinical implications of the findings are uncertain because it’s not known how much viral transmission results from asymptomatic individuals.

Nevertheless, Dr. Gandhi said that “vaccinating all gay men for monkeypox who will accept the vaccine is prudent,” compared with a less aggressive strategy of only vaccinating those with known exposure, which is called ring vaccination. That way, “we can be assured to provide immunity to large swaths of the at-risk population.”

Dr. Gandhi said that movement toward mass vaccination of gay men is occurring in the United States, Canada, Europe, and Australia, despite limited vaccine supply.

She added that, although monkeypox has been concentrated in communities of men who have sex with men, “anyone with multiple sexual partners should be vaccinated given the data.”

However, a WHO official recently cautioned that reports of breakthrough infections in individuals who were vaccinated against monkeypox constitute a reminder that “vaccine is not a silver bullet.”
 

Non-vaccine interventions are also needed

Other experts stressed the need for nonvaccine interventions.

In his editorial, Dr. Isaacs said an “expanded” ring vaccination strategy in communities of high risk is likely needed, but ultimately the outbreak will only be controlled if vaccination is accompanied by other measures such as identifying and isolating cases, making treatment available, and educating individuals about how to reduce their risk.

Aileen Marty, MD, a professor of infectious diseases at Florida International University, Miami, said in an interview that the new evidence makes it “incredibly important” to inform people that they might be infected by a sex partner even if that person does not have telltale lesions.

Dr. Marty said she has been advising men who have sex with men to “reduce or eliminate situations in which they find themselves with multiple anonymous individuals.”

Although most individuals recover from monkeypox, the disease can lead to hospitalization, disfigurement, blindness, and even death, Dr. Marty noted, adding that monkeypox is “absolutely a disease to avoid.”

Authors of the French study reported financial relationships with Gilead Sciences, Viiv Healthcare, MSD, AstraZeneca, Theratechnologies, Janssen Pharmaceuticals, Pfizer, GlaxoSmithKline, and bioMérieux. Dr. Isaacs reported grants from the Department of Veterans Affairs and the National Institutes of Health and royalties from UpToDate. Dr. Gandhi and Dr. Marty reported no relevant financial interests.

Researchers in France have discovered monkeypox virus in anal samples of men with no symptoms of the disease, advancing the possibility that asymptomatic carriers may be hidden drivers of the global outbreak.

The findings, published in Annals of Internal Medicine, follow a similar, non–peer-reviewed report from Belgium. Researchers in both studies tested swabs for monkeypox in men who have sex with men. These swabs had been collected for routine STI screening.

It’s unclear whether asymptomatic individuals who test positive for monkeypox can spread the virus, the French team wrote. But if so, public health strategies to vaccinate those with known exposure “may not be sufficient to contain spread.”

In an editorial accompanying their paper, Stuart Isaacs, MD, associate professor at the University of Pennsylvania, Philadelphia, said it “raises the question of whether asymptomatic or subclinical infections are contributing to the current worldwide outbreak.”

Historically, transmission of monkeypox and its close relative, smallpox, was thought to be greatest when a rash was present, Dr. Isaacs wrote. “Long chains of human-to-human transmission were rare” with monkeypox.

That’s changed with the current outbreak, which was first detected in May. On Aug. 17, the World Health Organization reported more than 35,000 cases in 92 countries, with 12 deaths.
 

Research methods

For the French study, researchers conducted polymerase chain reaction tests on 200 anorectal swabs from asymptomatic individuals that had been collected from June 5 to July 11 in order to screen for gonorrhea and chlamydia. Of those, 13 (6.5%) were positive for monkeypox.

During the study period, STI testing had been suspended in individuals with monkeypox symptoms because of safety concerns, the researchers reported.

The research team contacted the 13 monkeypox-positive patients and advised them to limit sexual activity for 21 days following their test and notify recent sexual partners. None reported having developed symptoms, but two subsequently returned to the clinic with symptoms – one had an anal rash and the other a sore throat.

In the Belgian report, posted publicly on June 21 as a preprint, 3 of 224 anal samples collected for STI screening in May tested positive for monkeypox. All three of the men who tested positive said they did not have any symptoms in the weeks before and after the sample was taken.

At follow-up testing, 21-37 days after the initial samples were taken, all patients who had previously tested positive were negative. This was “likely as a consequence of spontaneous clearance of the infection,” the authors of that paper wrote.
 

Clinical implications of findings are uncertain

Monica Gandhi, MD, MPH, a professor of medicine at the University of California, San Francisco, said in an interview that the clinical implications of the findings are uncertain because it’s not known how much viral transmission results from asymptomatic individuals.

Nevertheless, Dr. Gandhi said that “vaccinating all gay men for monkeypox who will accept the vaccine is prudent,” compared with a less aggressive strategy of only vaccinating those with known exposure, which is called ring vaccination. That way, “we can be assured to provide immunity to large swaths of the at-risk population.”

Dr. Gandhi said that movement toward mass vaccination of gay men is occurring in the United States, Canada, Europe, and Australia, despite limited vaccine supply.

She added that, although monkeypox has been concentrated in communities of men who have sex with men, “anyone with multiple sexual partners should be vaccinated given the data.”

However, a WHO official recently cautioned that reports of breakthrough infections in individuals who were vaccinated against monkeypox constitute a reminder that “vaccine is not a silver bullet.”
 

Non-vaccine interventions are also needed

Other experts stressed the need for nonvaccine interventions.

In his editorial, Dr. Isaacs said an “expanded” ring vaccination strategy in communities of high risk is likely needed, but ultimately the outbreak will only be controlled if vaccination is accompanied by other measures such as identifying and isolating cases, making treatment available, and educating individuals about how to reduce their risk.

Aileen Marty, MD, a professor of infectious diseases at Florida International University, Miami, said in an interview that the new evidence makes it “incredibly important” to inform people that they might be infected by a sex partner even if that person does not have telltale lesions.

Dr. Marty said she has been advising men who have sex with men to “reduce or eliminate situations in which they find themselves with multiple anonymous individuals.”

Although most individuals recover from monkeypox, the disease can lead to hospitalization, disfigurement, blindness, and even death, Dr. Marty noted, adding that monkeypox is “absolutely a disease to avoid.”

Authors of the French study reported financial relationships with Gilead Sciences, Viiv Healthcare, MSD, AstraZeneca, Theratechnologies, Janssen Pharmaceuticals, Pfizer, GlaxoSmithKline, and bioMérieux. Dr. Isaacs reported grants from the Department of Veterans Affairs and the National Institutes of Health and royalties from UpToDate. Dr. Gandhi and Dr. Marty reported no relevant financial interests.

Researchers in France have discovered monkeypox virus in anal samples of men with no symptoms of the disease, advancing the possibility that asymptomatic carriers may be hidden drivers of the global outbreak.

The findings, published in Annals of Internal Medicine, follow a similar, non–peer-reviewed report from Belgium. Researchers in both studies tested swabs for monkeypox in men who have sex with men. These swabs had been collected for routine STI screening.

It’s unclear whether asymptomatic individuals who test positive for monkeypox can spread the virus, the French team wrote. But if so, public health strategies to vaccinate those with known exposure “may not be sufficient to contain spread.”

In an editorial accompanying their paper, Stuart Isaacs, MD, associate professor at the University of Pennsylvania, Philadelphia, said it “raises the question of whether asymptomatic or subclinical infections are contributing to the current worldwide outbreak.”

Historically, transmission of monkeypox and its close relative, smallpox, was thought to be greatest when a rash was present, Dr. Isaacs wrote. “Long chains of human-to-human transmission were rare” with monkeypox.

That’s changed with the current outbreak, which was first detected in May. On Aug. 17, the World Health Organization reported more than 35,000 cases in 92 countries, with 12 deaths.
 

Research methods

For the French study, researchers conducted polymerase chain reaction tests on 200 anorectal swabs from asymptomatic individuals that had been collected from June 5 to July 11 in order to screen for gonorrhea and chlamydia. Of those, 13 (6.5%) were positive for monkeypox.

During the study period, STI testing had been suspended in individuals with monkeypox symptoms because of safety concerns, the researchers reported.

The research team contacted the 13 monkeypox-positive patients and advised them to limit sexual activity for 21 days following their test and notify recent sexual partners. None reported having developed symptoms, but two subsequently returned to the clinic with symptoms – one had an anal rash and the other a sore throat.

In the Belgian report, posted publicly on June 21 as a preprint, 3 of 224 anal samples collected for STI screening in May tested positive for monkeypox. All three of the men who tested positive said they did not have any symptoms in the weeks before and after the sample was taken.

At follow-up testing, 21-37 days after the initial samples were taken, all patients who had previously tested positive were negative. This was “likely as a consequence of spontaneous clearance of the infection,” the authors of that paper wrote.
 

Clinical implications of findings are uncertain

Monica Gandhi, MD, MPH, a professor of medicine at the University of California, San Francisco, said in an interview that the clinical implications of the findings are uncertain because it’s not known how much viral transmission results from asymptomatic individuals.

Nevertheless, Dr. Gandhi said that “vaccinating all gay men for monkeypox who will accept the vaccine is prudent,” compared with a less aggressive strategy of only vaccinating those with known exposure, which is called ring vaccination. That way, “we can be assured to provide immunity to large swaths of the at-risk population.”

Dr. Gandhi said that movement toward mass vaccination of gay men is occurring in the United States, Canada, Europe, and Australia, despite limited vaccine supply.

She added that, although monkeypox has been concentrated in communities of men who have sex with men, “anyone with multiple sexual partners should be vaccinated given the data.”

However, a WHO official recently cautioned that reports of breakthrough infections in individuals who were vaccinated against monkeypox constitute a reminder that “vaccine is not a silver bullet.”
 

Non-vaccine interventions are also needed

Other experts stressed the need for nonvaccine interventions.

In his editorial, Dr. Isaacs said an “expanded” ring vaccination strategy in communities of high risk is likely needed, but ultimately the outbreak will only be controlled if vaccination is accompanied by other measures such as identifying and isolating cases, making treatment available, and educating individuals about how to reduce their risk.

Aileen Marty, MD, a professor of infectious diseases at Florida International University, Miami, said in an interview that the new evidence makes it “incredibly important” to inform people that they might be infected by a sex partner even if that person does not have telltale lesions.

Dr. Marty said she has been advising men who have sex with men to “reduce or eliminate situations in which they find themselves with multiple anonymous individuals.”

Although most individuals recover from monkeypox, the disease can lead to hospitalization, disfigurement, blindness, and even death, Dr. Marty noted, adding that monkeypox is “absolutely a disease to avoid.”

Authors of the French study reported financial relationships with Gilead Sciences, Viiv Healthcare, MSD, AstraZeneca, Theratechnologies, Janssen Pharmaceuticals, Pfizer, GlaxoSmithKline, and bioMérieux. Dr. Isaacs reported grants from the Department of Veterans Affairs and the National Institutes of Health and royalties from UpToDate. Dr. Gandhi and Dr. Marty reported no relevant financial interests.

Polyneuropathy (PNP) remains a common comorbidity among patients with chronic obstructive pulmonary disease (COPD), and better screening strategies are needed to identify the condition and improve patients’ quality of life, according to authors of a recent review.

“Recent advances demonstrate that the relationship between COPD and the nervous system is extensive, and patients are at increased risk of stroke, dementia, depression, and other neurological and psychiatric conditions, even after controlling for the main confounding risk factors, such as age and smoking,” write Irina Odajiu, MD, of Colentina Clinical Hospital, Bucharest, Romania, and colleagues. However, data on the relationship between COPD and peripheral nervous system pathology are limited.

PNP is distinct from peripheral neuropathy and neuropathy, the researchers emphasize.

“Polyneuropathy implies a homogeneous process affecting peripheral nerves, specifically distal nerves, more severely than proximal ones,” while peripheral neuropathy refers to any disorder of the peripheral nervous system, they explain.

In an article published in Respiratory Medicine, the authors summarize the latest data on the association between COPD and polyneuropathy. They reviewed data from 21 studies published between 1981 and 2021. All studies included adults with COPD. The mean age of the patients was 55-65 years.

Peripheral neuropathy represents a significant comorbidity among patients with COPD. The percentage of cases of peripheral neuropathy among patients in the study populations ranged from 15% to 93.8%. Of these cases, the majority were of axonal sensory polyneuropathy. In most of the studies, the neuropathy affected the lower limbs more than the upper limbs.

“Additionally, in most presented studies, peripheral neuropathy correlated with disease duration and hypoxemia severity; the longer the duration and the more severe hypoxia, the more severe peripheral neuropathy was,” the researchers note.

Overall, potential predisposing factors for PNP among patients with COPD (in addition to chronic hypoxemia) included older age, poor nutrition, systemic inflammation, COPD medications, smoking, and increased partial pressure of carbon dioxide (hypercapnia).

Several strategies for managing peripheral neuropathy for patients with COPD were described. Prophylaxis options include neuroprotection with hormones such as progesterone, neuronal growth factors, and corticosteroids, although none have shown high levels of effectiveness, the researchers write. Topical treatment with muscarinic antagonists has shown some potential and may be a practical therapeutic choice, they say. Oxygen support, including hyperbaric oxygen therapy, has demonstrated healing of diabetic leg ulcers associated with PNP and has led to improvements in pain-related symptoms and quality-of-life scores, they add.

Although PNP is often present in patients with COPD, no association between COPD severity and PNP has been determined, the researchers write in their discussion section.

“Moreover, the current data do not indicate a relationship between COPD stages, GOLD classification, or degree of obstruction and PNP,” they say.

The data support screening of all COPD patients for PNP, both clinically and with electrodiagnostic studies, despite the absence of current specific COPD-related PNP screening tools, they write.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

Polyneuropathy (PNP) remains a common comorbidity among patients with chronic obstructive pulmonary disease (COPD), and better screening strategies are needed to identify the condition and improve patients’ quality of life, according to authors of a recent review.

“Recent advances demonstrate that the relationship between COPD and the nervous system is extensive, and patients are at increased risk of stroke, dementia, depression, and other neurological and psychiatric conditions, even after controlling for the main confounding risk factors, such as age and smoking,” write Irina Odajiu, MD, of Colentina Clinical Hospital, Bucharest, Romania, and colleagues. However, data on the relationship between COPD and peripheral nervous system pathology are limited.

PNP is distinct from peripheral neuropathy and neuropathy, the researchers emphasize.

“Polyneuropathy implies a homogeneous process affecting peripheral nerves, specifically distal nerves, more severely than proximal ones,” while peripheral neuropathy refers to any disorder of the peripheral nervous system, they explain.

In an article published in Respiratory Medicine, the authors summarize the latest data on the association between COPD and polyneuropathy. They reviewed data from 21 studies published between 1981 and 2021. All studies included adults with COPD. The mean age of the patients was 55-65 years.

Peripheral neuropathy represents a significant comorbidity among patients with COPD. The percentage of cases of peripheral neuropathy among patients in the study populations ranged from 15% to 93.8%. Of these cases, the majority were of axonal sensory polyneuropathy. In most of the studies, the neuropathy affected the lower limbs more than the upper limbs.

“Additionally, in most presented studies, peripheral neuropathy correlated with disease duration and hypoxemia severity; the longer the duration and the more severe hypoxia, the more severe peripheral neuropathy was,” the researchers note.

Overall, potential predisposing factors for PNP among patients with COPD (in addition to chronic hypoxemia) included older age, poor nutrition, systemic inflammation, COPD medications, smoking, and increased partial pressure of carbon dioxide (hypercapnia).

Several strategies for managing peripheral neuropathy for patients with COPD were described. Prophylaxis options include neuroprotection with hormones such as progesterone, neuronal growth factors, and corticosteroids, although none have shown high levels of effectiveness, the researchers write. Topical treatment with muscarinic antagonists has shown some potential and may be a practical therapeutic choice, they say. Oxygen support, including hyperbaric oxygen therapy, has demonstrated healing of diabetic leg ulcers associated with PNP and has led to improvements in pain-related symptoms and quality-of-life scores, they add.

Although PNP is often present in patients with COPD, no association between COPD severity and PNP has been determined, the researchers write in their discussion section.

“Moreover, the current data do not indicate a relationship between COPD stages, GOLD classification, or degree of obstruction and PNP,” they say.

The data support screening of all COPD patients for PNP, both clinically and with electrodiagnostic studies, despite the absence of current specific COPD-related PNP screening tools, they write.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

Polyneuropathy (PNP) remains a common comorbidity among patients with chronic obstructive pulmonary disease (COPD), and better screening strategies are needed to identify the condition and improve patients’ quality of life, according to authors of a recent review.

“Recent advances demonstrate that the relationship between COPD and the nervous system is extensive, and patients are at increased risk of stroke, dementia, depression, and other neurological and psychiatric conditions, even after controlling for the main confounding risk factors, such as age and smoking,” write Irina Odajiu, MD, of Colentina Clinical Hospital, Bucharest, Romania, and colleagues. However, data on the relationship between COPD and peripheral nervous system pathology are limited.

PNP is distinct from peripheral neuropathy and neuropathy, the researchers emphasize.

“Polyneuropathy implies a homogeneous process affecting peripheral nerves, specifically distal nerves, more severely than proximal ones,” while peripheral neuropathy refers to any disorder of the peripheral nervous system, they explain.

In an article published in Respiratory Medicine, the authors summarize the latest data on the association between COPD and polyneuropathy. They reviewed data from 21 studies published between 1981 and 2021. All studies included adults with COPD. The mean age of the patients was 55-65 years.

Peripheral neuropathy represents a significant comorbidity among patients with COPD. The percentage of cases of peripheral neuropathy among patients in the study populations ranged from 15% to 93.8%. Of these cases, the majority were of axonal sensory polyneuropathy. In most of the studies, the neuropathy affected the lower limbs more than the upper limbs.

“Additionally, in most presented studies, peripheral neuropathy correlated with disease duration and hypoxemia severity; the longer the duration and the more severe hypoxia, the more severe peripheral neuropathy was,” the researchers note.

Overall, potential predisposing factors for PNP among patients with COPD (in addition to chronic hypoxemia) included older age, poor nutrition, systemic inflammation, COPD medications, smoking, and increased partial pressure of carbon dioxide (hypercapnia).

Several strategies for managing peripheral neuropathy for patients with COPD were described. Prophylaxis options include neuroprotection with hormones such as progesterone, neuronal growth factors, and corticosteroids, although none have shown high levels of effectiveness, the researchers write. Topical treatment with muscarinic antagonists has shown some potential and may be a practical therapeutic choice, they say. Oxygen support, including hyperbaric oxygen therapy, has demonstrated healing of diabetic leg ulcers associated with PNP and has led to improvements in pain-related symptoms and quality-of-life scores, they add.

Although PNP is often present in patients with COPD, no association between COPD severity and PNP has been determined, the researchers write in their discussion section.

“Moreover, the current data do not indicate a relationship between COPD stages, GOLD classification, or degree of obstruction and PNP,” they say.

The data support screening of all COPD patients for PNP, both clinically and with electrodiagnostic studies, despite the absence of current specific COPD-related PNP screening tools, they write.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

PORTLAND, ORE. – When patients present to Brandon L. Adler, MD, with dermatitis on the eyelid, face, or neck, he routinely asks them if they apply essential oils on their skin, or if they have an essential oil diffuser or nebulizer in their home.

“The answer is frequently ‘yes,’ ” Dr. Adler, clinical assistant professor of dermatology at the University of Southern California, Los Angeles, said at the annual meeting of the Pacific Dermatologic Association. “Essential oils are widely used throughout the wellness industry. They are contained in personal care products, beauty products, natural cleaning products, and they’re being diffused by our patients into the air. More than 75 essential oils are reported to cause allergic contact dermatitis.”

yangna/iStock/Getty Images

Natural chemical components contained in essential oils can cause skin reactions, especially linalool and limonene. “Linalool is most classically associated with lavender, while limonene is associated with citrus, but they’re found in many different plants,” said Dr. Adler, who directs USC’s contact dermatitis clinic. “On their own, linalool and limonene are not particularly allergenic; they’re not a big deal in the patch test clinic. The problem comes when we add air to the mix, because they oxidize to hydroperoxides of linalool and limonene. These are quite potent allergens.”

According to the most recent North American Contact Dermatitis Group data, 8.9% of patients undergoing patch testing tested positive to linalool hydroperoxides and 2.6% were positive to limonene hydroperoxides.

Dr. Adler discussed the case of a female massage therapist who presented with refractory hand dermatitis and was on methotrexate and dupilumab at the time of consultation but was still symptomatic. She patch-tested positive to limonene and linalool hydroperoxides as well as multiple essential oils that she had been using with her clients, ranging from sacred frankincense oil to basil oil, and she was advised to massage using only coconut or vegetable oils.

Essential oil allergy may also be related to cannabis allergy. According to Dr. Adler, allergic contact dermatitis to cannabis has been rarely reported, but in an analysis of 103 commercial topical cannabinoid preparations that he published with Vincent DeLeo, MD, also with USC, 84% contained a NACDG allergen, frequently essential oils.

More recently, Dr. Adler and colleagues reported the case of a 40-year-old woman who was referred for patch testing for nummular dermatitis that wasn’t responding to treatment. The patient was found to be using topical cannabis and also grew cannabis at home. “She asked to be patch-tested to her homegrown cannabis and had a strong positive patch test to the cannabis, linalool and limonene hydroperoxides, and other essential oils,” Dr. Adler recalled. “We sent her cannabis sample for analysis at a commercial lab and found that it contained limonene and other allergenic terpene chemicals.

“We’re just starting to unravel what this means in terms of our patients and how to manage them, but many are using topical cannabis and topical CBD. I suspect this is a lot less rare than we realize.”

Another recent case from Europe reported allergic contact dermatitis to Cannabis sativa (hemp) seed oil following topical application, with positive patch testing.

Dr. Adler disclosed that he has received research grants from the American Contact Dermatitis Society. He is also an investigator for AbbVie and a consultant for the Skin Research Institute.

PORTLAND, ORE. – When patients present to Brandon L. Adler, MD, with dermatitis on the eyelid, face, or neck, he routinely asks them if they apply essential oils on their skin, or if they have an essential oil diffuser or nebulizer in their home.

“The answer is frequently ‘yes,’ ” Dr. Adler, clinical assistant professor of dermatology at the University of Southern California, Los Angeles, said at the annual meeting of the Pacific Dermatologic Association. “Essential oils are widely used throughout the wellness industry. They are contained in personal care products, beauty products, natural cleaning products, and they’re being diffused by our patients into the air. More than 75 essential oils are reported to cause allergic contact dermatitis.”

yangna/iStock/Getty Images

Natural chemical components contained in essential oils can cause skin reactions, especially linalool and limonene. “Linalool is most classically associated with lavender, while limonene is associated with citrus, but they’re found in many different plants,” said Dr. Adler, who directs USC’s contact dermatitis clinic. “On their own, linalool and limonene are not particularly allergenic; they’re not a big deal in the patch test clinic. The problem comes when we add air to the mix, because they oxidize to hydroperoxides of linalool and limonene. These are quite potent allergens.”

According to the most recent North American Contact Dermatitis Group data, 8.9% of patients undergoing patch testing tested positive to linalool hydroperoxides and 2.6% were positive to limonene hydroperoxides.

Dr. Adler discussed the case of a female massage therapist who presented with refractory hand dermatitis and was on methotrexate and dupilumab at the time of consultation but was still symptomatic. She patch-tested positive to limonene and linalool hydroperoxides as well as multiple essential oils that she had been using with her clients, ranging from sacred frankincense oil to basil oil, and she was advised to massage using only coconut or vegetable oils.

Essential oil allergy may also be related to cannabis allergy. According to Dr. Adler, allergic contact dermatitis to cannabis has been rarely reported, but in an analysis of 103 commercial topical cannabinoid preparations that he published with Vincent DeLeo, MD, also with USC, 84% contained a NACDG allergen, frequently essential oils.

More recently, Dr. Adler and colleagues reported the case of a 40-year-old woman who was referred for patch testing for nummular dermatitis that wasn’t responding to treatment. The patient was found to be using topical cannabis and also grew cannabis at home. “She asked to be patch-tested to her homegrown cannabis and had a strong positive patch test to the cannabis, linalool and limonene hydroperoxides, and other essential oils,” Dr. Adler recalled. “We sent her cannabis sample for analysis at a commercial lab and found that it contained limonene and other allergenic terpene chemicals.

“We’re just starting to unravel what this means in terms of our patients and how to manage them, but many are using topical cannabis and topical CBD. I suspect this is a lot less rare than we realize.”

Another recent case from Europe reported allergic contact dermatitis to Cannabis sativa (hemp) seed oil following topical application, with positive patch testing.

Dr. Adler disclosed that he has received research grants from the American Contact Dermatitis Society. He is also an investigator for AbbVie and a consultant for the Skin Research Institute.

PORTLAND, ORE. – When patients present to Brandon L. Adler, MD, with dermatitis on the eyelid, face, or neck, he routinely asks them if they apply essential oils on their skin, or if they have an essential oil diffuser or nebulizer in their home.

“The answer is frequently ‘yes,’ ” Dr. Adler, clinical assistant professor of dermatology at the University of Southern California, Los Angeles, said at the annual meeting of the Pacific Dermatologic Association. “Essential oils are widely used throughout the wellness industry. They are contained in personal care products, beauty products, natural cleaning products, and they’re being diffused by our patients into the air. More than 75 essential oils are reported to cause allergic contact dermatitis.”

yangna/iStock/Getty Images

Natural chemical components contained in essential oils can cause skin reactions, especially linalool and limonene. “Linalool is most classically associated with lavender, while limonene is associated with citrus, but they’re found in many different plants,” said Dr. Adler, who directs USC’s contact dermatitis clinic. “On their own, linalool and limonene are not particularly allergenic; they’re not a big deal in the patch test clinic. The problem comes when we add air to the mix, because they oxidize to hydroperoxides of linalool and limonene. These are quite potent allergens.”

According to the most recent North American Contact Dermatitis Group data, 8.9% of patients undergoing patch testing tested positive to linalool hydroperoxides and 2.6% were positive to limonene hydroperoxides.

Dr. Adler discussed the case of a female massage therapist who presented with refractory hand dermatitis and was on methotrexate and dupilumab at the time of consultation but was still symptomatic. She patch-tested positive to limonene and linalool hydroperoxides as well as multiple essential oils that she had been using with her clients, ranging from sacred frankincense oil to basil oil, and she was advised to massage using only coconut or vegetable oils.

Essential oil allergy may also be related to cannabis allergy. According to Dr. Adler, allergic contact dermatitis to cannabis has been rarely reported, but in an analysis of 103 commercial topical cannabinoid preparations that he published with Vincent DeLeo, MD, also with USC, 84% contained a NACDG allergen, frequently essential oils.

More recently, Dr. Adler and colleagues reported the case of a 40-year-old woman who was referred for patch testing for nummular dermatitis that wasn’t responding to treatment. The patient was found to be using topical cannabis and also grew cannabis at home. “She asked to be patch-tested to her homegrown cannabis and had a strong positive patch test to the cannabis, linalool and limonene hydroperoxides, and other essential oils,” Dr. Adler recalled. “We sent her cannabis sample for analysis at a commercial lab and found that it contained limonene and other allergenic terpene chemicals.

“We’re just starting to unravel what this means in terms of our patients and how to manage them, but many are using topical cannabis and topical CBD. I suspect this is a lot less rare than we realize.”

Another recent case from Europe reported allergic contact dermatitis to Cannabis sativa (hemp) seed oil following topical application, with positive patch testing.

Dr. Adler disclosed that he has received research grants from the American Contact Dermatitis Society. He is also an investigator for AbbVie and a consultant for the Skin Research Institute.